Current Medical Diagnosis and Treatment 2007 – 46th Edition II pdf

AccessMedicine - Print


Print Close Window
Note: Large images and tables on this page may necessitate printing in landscape mode.

Copyright ©2006 The McGraw-Hill Companies. All rights reserved.

Current Medical Dx & Tx > Infectious Diseases: General Problems >

Infectious Diseases: Introduction
Most infections are confined to specific organ systems, and many of the important infectious disease pathogens
are discussed in chapters dealing with the relevant anatomic areas. This chapter discusses some important
general problems related to infectious diseases.
Fever of Unknown Origin (FUO)
Essentials of Diagnosis
● Illness of at least 3 weeks duration.
● Fever over 38.3 °C on several occasions.
● Diagnosis has not been made after three outpatient visits or 3 days of hospitalization.
General Considerations
The intervals specified in the criteria for the diagnosis of FUO are arbitrary ones intended to exclude patients with
protracted but self-limited viral illnesses and to allow time for the usual radiographic, serologic, and cultural studies
to be performed. Because of costs of hospitalization and the availability of most screening tests on an outpatient
basis, the original criterion requiring 1 week of hospitalization has been modified to accept patients in whom a
diagnosis has not been made after three outpatient visits or 3 days of hospitalization.
Several additional categories of FUO have been added: (1) Nosocomial FUO refers to the hospitalized patient with
fever of 38.3 °C or higher on several occasions, due to a process not present or incubating at the time of admission,
in whom initial cultures are negative and the diagnosis remains unknown after 3 days of investigation (see
Nosocomial Infections, below). (2) Neutropenic FUO includes patients with fever of 38.3 °C or higher on several
occasions with less than 500 neutrophils per microliter in whom initial cultures are negative and the diagnosis
remains uncertain after 3 days (see Common Symptoms and Infections in the Immunocompromised Patient, below).

(3) HIV-associated FUO pertains to HIV-positive patients with fever of 38.3 °C or higher who have been febrile for 4
weeks or more as an outpatient or 3 days as an inpatient, in whom the diagnosis remains uncertain after 3 days of
investigation with at least 2 days for cultures to incubate (see Infectious Diseases: HIV). Although not usually
considered separately, FUO in solid organ transplant recipients is a common scenario with a unique differential
diagnosis and is discussed below.
For a general discussion of fever, see the section on fever and hyperthermia in Common Symptoms.
Common Causes
Most cases represent unusual manifestations of common diseases and not rare or exotic diseases—eg, tuberculosis,
endocarditis, gallbladder disease, and HIV (primary infection or opportunistic infection) are more common causes of
FUO than Whipple's disease or familial Mediterranean fever.
Age of Patient
In adults, infections (25–40% of cases) and cancer (25–40% of cases) account for the majority of FUOs. In children,
infections are the most common cause of FUO (30–50% of cases) and cancer a rare cause (5–10% of cases).
file:///C|/Documents%20and%20Settings/Adminis nfectious%20Diseases%20General%20Problems.htm (1 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
Autoimmune disorders occur with equal frequency in adults and children (10–20% of cases), but the diseases differ.
Juvenile rheumatoid arthritis is particularly common in children, whereas systemic lupus erythematosus, Wegener's
granulomatosis, and polyarteritis nodosa are more common in adults. Adult Still's disease, giant cell arteritis, and
polymyalgia rheumatica occur exclusively in adults. In the elderly (over 65 years of age), multisystem immune-
mediated diseases such as temporal arteritis, polymyalgia rheumatica, sarcoidosis, rheumatoid arthritis, and
Wegener's granulomatosis account for 25–30% of all FUOs.
Duration of Fever
The cause of FUO changes dramatically in patients who have been febrile for 6 months or longer. Infection, cancer,
and autoimmune disorders combined account for only 20% of FUOs in these patients. Instead, other entities such as
granulomatous diseases (granulomatous hepatitis, Crohn's disease, ulcerative colitis) and factitious fever become
important causes. One-fourth of patients who say they have been febrile for 6 months or longer actually have no
true fever or underlying disease. Instead, the usual normal circadian variation in temperature (temperature 0.5–1 °C
higher in the afternoon than in the morning) is interpreted as abnormal. Patients with episodic or recurrent fever (ie,
those who meet the criteria for FUO but have fever-free periods of 2 weeks or longer) are similar to those with
prolonged fever. Infection, malignancy, and autoimmune disorders account for only 20–25% of such fevers, whereas

various miscellaneous diseases (Crohn's disease, familial Mediterranean fever, allergic alveolitis) account for another
25%. Approximately 50% remain undiagnosed but have a benign course with eventual resolution of symptoms.
Immunologic Status
In the neutropenic patient, fungal infections and occult bacterial infection are important causes of FUO. In the
patient taking immunosuppressive medications (particularly organ transplant patients), cytomegalovirus (CMV)
infections are a frequent cause of fever, as are fungal infections, nocardiosis, Pneumocystis jiroveci (formerly
Pneumocystis carinii) pneumonia, and mycobacterial infections.
Classification of Causes of FUO
Most patients with FUO will fit into one of five categories.
Infection
Both systemic and localized infections can cause FUO. Tuberculosis and endocarditis are the most common systemic
infections, but mycoses, viral diseases (particularly infection with Epstein-Barr virus and CMV), toxoplasmosis,
brucellosis, Q fever, cat-scratch disease, salmonellosis, malaria, and many other less common infections have been
implicated. Primary infection with HIV or opportunistic infections associated with the AIDS—particularly
mycobacterial infections—can also present as FUO. The most common form of localized infection causing FUO is an
occult abscess. Liver, spleen, kidney, brain, and bone are organs in which abscess may be difficult to find. A
collection of pus may form in the peritoneal cavity or in the subdiaphragmatic, subhepatic, paracolic, or other areas.
Cholangitis, osteomyelitis, urinary tract infection, dental abscess, or paranasal sinusitis may cause prolonged fever.
Neoplasms
Many cancers can present as FUO. The most common are lymphoma (both Hodgkin's and non-Hodgkin's) and
leukemia. Other diseases of lymph nodes, such as angioimmunoblastic lymphoma and Castleman's disease, can also
cause FUO. Primary and metastatic tumors of the liver are frequently associated with fever, as are renal cell
carcinomas. Atrial myxoma is an often forgotten neoplasm that can result in fever. Chronic lymphocytic leukemia
and multiple myeloma are rarely associated with fever, and the presence of fever in patients with these diseases
should prompt a search for infection.
Autoimmune disorders
Still's disease, systemic lupus erythematosus, cryoglobulinemia, and polyarteritis nodosa are the most common
file:///C|/Documents%20and%20Settings/Adminis nfectious%20Diseases%20General%20Problems.htm (2 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
autoimmune causes of FUO. Giant cell arteritis and polymyalgia rheumatica are seen almost exclusively in patients

over 50 years of age and are nearly always associated with an elevated erythrocyte sedimentation rate (> 40 mm/h).
Miscellaneous causes
Many other conditions have been associated with FUO but less commonly than the foregoing types of illness.
Examples include thyroiditis, sarcoidosis, Whipple's disease, familial Mediterranean fever, recurrent pulmonary
emboli, alcoholic hepatitis, drug fever, and factitious fever.
Undiagnosed FUO
Despite extensive evaluation, the diagnosis remains elusive in 10–15% of patients. Of these patients, the fever
abates spontaneously in about 75% and the clinician never knows the cause; in the remainder, more classic
manifestations of the underlying disease appear over time.
Clinical Findings
Because the evaluation of a patient with FUO is costly and time-consuming, it is imperative to first document the
presence of fever. This is done by observing the patient while the temperature is being taken to ascertain that fever
is not factitious (self-induced). Associated findings that accompany fever include tachycardia, chills, and piloerection.
A thorough history—including family, occupational, social (sexual practices, use of injection drugs), dietary
(unpasteurized products, raw meat), exposures (animals, chemicals), and travel—may give clues to the diagnosis.
Repeated physical examination may reveal subtle, evanescent clinical findings essential to diagnosis.
Laboratory Tests
In addition to routine laboratory studies, blood cultures should always be obtained, preferably when the patient has
not taken antibiotics for several days, and should be held by the laboratory for 2 weeks to detect slow-growing
organisms. Cultures on special media are requested if Legionella, Bartonella, or nutritionally deficient streptococci
are considered possible pathogens. "Screening tests" with immunologic or microbiologic serologies ("febrile
agglutinins") are of low yield and should not be done. Specific serologic tests are helpful if the history or physical
examination suggests a specific diagnosis. A single elevated titer rarely allows one to make a diagnosis of infection;
instead, one must demonstrate a fourfold rise or fall in titer to confirm a specific infectious cause. Because infection
is the most common cause of FUO, other body fluids are usually cultured, ie, urine, sputum, stool, cerebrospinal
fluid, and morning gastric aspirates (if one suspects tuberculosis). Direct examination of blood smears may establish
a diagnosis of malaria or relapsing fever (Borrelia).
Imaging
All patients with FUO should have a chest radiograph. Studies such as sinus films, upper gastrointestinal series with
small bowel follow-through, barium enema, proctosigmoidoscopy, and evaluation of gallbladder function are

reserved for patients who have symptoms, signs, or a history that suggest disease in these body regions. CT scan of
the abdomen and pelvis is also frequently performed and is particularly useful for looking at the liver, spleen, and
retroperitoneum. When the CT scan is abnormal, the findings often lead to a specific diagnosis. A normal CT scan is
not quite as useful; more invasive procedures such as biopsy or exploratory laparotomy may be needed. The role of
MRI in the investigation of FUO has not been evaluated. In general, however, MRI is better than CT for detecting
lesions of the nervous system and is useful in diagnosing various vasculitides. Ultrasound is sensitive for detecting
lesions of the kidney, pancreas, and biliary tree. Echocardiography should be used if one is considering endocarditis
or atrial myxoma. Transesophageal echocardiography is more sensitive than surface echocardiography for detecting
valvular lesions, but even a negative transesophageal study does not exclude endocarditis (10% false-negative
rate). The usefulness of radionuclide studies in diagnosing FUO is variable. Theoretically, a gallium or positron-
emission (PET) scan would be more helpful than an indium-labeled white blood cell scan, because gallium and
file:///C|/Documents%20and%20Settings/Adminis nfectious%20Diseases%20General%20Problems.htm (3 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
fluorodeoxy-glucose may be useful for detecting infection, inflammation, and neoplasm whereas the indium scan is
useful only for detecting infection. Indium-labeled immunoglobulin may prove to be useful in detecting infection and
neoplasm and can be used in the neutropenic patient. It is not sensitive for lesions of the liver, kidney, and heart
because of high background activity. In general, radionuclide scans are plagued by high rates of false-positive and
false-negative results that are not useful when used as screening tests and, if done at all, are limited to those
patients whose history or examination suggests local inflammation or infection.
Biopsy
Invasive procedures are often required for diagnosis. Any abnormal finding should be aggressively evaluated:
Headache calls for lumbar puncture (see Figure: illustration) to rule out meningitis; skin from a rash should be
biopsied to look for cutaneous manifestations of collagen vascular disease or infection; and enlarged lymph nodes
should be aspirated or biopsied and examined for cytologic features to rule out neoplasm and sent for culture. Bone
marrow aspiration with biopsy is a relatively low-yield procedure (except in HIV-positive patients, in whom
mycobacterial infection is a common cause of FUO), but the risk is low and the procedure should be done if other
less invasive tests have not yielded a diagnosis. Liver biopsy will yield a specific diagnosis in 10–15% of patients
with FUO and should be considered in any patient with abnormal liver function tests even if the liver is normal in
size. The role of exploratory laparotomy is debatable since the advent of CT scanning and MRI. Laparotomy or
laparoscopy should be considered when the patient continues to deteriorate and the diagnosis is elusive despite

extensive evaluation.
Prepackaged disposable sterile tray for lumbar puncture. (Reproduced, with permission, from Chesnutt MS et
al: Office & Bedside Procedures. Originally published by Appleton & Lange. Copyright © 1992 by The McGraw-
Hill Companies, Inc.)
Treatment
Therapeutic trials are indicated if a diagnosis is strongly suspected—eg, it is reasonable to give antituberculous drugs
if tuberculosis is suspected, or tetracycline if brucellosis is suspected. However, if there is no clinical response in
several weeks, it is imperative to stop therapy and reevaluate the patient. In the seriously ill or rapidly deteriorating
file:///C|/Documents%20and%20Settings/Adminis nfectious%20Diseases%20General%20Problems.htm (4 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
patient, empiric therapy is often given. Antituberculosis medications (particularly in the elderly or foreign-born) and
broad-spectrum antibiotics are reasonable in this setting.
Empiric administration of corticosteroids should be discouraged; they can suppress fever if given in high enough
doses, but they can also exacerbate many infections, and infection remains a leading cause of FUO.
Crispin JC et al: Adult-onset Still disease as the cause of fever of unknown origin. Medicine (Baltimore) 2005;84:331.
[PMID: 16267408]

Knockaert DC et al: Fever of unknown origin in adults: 40 years on. J Intern Med 2003;253:263. [PMID: 12603493]

Mourad O et al: A comprehensive evidence-based approach to fever of unknown origin. Arch Intern Med
2003;163:545. [PMID: 12622601]

Ozaras R et al: Is laparotomy necessary in the diagnosis of fever of unknown origin? Acta Chir Belg 2005;105:89.
[PMID: 15790210]

Tal S et al: Fever of unknown origin in the elderly. J Intern Med 2002;242:295. [PMID: 12366602]

Vanderschueren S et al: From prolonged febrile illness to fever of unknown origin. Arch Intern Med 2003;163:1033.
[PMID: 12742800]

Woolery WA et al: Fever of unknown origin: keys to determining the etiology in older patients. Geriatrics
2004;59:41. [PMID: 15508555]

Infections in the Immunocompromised Patient
Essentials of Diagnosis
● Fever and other symptoms may be blunted because of immunosuppression; early diagnosis may be difficult.
● A contaminating organism in an immunocompetent individual may be a pathogen in an immunocompromised one.
● The interval since transplantation and the degree of immunosuppression can narrow the differential diagnosis.
● Empiric broad-spectrum antibiotics may be appropriate in high-risk patients whether or not symptoms are localized
because of high infection-related morbidity and mortality.
General Considerations
Immunocompromised patients have one or more defects in their natural defense mechanisms that put them at
an increased risk for infections. Not only is the risk of infection greater in these individuals, but once established it
is often severe, rapidly progressive, and life-threatening. Organisms that are not usually pathogens in
the immunocompetent person may cause life-threatening infection in the compromised patient (eg,
Staphylococcus epidermidis, Corynebacterium jeikeium, Propionibacterium acnes, Bacillus species). Therefore,
culture results must be interpreted with caution, and isolates should not be disregarded as merely
contaminants. Although the type of immunodeficiency is associated with specific infectious disease syndromes,
any pathogen can cause infection in any immunosuppressed patient at any time. Thus, a systematic evaluation
is required to identify a specific organism.
Impaired Humoral Immunity
Defects in humoral immunity are often congenital, although hypogammaglobulinemia can occur in multiple
myeloma, chronic lymphocytic leukemia, and in patients who have undergone splenectomy. Patients with
ineffective humoral immunity lack opsonizing antibodies and are at particular risk for infection with
encapsulated organisms, such as Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae.
file:///C|/Documents%20and%20Settings/Adminis nfectious%20Diseases%20General%20Problems.htm (5 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
Granulocytopenia (Neutropenia)
Granulocytopenia is common following hematopoietic cell transplantation ("bone marrow transplantation") and
among patients with solid tumors—as a result of myelosuppressive chemotherapy—and in acute leukemias. The

risk of infection begins to increase when the absolute granulocyte count falls below 1000/mcL, with a
dramatic increase in frequency and severity when the granulocyte count falls below 100/mcL. The infection risk
is also increased when there is a rapid rate of decline of neutrophils and in those with a prolonged period
of neutropenia. The granulocytopenic patient is particularly susceptible to infections with gram-negative
enteric organisms, Pseudomonas, gram-positive cocci (particularly Staphylococcus aureus, S epidermidis,
and viridans streptococci), Candida, Aspergillus, and other fungi that have recently emerged as pathogens such
as Trichosporon, Scedosporium, Fusarium, and Pseudallescheria. The methods used for detection of deficiencies
in the immune system can be found in Allergy & Immunology.
Impaired Cellular Immunity
Patients with cellular immune deficiency encompass a large and heterogeneous group, including patients with
HIV infection (see Infectious Diseases: HIV); patients with lymphoreticular malignancies, such as Hodgkin's
disease; and patients receiving immunosuppressive medications, such as corticosteroids, cyclosporine,
tacrolimus, and other cytotoxic drugs. This latter group—those who are immunosuppressed as a result of
medications—includes patients who have undergone transplantation, many patients receiving therapy for
solid tumors, and patients receiving prolonged high-dose corticosteroid treatment (eg, for asthma, temporal
arteritis, systemic lupus). Patients with cellular immune dysfunction are susceptible to infections by a large number
of organisms, particularly ones that replicate intracellularly. Examples include bacteria, such as Listeria,
Legionella, Salmonella, and Mycobacterium; viruses, such as herpes simplex, varicella, and CMV; fungi, such
as Cryptococcus, Coccidioides, Histoplasma, and Pneumocystis; and protozoa, such as Toxoplasma.
Hematopoietic Cell Transplant Recipients
The length of time it takes for complications to occur in hematopoietic cell transplant recipients can be helpful
in determining the etiologic agent. In the early (preengraftment) posttransplant period (day 1–21), almost
all patients will become severely neutropenic for 7–21 days depending on whether growth factors are used and
the source of stem cells. Patients are at risk for gram-positive (particularly catheter-related) and gram-
negative bacterial infections as well as herpes simplex virus, respiratory syncytial virus, and candidal
infections; mucositis is also a risk factor. In contrast to solid organ transplant recipients, the source of fever
during this period cannot be found in 60–70% of hematopoietic cell transplant patients. Between 3 weeks and
3 months posttransplant, infections with CMV, adenovirus, Aspergillus, and Candida are most common. P
jiroveci pneumonia can also be seen during this period, particularly in patients in whom graft-versus-host
disease (GVHD) has developed and require immunosuppression. Patients continue to be at risk for

infectious complications beyond 3 months following transplantation, particularly those who have received
allogeneic transplantation and those who are taking immunosuppressive therapy for chronic GVHD. Varicella-zoster
is common, and Aspergillus and CMV infections are increasingly seen in this period as well.
Solid Organ Transplant Recipients
The length of time it takes for infection to occur following solid organ transplantation can also be helpful
in determining the infectious origin. Immediate postoperative infections often involve the transplanted
organ. Following lung transplantation, pneumonia and mediastinitis are particularly common; following
liver transplantation, intra-abdominal abscess, cholangitis, and peritonitis may be seen; after renal
transplantation, urinary tract infections, perinephric abscesses, and infected lymphoceles can occur.
file:///C|/Documents%20and%20Settings/Adminis nfectious%20Diseases%20General%20Problems.htm (6 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
Most infections that occur in the first 2–4 weeks posttransplant are related to the operative procedure and
to hospitalization itself (wound infection, intravenous catheter infection, urinary tract infection from a Foley
catheter) or are related to the transplanted organ. Infections that occur between the first and sixth months are
often related to immunosuppression. During this period, reactivation of viruses occurs, and herpes simplex,
varicella-zoster, and CMV infections are quite common. Opportunistic infections with fungi (eg, Candida,
Aspergillus, Cryptococcus, Pneumocystis), Listeria monocytogenes, Nocardia, and Toxoplasma are also
common. After 6 months, if immunosuppression has been reduced to maintenance levels, infections that are found
in any population occur. Patients with poorly functioning allografts who receive long-term
immunosuppression therapy continue to be at risk for opportunistic infections.
Other Immunocompromised States
A large group of patients who are not specifically immunodeficient are at increased risk for infection because
of debilitating injury (eg, burns or severe trauma), invasive procedures (eg, hyperalimentation lines, Foley
catheters, dialysis catheters), central nervous system dysfunction (which predisposes patients to
aspiration pneumonia and decubitus ulcers), obstructing lesions (eg, pneumonia due to an obstructed
bronchus, pyelonephritis due to nephrolithiasis, cholangitis secondary to cholelithiasis), and use of broad-
spectrum antibiotics. Patients with diabetes mellitus have alterations in cellular immunity that make
them disproportionately susceptible to some diseases (eg, mucormycosis, emphysematous pyelonephritis, and
foot infections).
Clinical Findings

Laboratory Findings
Routine evaluation includes complete blood count with differential, chest radiograph, and blood cultures; urine
and sputum cultures should be obtained if indicated clinically or radiographically. Any focal complaints (localized
pain, headache, rash) should prompt imaging and cultures appropriate to the site.
Patients who remain febrile without an obvious source should be evaluated for viral infection (CMV blood cultures
or antigen test), abscesses (which usually occur near previous operative sites), candidiasis involving the liver
or spleen, or aspergillosis. Serologic evaluation may be helpful if toxoplasmosis, aspergillosis (detected
by galactomannan level in serum), or an endemic fungal infection (coccidioidomycosis, histoplasmosis) is a
possible cause.
Special Diagnostic Procedures
Special diagnostic procedures should also be considered. The cause of pulmonary infiltrates can be easily
determined with simple techniques in some situations—eg, induced sputum yields a diagnosis of
Pneumocystis pneumonia in 50–80% of AIDS patients with this infection. In other situations, more
invasive procedures may be required (bronchoalveolar lavage, transbronchial biopsy, or even open lung
biopsy). Other investigations such as skin, liver, or bone marrow biopsy may be helpful in establishing a diagnosis.
Differential Diagnosis
Transplant rejection, organ ischemia and necrosis, thrombophlebitis, and lymphoma
(posttransplant lymphoproliferative disease) may all present as fever and must be considered in the
differential diagnosis.
Prevention
There is great interest in preventing infection with prophylactic antimicrobial regimens but no uniformity of
opinion about optimal drugs or dosage regimens. Hand washing is the simplest and most effective means
of decreasing nosocomial infections in all patients, especially the compromised patient. Invasive devices such
file:///C|/Documents%20and%20Settings/Adminis nfectious%20Diseases%20General%20Problems.htm (7 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
as central and peripheral lines and Foley catheters are a potential source of infection. Some centers use
laminar airflow isolation or high-efficiency particulate air (HEPA) filtering in hematopoietic cell transplant
patients during the neutropenic phase.
Pneumocystis & Herpes Simplex Infections
Trimethoprim-sulfamethoxazole (TMP-SMZ), one double-strength tablet orally three times a week, one

double-strength tablet twice daily on weekends, or one single-strength tablet daily for 3–6 months, is frequently
used to prevent Pneumocystis infections in transplant patients. It may also decrease the incidence of
bacterial pneumonia, urinary tract infections, Nocardia infections, and toxoplasmosis. In patients allergic to TMP-
SMZ, aerosolized pentamidine is used in a dosage of 300 mg once a month, as is dapsone, 50 mg orally daily or
100 mg three times weekly. (Glucose-6-phosphate dehydrogenase (G6PD) levels should be determined
before therapy when the latter is instituted.) Acyclovir prevents herpes simplex infections in bone marrow and
solid organ transplant recipients and is given to seropositive patients who are not receiving acyclovir or ganciclovir
for CMV prophylaxis. The usual dose is 200 mg orally three times daily for 4 weeks (hematopoietic cell transplants)
to 12 weeks (other solid organ transplants).
CMV
Prevention of CMV is more difficult, and no uniformly accepted approach has been adopted. Prevention
strategies often depend on the serologic status of the donor and recipient and the organ transplanted,
which determines the level of immunosuppression after transplant. In solid organ transplants (liver, kidney,
heart, lung), the greatest risk of developing CMV disease is in seronegative patients who receive organs
from seropositive donors. These high-risk patients usually receive ganciclovir, 2.5–5 mg/kg intravenously twice
daily, during hospitalization (usually about 10 days) and then are given oral valganciclovir, 900 mg twice daily,
or oral ganciclovir, 1 g three times daily, for 3 months; of note, oral ganciclovir is not absorbed as well as
oral valganciclovir. Other solid organ transplant recipients (seropositive recipients) are at lower risk for
developing CMV disease and usually receive intravenous ganciclovir while in the hospital followed by either high-
dose oral acyclovir at a dosage of 800 mg four times daily or oral ganciclovir for 3 months. Ganciclovir,
valganciclovir, and acyclovir prevent herpes virus reactivation. Because immunosuppression is increased
during periods of rejection, patients treated for rejection usually receive intravenous ganciclovir during
rejection therapy.
Recipients of hematopoietic cell transplants are more severely immunosuppressed than recipients of solid
organ transplants, are at greater risk for developing serious CMV infection, and thus usually receive more
aggressive prophylaxis. Two approaches have been used: universal prophylaxis or preemptive therapy. In the
former, all high-risk patients (seropositive patients who receive allogeneic transplants) receive 5 mg/kg
of intravenous ganciclovir every 12 hours for a week, followed by oral valganciclovir, 900 mg twice daily, or
oral ganciclovir (which is not absorbed as well as valganciclovir), 1 g three times daily to day 100. This method
is costly and associated with significant toxicity and is therefore being used less frequently. Alternatively, patients

can be monitored without specific therapy and have blood sampled weekly for the presence of CMV. If CMV
is detected by an antigenemia assay, preemptive therapy with ganciclovir is given (5 mg/kg intravenously twice
daily for 7–14 days, followed by oral valganciclovir, 900 mg twice daily for a minimum of 3 weeks or until day
100, whichever is longer). This approach is effective but does miss a small number of patients in whom CMV
disease subsequently develops. Other preventive strategies include use of CMV-negative or leukocyte-depleted
blood products for CMV-seronegative recipients.
Other Organisms
Routine decontamination of the gastrointestinal tract to prevent bacteremia in the neutropenic patient is
file:///C|/Documents%20and%20Settings/Adminis nfectious%20Diseases%20General%20Problems.htm (8 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
not recommended. Prophylactic administration of antibiotics in the afebrile, asymptomatic neutropenic patient
is controversial, although many centers have adopted this strategy. Rates of bacteremia are decreased, but
overall mortality is not affected and emergence of resistant organisms is a common problem. Use of
intravenous immunoglobulin is reserved for the small number of patients with severe
hypogammaglobulinemia following bone marrow transplantation and should not be routinely administered to
all transplant patients.
Prophylaxis with antifungal agents to prevent invasive mold (primarily Aspergillus) and yeast (primarily
Candida) infections is routinely used, but the optimal agent, dose, and duration have not been
standardized. Moderate-dose (0.5 mg/kg/d) and low-dose (0.1–0.25 mg/kg/d) amphotericin B, lipid-
based preparations of amphotericin B, aerosolized amphotericin B, and itraconazole (capsules and solution) have
all been used with varying success in the neutropenic patient. Because voriconazole appears to be more
effective than amphotericin for documented Aspergillus infections, one approach to prophylaxis is to use
oral fluconazole (400 mg/d) for patients at low risk for developing fungal infections (those who receive
autologous bone marrow transplants) and oral voriconazole (200 mg twice daily) for those at high risk
(allogeneic transplants) at least until engraftment (usually 30 days). In solid organ transplant recipients, the risk
of invasive fungal infection varies considerably (1–2% in liver, pancreas, and kidney transplants and 6–8% in
heart and lung transplants). Whether universal prophylaxis or observation with preemptive therapy is the
best approach has not been determined. Although fluconazole is effective in preventing yeast infections,
emergence of resistant strains of Candida krusei, other Candida species, and molds (Fusarium, Aspergillus,
Mucor) has raised concerns about its routine use as a prophylactic agent.

Treatment
General Measures
Because infections in the immunocompromised patient can be rapidly progressive and life-threatening,
diagnostic procedures must be done promptly, and empiric therapy is usually instituted before a specific
pathogenic organism has been isolated.
Reduction or discontinuation of immunosuppressive medication may jeopardize the viability of the
transplanted organ, but in life-threatening infections, it is necessary as an adjunct to effective antimicrobial
therapy. Hematopoietic growth factors (granulocyte and granulocyte-macrophage colony-stimulating
factors) stimulate proliferation of bone marrow stem cells, resulting in an increase in peripheral leukocytes.
These agents shorten the period of neutropenia and have been associated with fewer infections. Use of
growth factors in patients with prolonged neutropenia (> 7 days) is an effective means of
reversing immunosuppression.
Specific Measures
Antimicrobial drug therapy is rationally based on culture results (see Infectious Disease: Antimicrobial
Therapy). Therapy should be specific for isolated pathogens, and bactericidal agents should be used. Combinations
of antimicrobials are often required to provide synergy, to prevent resistance, or to serve as broad-
spectrum coverage of multiple pathogens (since infections in these patients are often polymicrobial).
Empiric therapy is often instituted at the earliest sign of infection in the immunosuppressed patient because
prompt therapy favorably affects outcome. The antibiotic or combination of antibiotics used depends on the type
of immunocompromise and the site of infection. For example, in the febrile neutropenic patient, the primary
concern is bacterial and fungal infections. In this patient population, an algorithmic approach to therapy is often
used, with initial treatment directed at gram-positive and gram-negative organisms. If the patient does not
file:///C|/Documents%20and%20Settings/Adminis nfectious%20Diseases%20General%20Problems.htm (9 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
respond, broader-spectrum antibiotics and antifungal drugs are added. Although a number of different agents can
be used, choices should be based on local microbiologic trends. One example would be to initiate therapy with
a fluoroquinolone active against gram-positive organisms (such as levofloxacin, gatifloxacin, or moxifloxacin)
when the absolute neutrophil count falls below 500/mcL. If fever develops, cultures are obtained, and
vancomycin, 10–15 mg/kg intravenously every 12 hours, is given to cover methicillin-resistant S aureus,
S epidermidis, and enterococcus. If fever continues after 48–72 hours, antifungal coverage can be increased

by changing to either caspofungin, 50 mg daily intravenously, or voriconazole, 200 mg intravenously or orally
twice daily (if the patient was receiving fluconazole prophylaxis); broader-spectrum antibiotics can be
added sequentially. For example, to better cover Acinetobacter, Citrobacter, and Pseudomonas, the
fluoroquinolone may be switched to cefepime, 2 g every 8 hours intravenously; with continued fever, imipenem,
500 mg intravenously every 6 hours (or meropenem, 1 g intravenously every 8 hours), with or without
tobramycin, 1.8 mg/kg intravenously every 8 hours, may be used in place of cefepime. If fevers persist, TMP-SMZ
at 10 mg/kg/d (of trimethoprim) intravenously in three divided doses can be added to cover
Stenotrophomonas. Regardless of whether the patient becomes afebrile, therapy is continued until resolution
of neutropenia. Failure to continue antibiotics through the period of neutropenia is associated with a high incidence
of relapse that can be associated with septic shock.
Patients with fever and neutropenia who are at low risk for developing complications (neutropenia expected to
persist for less than 10 days, no comorbid complications requiring hospitalization, and cancer adequately treated)
can be treated with oral antibiotic regimens, such as ciprofloxacin, 750 mg every 12 hours, plus amoxicillin-
clavulanic acid, 500 mg every 8 hours. In the organ transplant patient with interstitial infiltrates, the main concern
is infection with Pneumocystis or Legionella species, so that empiric treatment with a macrolide and TMP-SMZ
would be reasonable. If the patient does not respond to empiric treatment, a decision must be made to add
more antimicrobial agents or perform invasive procedures (see above) to make a specific diagnosis. By making
a specific diagnosis, therapy can be specific and polypharmacy with multiple potentially toxic agents can be avoided.
Bucaneve G et al: Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Engl J
Med 2005;353:977. [PMID: 16148283]

Kalil AC et al: Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid
organ transplant recipients. Ann Intern Med 2005;143:870. [PMID: 16365468]

Rubin RH: The direct and indirect effects of infection in liver transplantation: pathogenesis, impact, and
clinical management. Curr Clin Top Infect Dis 2002;22:125. [PMID: 12520651]

Viscoli C et al: Treatment of febrile neutropenia: what is new? Curr Opin Infect Dis 2002;15:377. [PMID: 12130933]

Walsh TJ et al: Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients

with persistent fever and neutropenia. N Engl J Med 2004;351:1391. [PMID: 15459300]

file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (10 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
Nosocomial Infections
Essentials of Diagnosis
● Nosocomial infections are defined as those not present or incubating at the time of hospital admission and
developing 48–72 hours after admission.
● Hand washing is the easiest and most effective means of preventing nosocomial infections and should be
done routinely even when gloves are worn.
General Considerations
In the United States, approximately 5% of patients who enter the hospital free of infection acquire a nosocomial
infection, resulting in prolongation of the hospital stay, increase in cost of care, significant morbidity, and a 5%
mortality rate. The most common infections are urinary tract infections, usually associated with Foley catheters or
urologic procedures; bloodstream infections, most commonly from indwelling catheters but also from secondary
sites, such as surgical wounds, abscesses, pneumonia, the genitourinary tract, and the gastrointestinal tract;
pneumonia in intubated patients or those with altered levels of consciousness; surgical wound infections; and
Clostridium difficile colitis.
Some general principles are helpful in preventing, diagnosing, and treating nosocomial infections:
1. Many infections are a direct result of the use of invasive devices for monitoring or therapy such as intravenous
catheters, Foley catheters, shunts, surgical drains, catheters placed by interventional radiology for drainage,
nasogastric tubes and orotracheal or nasotracheal tubes for ventilatory support. Early removal of such devices
reduces the possibility of infection.
2. Patients in whom nosocomial infections develop are often critically ill, have been hospitalized for extended periods,
and have received several courses of broad-spectrum antibiotic therapy. As a result, nosocomial infections are often
caused by organisms that are multidrug resistant and are different from those encountered in community-acquired
infections. Examples are S aureus and S epidermidis (a frequent cause of prosthetic device infection) that may be
resistant to nafcillin and cephalosporins and require vancomycin for therapy; Enterococcus faecium resistant to
ampicillin and vancomycin; gram-negative infections caused by Pseudomonas, Citrobacter, Enterobacter,
Acinetobacter, and Stenotrophomonas, which may be sensitive only to fluoroquinolones, carbapenems,

aminoglycosides, or TMP-SMZ. When choosing antibiotics to treat the seriously ill patient with a nosocomial infection,
the previous antimicrobial the patient has received as well as the "local ecology" must be considered. It is often
necessary to institute therapy with vancomycin and a carbapenem or aminoglycoside until a specific agent is isolated
and sensitivities are known, at which time the least toxic and most cost-effective drug can be used.
One promising approach to preventing the development of multidrug-resistant organisms is antibiotic cycling. By
changing the class of antibiotic primarily used every 6–12 months (eg, a cephalosporin, then fluoroquinolones, then
carbapenems), selection pressure is decreased and less resistance emerges.
Because widespread use of antimicrobial drugs contributes to the selection of drug-resistant organisms that cause
nosocomial infections, every effort should be made to limit the use of antibiotics to treat documented infections. All
too often, unreliable or uninterpretable specimens are obtained for culture that result in unnecessary use of
antibiotics. The best example of this principle is the diagnosis of line-related or bloodstream infection in the febrile
patient (see below). To avoid unnecessary use of antibiotics, thoughtful consideration of culture results is mandatory.
A positive wound culture without signs of inflammation or infection, a positive sputum culture without pulmonary
infiltrates on chest x-ray, or a positive urine culture in a catheterized patient without symptoms or signs of
pyelonephritis are all likely to represent colonization, not infection.
file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (11 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
Clinical Findings
Symptoms and Signs
Catheter-associated infections have a variable presentation, depending on the type of catheter used (peripheral or
central venous catheters, nontunneled or tunneled). Local signs of infection may be present at the insertion site, with
pain, erythema, and purulence. Fever is often absent in uncomplicated infections and if present, may indicate more
disseminated disease such as bacteremia, cellulitis and septic thrombophlebitis. Often signs of infection at the
insertion site are absent.
Fever in an intensive care unit patient
Fever complicates up to 70% of patients in intensive care units, and the etiology of the fever may be infectious or
noninfectious. Common infectious causes include catheter-associated infections, hospital-acquired and ventilator-
associated pneumonia (see Pulmonology), surgical site infections, urinary tract infections, and sepsis. Clinically
relevant sinusitis is relatively uncommon in the patient in the intensive care unit.
An important noninfectious cause is thromboembolic disease. Fever in conjunction with refractory hypotension and

shock may suggest sepsis; however, adrenal insufficiency, thyroid storm, and transfusion reaction may have a
similar clinical presentation. Drug fever is difficult to diagnose and is usually a diagnosis of exclusion unless there are
other signs of hypersensitivity, such as a typical maculopapular rash.
Fever in the postoperative patient
Postoperative fever is very common and in many cases resolves spontaneously. Etiologies are both infectious and
noninfectious. Timing of the fever in relation to the surgery and the nature of the surgical procedure may help
diagnostically.
Immediate fever (in the first few hours after surgery)
Immediate fever can be due to medications that were given perioperatively, to the trauma of surgery itself, or to
infections that were present before surgery. Necrotizing fasciitis due to group A streptococci or mixed organisms may
present in this period. Malignant hyperthermia is rare and presents 30 minutes to several hours following inhalational
anesthesia (succinylcholine or halothane commonly) and is characterized by extreme hyperthermia, muscle rigidity,
rhabdomyolysis, electrolyte abnormalities, and hypotension. Aggressive cooling and dantrolene are the mainstays of
therapy. Fever due to the trauma of surgery itself usually resolves in 2–3 days, longer in more complicated operative
cases and in patients with head trauma.
Acute fever (within 1 week of surgery)
Acute fever is usually due to common causes of nosocomial infections, such as ventilator-associated pneumonia
(including aspiration pneumonia in patients with decreased gag reflex) and line infections. Noninfectious causes
include alcohol withdrawal, gout, pulmonary embolism, and pancreatitis.
Subacute fever (at least 1 week after surgery)
Surgical site infections commonly present at least 1 week after surgery. The type of surgery that was performed may
be related to specific infectious etiologies. Patients undergoing cardiothoracic surgery may be at higher risk for
pneumonia and deep and superficial sternal wound infections. Meningitis without typical signs of meningismus may
complicate neurosurgical procedures. Abdominal surgery may result in deep abdominal abscesses that require
drainage.
Laboratory Findings
Blood cultures are universally recommended, and chest radiographs are frequently obtained. Sputum Gram stain and
semi-quantitative sputum cultures are useful in selected patients where there is a high pretest probability of
pneumonia. Other diagnostic strategies will be dictated by the clinical context (eg, transesophageal echocardiogram
file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (12 of 54) [14/12/2006 8:12:28 μμ]

AccessMedicine - Print
in a patient with S aureus bacteremia).
Any fever in a patient with a central venous catheter should prompt the collection of blood. The best method to
evaluate bacteremia is to gather at least two peripherally obtained blood cultures. Blood cultures from unidentified
sites, a single blood culture from any site, or a blood culture through an existing line will often be positive for S
epidermidis and may lead to therapy with vancomycin. Yet, the likelihood that such a culture represents a true
bacteremia is 10–20%. Unless two separate venipuncture cultures are obtained—not through catheters—
interpretation of results is impossible and unnecessary therapy is given. Every such "pseudobacteremia" increases
laboratory costs, antibiotic use, and length of stay, increasing costs of hospitalization by about $4500. Microbiologic
evaluation of the removed catheter can sometimes be helpful, but only in addition to (not instead of) blood cultures
drawn from peripheral sites. Semiquantitative cultures of the catheter is performed by rolling the distal 2 cm tip of
the catheter on an agar plate. The presence of > 15 colony-forming units (CFU) of organisms on the catheter tip
together with identical organisms on peripherally drawn blood cultures establishes the diagnosis of a catheter-
associated bloodstream infection. Other methods may permit catheters to remain in place while infection is being
ruled out. The differential time to positivity measures the difference in time that cultures simultaneously drawn
through a catheter and a peripheral site become positive. A positive test (about 120 minutes difference in time)
supports a catheter-related bloodstream infection, and a negative test may permit catheters to be retained.
Complications
Patients who have persistent bacteremia and continue to be febrile despite removal of the infected catheter may
have complications such as septic thrombophlebitis, endocarditis, or metastatic foci of infection (particularly with S
aureus). Additional studies such as venous Doppler studies, transesophageal echocardiogram, and chest radiographs
may be indicated. Duration of therapy is longer, usually 4–6 weeks. In the case of septic thrombophlebitis,
anticoagulation with heparin is also recommended if there are no contraindications.
Differential Diagnosis
Although most fevers are due to infections, about 25% of patients will have fever of noninfectious origin. These
include drug fever, nonspecific postoperative fevers (atelectasis, tissue damage or necrosis), hematoma,
pancreatitis, pulmonary embolism, myocardial infarction, and ischemic bowel disease.
Prevention
Prevention is of paramount importance in controlling nosocomial infections. The concept of universal precautions
emphasizes that all patients are treated as though they have a potential blood-borne transmissible disease, and thus

all body secretions are handled with care to prevent spread of disease. Almost all hospitals have implemented body
substance isolation, which requires use of gloves whenever a health care worker anticipates contact with blood or
other body secretions. By wearing gloves, health care workers prevent contamination of their hands with infected
secretions and subsequent spread of infection to other patients by direct contact. Even though gloves are worn,
health care workers should routinely wash their hands, since it is the easiest and most effective means of preventing
nosocomial infections. Application of a rapid drying, alcohol-based antiseptic is easy to do, takes less time than
traditional hand washing with soap and water, is more effective at reducing hand colonization, promotes compliance
with hand decontamination, and is rapidly becoming the method of choice for hand disinfection.
Peripheral intravenous lines should be replaced every 3 days, and arterial lines should be replaced every 4 days.
Lines in the central venous circulation (including those placed peripherally) can be left in place indefinitely and are
changed or removed when they are clinically suspected of being infected, when they are nonfunctional, or when they
are no longer needed. Silver alloy–impregnated Foley catheters reduce the incidence of catheter-associated
file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (13 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
bacteriuria, and antibiotic-impregnated (minocycline plus rifampin or chlorhexidine plus silver sulfadiazine) venous
catheters reduce line infections and bacteremia. Whether the increased cost of these devices justifies their routine
use should be determined by individual institutions based on local infection rates. Selective decontamination of the
digestive tract with nonabsorbable antibiotics to prevent nosocomial pneumonia is widely used in Europe, but the
therapeutic efficacy of this expensive intervention is controversial.
Attentive nursing care (positioning to prevent decubitus ulcers, wound care, elevating the head during tube feedings
to prevent aspiration) is critical in preventing nosocomial infections. In addition, monitoring of high-risk areas by
hospital epidemiologists detects increases in infection rates early and is a key factor in prevention of these types of
infections.
Several highly effective vaccines have been approved by the US Food and Drug Administration (FDA) that add to the
armamentarium for preventing certain nosocomial infections. Hepatitis A, hepatitis B, and the varicella vaccine
should be considered in the appropriate setting. (See section below on Immunization Against Infectious Diseases.)
Treatment
Fever in an Intensive Care Unit patient
Unless the patient has a central neurologic injury with elevated intracranial pressure or has a temperature > 41 °C,
there is less physiologic need to maintain euthermia. Empiric broad-spectrum antibiotics (as noted above) are

recommended for neutropenic and other immunocompromised patients and in patients who are clinically unstable.
Catheter-Associated Infections
Factors that inform treatment decisions include the type of catheter that is affected, the type of organism, the
availability of alternate catheter access sites, the need for ongoing intravascular access, and the extent of disease
involved.
In general, catheters should be removed if there is purulence at the exit site; if the organism is S aureus, gram-
negative rods, or Candida species; if there is persistent bacteremia (> 48 hours while receiving antibiotics); or if
complications, such as septic thrombophlebitis, endocarditis, or other metastatic disease exist. Central venous
catheters may be exchanged over a guidewire and the tip sent for semiquantitative cultures if a catheter infection is
suspected, provided there is no erythema or purulence at the exit site and the patient does not appear to be septic.
If the catheter tip cultures return with > 15 CFU, replacement of the catheter at a new site is recommended. Given
that coagulase-negative staphylococci are the most common organisms isolated and most are resistant to nafcillin,
empiric therapy with vancomycin, 15 mg/kg IV twice daily, should be given to patients in whom a bloodstream
infection is suspected and who have normal renal function. Empiric gram-negative coverage may be considered in
patients who are immunocompromised or who are critically ill.
Antibiotic treatment duration depends on the organism identified and the extent of disease. For uncomplicated
bacteremia, 5–7 days of therapy is usually sufficient for coagulase-negative staphylococci, even if the original
catheter is retained. Fourteen days of therapy is generally recommended for uncomplicated bacteremia caused by
gram-negative rods, Candida species, and S aureus.
Kollef MH: Prevention of hospital-associated pneumonia and ventilator-associated pneumonia. Crit Care Med
2004;32:1396. [PMID: 15187525]

Lorente C et al: Prevention of infection in the intensive care unit: current advances and opportunities for the future.
Curr Opin Crit Care 2002;8:461. [PMID: 12357116]

file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (14 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
Raad I et al: Differential time to positivity: a useful method for diagnosing catheter-related bloodstream infections.
Ann Intern Med 2004;140:18. [PMID: 14706968]

Vermeulen H et al: Diagnostic accuracy of routine postoperative body temperature measurements. Clin Infect Dis
2005;40:1404. [PMID: 15844061]

Vincent JL: Nosocomial infections in adult intensive-care units. Lancet 2003;361:2068. [PMID: 12814731]

Infections of the Central Nervous System
Essentials of Diagnosis
● Central nervous system infection is a medical emergency.
● Symptoms and signs common to all types of central nervous system infection include headache, fever, sensorial
disturbances, neck and back stiffness, positive Kernig and Brudzinski signs, and cerebrospinal fluid abnormalities.
General Considerations
Infections of the central nervous system can be caused by almost any infectious agent, including
bacteria, mycobacteria, fungi, spirochetes, protozoa, helminths, and viruses. The classic triad of fever, stiff neck
and altered mental status has a low sensitivity (44%) for bacterial meningitis. However, nearly all patients
with bacterial meningitis have at least two of the following symptoms—fever, headache, stiff neck, or altered
mental status.
Etiologic Classification
Central nervous system infections can be divided into several categories that usually can be readily
distinguished from each other by cerebrospinal fluid examination as the first step toward etiologic diagnosis
(Table 30–1 and Figure: illustration).
Table 30–1. Typical cerebrospinal fluid findings in various central nervous
system diseases.

Diagnosis Cells/mcL Glucose
(mg/dL)
Protein (mg/
dL)
Opening
Pressure
Normal 0–5 lymphocytes

45–85
1


15–45 70–180 mm H
2
O

Purulent meningitis (bacterial)
2

community-acquired

200–20,000
polymorphonuclear neutrophils
Low (< 45) High (> 50) Markedly elevated
Granulomatous meningitis
(mycobacterial, fungal)
3


100–1000, mostly
lymphocytes
3


Low (< 45) High (> 50) Moderately
elevated
Spirochetal meningitis 100–1000, mostly
lymphocytes

3


Normal Moderately high
(> 50)
Normal to slightly
elevated
Aseptic meningitis, viral or
meningoencephalitis
4


25–2000, mostly
lymphocytes
3


Normal or low High (> 50) Slightly elevated
"Neighborhood reaction"
5


Variably increased Normal Normal or high Variable
file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (15 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print

1
Cerebrospinal fluid glucose must be considered in relation to blood glucose level. Normally, cerebrospinal
fluid glucose is 20–30 mg/dL lower than blood glucose, or 50–70% of the normal value of blood glucose.
2

Organisms in smear or culture of cerebrospinal fluid; counterimmunoelectrophoresis or latex agglutination may
be diagnostic.
3
Polymorphonuclear neutrophils may predominate early.
4
Viral isolation from cerebrospinal fluid early; antibody titer rise in paired specimens of serum; polymerase
chain reaction for herpesvirus.
5
May occur in mastoiditis, brain abscess, epidural abscess, sinusitis, septic thrombus, brain tumor. Cerebrospinal
fluid culture results usually negative.
Collection of cerebrospinal fluid. (Reproduced, with permission, from Chesnutt MS et al: Office & Bedside
Procedures. Originally published by Appleton & Lange. Copyright © 1992 by The McGraw-Hill Companies, Inc.)
Purulent Meningitis
Patients with bacterial meningitis usually seek medical attention within hours or 1–2 days after onset of
symptoms. The organisms responsible depend primarily on the age of the patient as summarized in Table 30–2.
The diagnosis is usually based on the Gram-stained smear (positive in 60–90%) or culture (positive in over 90%).
Table 30–2. Initial antimicrobial therapy for purulent meningitis of unknown cause.

Population Common Microorganisms Standard Therapy
18–50 years Streptococcus pneumoniae,
Neisseria meningitidis
Vancomycin
1
plus cefotaxime or ceftriaxone
2


Over 50 years S pneumoniae, N meningitidis,
Listeria monocytogenes, gram-
negative bacilli

Vancomycin
1
plus ampicillin,
3
plus cefotaxime or ceftriaxone
2


Impaired cellular
immunity
L monocytogenes, gram-negative
bacilli, S pneumoniae
Vancomycin
1
plus ampicillin
3
plus ceftazidime
4


file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (16 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
Postsurgical or
posttraumatic
Staphylococcus aureus, S
pneumoniae, gram-negative bacilli
Vancomycin
1
plus ceftazidime
4

1
The dose of vancomycin is 10–15 mg/kg IV every 6 hours.
2
The usual dose of cefotaxime is 2 g IV every 6 hours and that of ceftriaxone is 2 g IV every 12 hours. If
the organism is sensitive to penicillin, 3–4 million units IV every 4 hours is given.
3
The dose of ampicillin is usually 2 g IV every 4 hours.
4
Ceftazidime is given in a dose of 50–100 mg/kg IV every 8 hours up to 2 g every 8 hours.
Chronic Meningitis
The presentation of chronic meningitis is less acute than purulent meningitis. Patients with chronic meningitis
usually have a history of symptoms lasting weeks to months. The most common pathogens are
Mycobacterium tuberculosis, atypical mycobacteria, fungi (Cryptococcus, Coccidioides, Histoplasma), and
spirochetes (Treponema pallidum and Borrelia burgdorferi, the cause of Lyme disease). The diagnosis is made
by culture or in some cases by serologic tests (cryptococcosis, coccidioidomycosis, syphilis, Lyme disease).
Aseptic Meningitis
Aseptic meningitis—a much more benign and self-limited syndrome than purulent meningitis—is caused principally
by viruses, especially mumps virus and the enterovirus group (including coxsackieviruses and
echoviruses). Infectious mononucleosis may be accompanied by aseptic meningitis. Leptospiral infection is
also usually placed in the aseptic group because of the lymphocytic cellular response and its relatively benign
course. This type of meningitis also occurs during secondary syphilis and disseminated Lyme disease.
Encephalitis
Encephalitis (due to herpesviruses, arboviruses, rabies virus, flaviviruses [West Nile encephalitis,
Japanese encephalitis], and many others) produces disturbances of the sensorium, seizures, and many
other manifestations. Patients are more ill than those with aseptic meningitis. Cerebrospinal fluid may be
entirely normal or may show some lymphocytes and in some instances (eg, herpes simplex) red cells as well.
Partially Treated Bacterial Meningitis

Previous effective antibiotic therapy given for 12–24 hours will decrease the rate of positive Gram stain results
by 20% and culture by 30–40% but will have little effect on cell count, protein, or glucose. Occasionally,
previous antibiotic therapy will change a predominantly polymorphonuclear response to a lymphocytic
pleocytosis, and some of the cerebrospinal fluid findings may be similar to those seen in aseptic meningitis.
Neighborhood Reaction
As noted in Table 30–1, this term denotes a purulent infectious process in close proximity to the central
nervous system that spills some of the products of the inflammatory process—white blood cells or protein—into
the cerebrospinal fluid. Such an infection might be a brain abscess, osteomyelitis of the vertebrae, epidural
abscess, subdural empyema, or bacterial sinusitis or mastoiditis.
Noninfectious Meningeal Irritation
Carcinomatous meningitis, sarcoidosis, systemic lupus erythematosus, chemical meningitis, and certain drugs
—nonsteroidal anti-inflammatory drugs, muromonab-CD3 (OKT3), TMP-SMZ, and others—can also
produce symptoms and signs of meningeal irritation with associated cerebrospinal fluid pleocytosis, increased
protein, and low or normal glucose. Meningismus with normal cerebrospinal fluid findings occurs in the presence
of other infections such as pneumonia and shigellosis.
Brain Abscess
file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (17 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
Brain abscess presents as a space-occupying lesion; symptoms may include vomiting, fever, change of mental
status, or focal neurologic manifestations. When brain abscess is suspected, a CT scan should be performed.
If positive, lumbar puncture should not be performed since results rarely provide clinically useful information
and herniation can occur. The bacteriology of brain abscess is usually polymicrobial and includes S aureus,
gram-negative bacilli, streptococci, and anaerobes (including anaerobic streptococci and Prevotella species).
Amebic Meningoencephalitis
These infections are caused by free-living amebas and present as two distinct syndromes. The diagnosis is
confirmed by culture (Acanthamoeba spp. and Balamuthia mandrillaris) or identification of the organism in a
wet mount of cerebrospinal fluid (Naegleria fowleri) or on biopsy specimens. No effective therapy is available.
Primary amebic meningoencephalitis is caused by N fowleri and is an acute fulminant disease, usually seen in
children and young adults with recent fresh water exposure, and is characterized by signs of meningeal irritation
that rapidly progresses to encephalitis and death. Rare cures have been reported with intravenous

and intraventricular administration of amphotericin B.
Granulomatous amebic encephalitis is caused by Acanthamoeba species. It is an indolent disease, frequently seen
in immunocompromised patients and associated with cutaneous lesions. Central nervous system disease
is characterized by headache, nausea, vomiting, cranial neuropathies, seizures, and hemiparesis. Infections
with Balamuthia are similar to Acanthamoeba in that the course is subacute to chronic, but unlike
Acanthamoeba both immunocompromised and immunocompetent persons can be affected.
Clinical Findings
Laboratory Tests
Evaluation of a patient with suspected meningitis includes a history, physical examination, blood count, blood
culture, lumbar puncture followed by careful study and culture of the cerebrospinal fluid, and a chest film. The
fluid must be examined for cell count, glucose, and protein, and a smear stained for bacteria (and acid-
fast organisms when appropriate) and cultured for pyogenic organisms and for mycobacteria and fungi
when indicated. Latex agglutination tests can detect antigens of encapsulated organisms (S pneumoniae,
H influenzae, N meningitidis, and Cryptococcus neoformans) but are rarely used except for detection of
Cryptococcus or in partially treated patients. Polymerase chain reaction (PCR) testing of cerebrospinal fluid has
been used to detect bacteria (S pneumoniae, H influenzae, N meningitidis, M tuberculosis, B burgdorferi,
and Tropheryma whippelii) and viruses (herpes simplex, varicella-zoster, CMV, Epstein-Barr virus, and
enteroviruses) in patients with meningitis. The greatest experience is with PCR for herpes simplex and
varicella-zoster, and the tests are very sensitive (> 95%) and specific. Tests to detect the other organisms may
not be any more sensitive than culture, but the real value is the rapidity with which results are available, ie,
hours compared with days or weeks. At present, with the exception of PCR for herpes simplex, these tests
are performed only in reference laboratories. Although it is difficult to prove with existing clinical data that
early antibiotic therapy improves outcome in bacterial meningitis, prompt therapy is still recommended.
Lumbar Puncture and Imaging
Since performing a lumbar puncture in the presence of a space-occupying lesion (brain abscess, subdural
hematoma, subdural empyema, necrotic temporal lobe from herpes encephalitis) may result in brainstem
herniation, a CT scan is performed prior to lumbar puncture if a space-occupying lesion is suspected on the basis
of papilledema, seizures, or focal neurologic findings. Other indications for CT scan are an
immunocompromised patient or moderate to severely impaired level of consciousness. If delays are encountered
in obtaining a CT scan and bacterial meningitis is suspected, blood cultures should be drawn and antibiotics

file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (18 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
and corticosteroids administered even before cerebrospinal fluid is obtained for culture to avoid delay in
treatment (Table 30–2). Antibiotics given within 4 hours before obtaining cerebrospinal fluid probably do not
affect culture results.
Treatment
Increased intracranial pressure due to brain edema often requires therapeutic attention. Hyperventilation,
mannitol (25–50 g as a bolus intravenous infusion), and even drainage of cerebrospinal fluid by repeated
lumbar punctures or by placement of ventricular catheters have been used to control cerebral edema and
increased intracranial pressure. Dexamethasone (4 mg intravenously every 4–6 hours) may also decrease
cerebral edema. In purulent meningitis, the identity of the causative microorganism may remain unknown or
doubtful for a few days and initial antibiotic treatment as set forth in Table 30–2 should be directed against
the microorganisms most common for each age group.
The duration of therapy for bacterial meningitis varies depending on the etiologic agent: H influenzae, 7 days;
N meningitidis, 3–7 days; S pneumoniae, 10–14 days; L monocytogenes, 14–21 days; and gram-negative bacilli,
21 days.
Dexamethasone therapy is recommended for adults with pneumococcal meningitis. Ten milligrams of
dexamethasone administered intravenously 15–20 minutes before or simultaneously with the first dose of
antibiotics and continued every 6 hours for 4 days decreases morbidity and mortality. The number of patients
with meningitis due to N meningitidis and other bacterial pathogens studied does not support similar
conclusions. However, because adverse effects of dexamethasone for short periods are few and because
potential benefits are great, many clinicians would advocate dexamethasone even if N meningitidis is the
causative agent.
Therapy of brain abscess consists of drainage (excision or aspiration) in addition to 3–4 weeks of systemic
antibiotics directed against organisms isolated. A regimen often used includes metronidazole, 500 mg
intravenously or orally every 8 hours, plus ceftizoxime, 2 g intravenously every 8 hours, or ceftriaxone, 2 g every
12 hours. In cases where abscesses are less than 2 cm in size, where there are multiple abscesses that cannot
be drained, or if an abscess is located in an area where significant neurologic sequelae would result from
drainage, antibiotics for 6–8 weeks without drainage can be used.
Therapy of other types of meningitis is discussed elsewhere in this book (fungal meningitis, Infectious

Diseases: Mycotic; syphilis and Lyme borreliosis, Infectious Diseases: Bacterial & Chlamydial; tuberculous
meningitis, Infectious Diseases: Sprirochetal; herpes encephalitis, Infectious Diseases: Viral & Rickettsial).
Bernardini GL: Diagnosis and management of brain abscess and subdural empyema. Curr Neurol Neurosci
Rep 2004;4:448. [PMID: 15509445]

De Gans J et al: Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002;347:1549. [PMID: 11144034]

Sinner SW et al: Antimicrobial agents in the treatment of bacterial meningitis. Infect Dis Clin North Am
2004;18:581. [PMID: 15308277]

van de Beek D et al: Community-acquired bacterial meningitis in adults. N Engl J Med 2006;354:44.
[PMID: 16394301]

file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (19 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
Animal & Human Bite Wounds
Essentials of Diagnosis
● Cat and human bites are more likely to become infected than dog bites.
● Bites to the hand are of special concern because of the possibility of closed-space infection.
● Antibiotic prophylaxis indicated for noninfected bites of the hand and hospitalization required for infected hand bites.
● All infected wounds need to be cultured to direct therapy.
General Considerations
About 1000 dog bite injuries require emergency department attention each day, most often in urban areas. Dog
bites occur most commonly in the summer months. Biting animals are usually known by their victims, and
most biting incidents are provoked (ie, bites occur while playing with the animal or after surprising the animal
or waking it abruptly from sleep). Failure to elicit a history of provocation is important, because an unprovoked
attack raises the possibility of rabies. Human bites are usually inflicted by children while playing or fighting; in
adults, bites are associated with alcohol use and closed-fist injuries that occur during fights.
The animal inflicting the bite, the location of the bite, and the type of injury inflicted are all important determinants
of whether they become infected. Cat bites are more likely to become infected than human bites—between 30%

and 50% of all cat bites become infected. Infections following human bites are variable: Those inflicted by
children rarely become infected because they are superficial, and bites by adults become infected in 15–30%
of cases, with a particularly high rate of infection in closed-fist injuries. "Through and through" bites (eg involving
the mucosa and the skin) have an infection rate similar to closed-fist injuries. Dog bites, for unclear reasons,
become infected only 5% of the time. Bites of the head, face, and neck are less likely to become infected than
bites on the extremities. Puncture wounds become infected more frequently than lacerations, probably because
the latter are easier to irrigate and debride.
The bacteriology of bite infections is polymicrobial. Following dog and cat bites, over 50% of infections are caused
by aerobes and anaerobes and 36% are due to aerobes alone. Pure anaerobic infections are rare. Pasteurella
species are the single most common isolate (75% of cat bites and 50% of dog bites). Other common aerobic
isolates include streptococci, staphylococci, Moraxella, and Neisseria; the most common anaerobes
are Fusobacterium, Bacteroides, Porphyromonas, and Prevotella. The median number of isolates following
human bites is four (three aerobes and one anaerobe). Like dog and cat bites, most human bites are a mixture
of aerobes and anaerobes (54%) or are due to aerobes alone (44%). Streptococcus, Staphylococcus, and
Eikenella corrodens (found in 30% of patients) are the most common aerobes. Prevotella and Fusobacterium are
the most common anaerobes. Although the organisms noted are the most common, innumerable others have
been isolated—including Capnocytophagia (dog and cats), Pseudomonas, and Haemophilus—emphasizing the
point that all infected bites should be cultured to define the microbiology.
HIV can be transmitted from bites (either from biting or receiving a bite from an HIV-infected patient) but has
rarely been reported.
Treatment
Local Care
Vigorous cleansing and irrigation of the wound as well as debridement of necrotic material are the most
important factors in decreasing the incidence of infections. Radiographs should be obtained to look for fractures
and the presence of foreign bodies. Careful examination to assess the extent of the injury (tendon laceration,
joint space penetration) is critical to appropriate care.
file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (20 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
Suturing
If wounds require closure for cosmetic or mechanical reasons, suturing can be done. However, one should

never suture an infected wound, and wounds of the hand should generally not be sutured since a closed-
space infection of the hand can result in loss of function.
Prophylactic Antibiotics
Prophylaxis is indicated in high-risk bites, eg, cat bites in any location (dicloxacillin, 0.5 g orally four times a day
for 3–5 days) and hand bites by any animal or by humans (penicillin V, 0.5 g orally four times a day for 3–5
days). Although dicloxacillin and penicillin have been specifically studied, there is concern about their use because
of their narrow spectrum of activity. Based on the microbiology of bite wounds, other agents less adequately
studied but that have broader spectrums of activity may be better as prophylactic agents. Examples
include cefuroxime, amoxicillin-clavulanic acid and, in the penicillin-allergic patient, clindamycin plus
a fluoroquinolone. Immunocompromised patients and especially individuals without functional spleens are at risk
for developing overwhelming bacteremia (primarily with Capnocytophagia spp.) and sepsis following animal bites
and should also receive prophylaxis, even for low-risk bites.
Because the risk of HIV transmission is so low following a bite, routine postexposure prophylaxis is
not recommended. Each case should be evaluated individually and consideration for prophylaxis should be given
to those who present within 72 hours of the incident, the source is known to be HIV infected, and the exposure
is high risk.
Antibiotics
For wounds that are infected, antibiotics are clearly indicated. How they are given (orally or intravenously) and
the need for hospitalization are individualized clinical decisions. In general, Pasteurella multocida is best treated
with penicillin or a tetracycline. Other active agents include second- and third-generation
cephalosporins, fluoroquinolones, or azithromycin and clarithromycin. Response to therapy is slow, and
therapy should be continued for at least 2–3 weeks. Human bites frequently require intravenous therapy with a
-lactam plus a -lactamase inhibitor combination (Unasyn, Timentin, Zosyn), a second-generation
cephalosporin with anaerobic activity (cefoxitin, cefotetan, cefmetazole) or, in the penicillin-allergic
patient, clindamycin plus a fluoroquinolone. Because the bacteriology of these infections is so variable,
infected woulds should always be cultured.
Tetanus and Rabies
All patients must be evaluated for the need for tetanus (see Infectious Diseases: Bacterial & Chlamydial) and
rabies (see Infectious Diseases: Viral & Rickettsial) prophylaxis.
Brook I: Microbiology and management of human and animal bite wound infections. Prim Care 2003;30:25.

[PMID: 12825249]

Talan DA et al: Clinical presentation and bacteriologic analysis of infected human bites in patients presenting
to emergency departments. Clin Infect Dis 2003;37:1481. [PMID: 14614671]

Taplitz RA: Managing bite wounds. Currently recommended antibiotics for treatment and prophylaxis. Postgrad
Med 2004;116:49. [PMID: 15323154]

file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (21 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
Sexually Transmitted Diseases
Some infectious diseases are transmitted most commonly—or most efficiently—by sexual contact. Most of the
infectious agents that cause sexually transmitted diseases are fairly easily inactivated when exposed to a harsh
environment. They are thus particularly suited to transmission by contact with mucous membranes. They may be
bacteria, spirochetes, chlamydiae, viruses, or protozoa. In most infections caused by these agents, early lesions
occur on genitalia or other sexually exposed mucous membranes; however, wide dissemination may occur, and
involvement of nongenital tissues and organs may mimic many noninfectious disorders. All sexually transmitted
diseases have subclinical or latent phases that play an important role in long-term persistence of the infection or in
its transmission from infected (but largely asymptomatic) persons to other contacts. Laboratory examinations are
of particular importance in the diagnosis of such asymptomatic patients. Simultaneous infection by several
different agents is common, and any person with a sexually transmitted disease should be tested for syphilis; a
repeat study should be done in 3 months if negative, since seroconversion is delayed after primary infection.
For each patient, there are one or more sexual contacts who require diagnosis and treatment. Prompt treatment of
contacts by giving antibiotics to the index case to distribute all sexual contacts is an important strategy for
preventing further transmission. The most common sexually transmitted diseases are gonorrhea,* syphilis,*
condyloma acuminatum, chlamydial genital infections*, herpesvirus genital infections, trichomonas vaginitis,
chancroid,* granuloma inguinale, scabies, louse infestation, and bacterial vaginosis (among lesbians). However,
shigellosis,* hepatitis A, B, and C,* amebiasis, giardiasis*, cryptosporidiosis*, salmonellosis,* and
campylobacteriosis may also be transmitted by sexual (oral-anal) contact, especially in homosexual males.
Homosexual contact is a typical method of transmission of HIV, although bidirectional heterosexual transmission is

occurring more commonly (see Infectious Diseases: HIV).
*Reportable to public health authorities.
The risk of developing a sexually transmitted disease following a sexual assault has not been established. Victims
of assault have a high baseline rate of infection (Neisseria gonorrhoeae, 6%; Chlamydia trachomatis, 10%;
Trichomonas vaginalis, 15%; and bacterial vaginosis, 34%), and the risk of acquiring infection as a result of the
assault is significant but is often lower than the preexisting rate (N gonorrhoeae, 6–12%; C trachomatis, 4–17%;
T vaginalis, 12%; syphilis, 0.5–3%; and bacterial vaginosis, 19%). Victims should be evaluated within 24 hours
after the assault, and cultures for N gonorrhoeae and C trachomatis should be obtained. (If culture is not
available, nonculture tests, such as nucleic acid amplification tests, are acceptable. If the test is positive, it must
be confirmed with a second test using a different target sequence.) Vaginal secretions are cultured and examined
for Trichomonas. If a discharge is present, if there is itching, or if secretions are malodorous, a wet mount should
be examined for Candida and bacterial vaginosis. In addition, a blood sample should be obtained for immediate
serologic testing for syphilis, hepatitis B, and HIV. Follow-up examination for sexually transmitted disease should
be repeated within 1–2 weeks, since concentrations of infecting organisms may not have been sufficient to
produce a positive culture at the time of initial examination. If prophylactic treatment was given (see below), tests
should be repeated only if the victim has symptoms. If prophylaxis was not administered, the individual should be
seen in 1 week so that any positive tests can be treated. Follow-up serologic testing for syphilis and HIV infection
should be performed in 6, 12, and 24 weeks if the initial tests are negative. The usefulness of presumptive therapy
is controversial, some feeling that all patients should receive it and others that it should be limited to those in
whom follow-up cannot be ensured or to patients who request it. If therapy is given, a reasonable regimen would
be hepatitis B vaccination (without hepatitis B immune globulin, the first dose given at the initial evaluation and
follow-up doses at 1–2 months and 4–6 months) and one dose of ceftriaxone, 125 mg intramuscularly, plus
file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (22 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
metronidazole, 2 g orally as a single dose, plus doxycycline, 100 mg orally twice daily for 7 days, or azithromycin,
1 g orally as a single dose, instead of doxycycline. In premenopausal women, azithromycin should be used instead
of doxycycline until the pregnancy status is determined; if the pregnancy test is positive, metronidazole should be
given only after the first trimester.
Although seroconversion to HIV has been reported following sexual assault when this was the only known risk, this
risk is believed to be low. The likelihood of HIV transmission from vaginal or anal receptive intercourse when the

source is known to be HIV positive is 1 per 1000 and 5 per 1000, respectively. Although prophylactic antiretroviral
therapy has not been studied in this setting, the Department of Health and Human Services recommends the
prompt institution of postexposure prophylaxis with highly active antiretroviral therapy if the person seeks care
within 72 hours of the assault, the source is known to be HIV positive, and the exposure presents a substantial
risk of transmission.
Golden MR et al: Effect of expedited treatment of sex partners on recurrent or persistent gonorrhea or chlamydial
infection. N Engl J Med 2005;352:676. [PMID: 15716561]

Sexually transmitted diseases treatment guidelines 2002. Centers for Disease Control and Prevention. MMWR
Recomm Rep 2002;51(RR-6):1. [PMID: 12184549]

Smith DK et al: Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational
exposure to HIV in the United States: recommendations from the U.S. Department of Health and Human Services.
MMWR Recomm Rep 2005;54(RR-2):1. [PMID: 15660015]

Infections in Drug Users
Essentials of Diagnosis
● Common infections that occur with greater frequency in drug users include the following: skin infections; hepatitis
A, B, C, D; aspiration pneumonia; tuberculosis; pulmonary septic emboli; sexually transmitted diseases; AIDS;
infective endocarditis; osteomyelitis; and septic arthritis.
● Rare infections in the United States include tetanus, malaria, and melioidosis.
General Considerations
The use of parenterally administered recreational drugs has increased enormously in recent years. There are now
an estimated 300,000 or more injection drug users in the United States.
Common Infections That Occur with Greater Frequency in Drug Users
Skin infections are associated with poor hygiene and use of nonsterile technique when injecting drugs. S
aureus (including methicillin-resistant strains) and oral flora (streptococci, Eikenella,
Fusobacterium, Peptostreptococcus) are the most common organisms, with enteric gram-negatives less common
and seen in those who inject into the groin. Cellulitis and subcutaneous abscesses occur most commonly,
particularly in association with subcutaneous ("skin-popping") or intramuscular injections and the use of cocaine

and heroin mixtures (probably due to ischemia). Myositis, clostridial myonecrosis, and necrotizing fasciitis
occur infrequently but are life-threatening. Wound botulism in association with black tar heroin occurs
sporadically but often in clusters.
Hepatitis is very common among habitual drug users and is transmissible both by the parenteral (hepatitis B, C,
and D) and by the fecal-oral route (hepatitis A). Multiple episodes of hepatitis with different agents can occur.
Aspiration pneumonia and its complications (lung abscess, empyema, brain abscess) result from
altered consciousness associated with drug use. Mixed aerobic and anaerobic mouth flora are usually involved.
file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (23 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
Tuberculosis also occurs in drug users, and infection with HIV has fostered the spread of tuberculosis in
this population. Morbidity and mortality rates are increased in HIV-infected individuals with tuberculosis.
Classic radiographic findings are often absent; tuberculosis is suspected in any patient with infiltrates who does
not respond to antibiotics.
Pulmonary septic emboli may originate from venous thrombi or right-sided endocarditis.
Sexually transmitted diseases are not directly related to drug use, but the practice of exchanging sex for
drugs has resulted in an increased frequency of sexually transmitted diseases. Syphilis, gonorrhea, and chancroid
are the most common.
AIDS has a high incidence among injection drug users and their sexual contacts and among the offspring of
infected women (see Infectious Diseases: HIV).
Infective endocarditis. The organisms that cause infective endocarditis in those who use drugs intravenously
are most commonly S aureus, Candida (especially Candida parapsilosis), Enterococcus faecalis, other
streptococci, and gram-negative bacteria (especially Pseudomonas and Serratia marcescens). A number
of complications of endocarditis can occur, including splenic abscesses, central nervous system infections
(meningitis, brain abscess, subdural empyema, epidural abscess), and endophthalmitis. Involvement of the right
side of the heart is common, and infection of more than one valve is not infrequent. Right-sided
involvement, especially in the absence of murmurs, is often suggested by the presence of septic pulmonary
emboli. The diagnosis must be established by blood culture. Therapy, including empiric treatment, is discussed
in Infectious Diseases: Bacterial & Chlamydial.
Other vascular infections include septic thrombophlebitis and mycotic aneurysms. Mycotic aneurysms
resulting from direct trauma to a vessel with secondary infection most commonly occur in femoral arteries and

less commonly in arteries of the neck. Aneurysms resulting from hematogenous spread of organisms
frequently involve intracerebral vessels and thus are seen in association with endocarditis.
Osteomyelitis and septic arthritis. Osteomyelitis involving vertebral bodies, sternoclavicular joints, the
pubic symphysis, the sacroiliac joints, and other sites usually results from hematogenous distribution of
injected organisms or septic venous thrombi. Pain and fever precede radiographic changes, sometimes by
several weeks. While staphylococci—often methicillin-resistant—are common organisms, Serratia,
Pseudomonas, Candida (usually not Candida albicans), and other pathogens rarely encountered in spontaneous
bone or joint disease are found in injection drug users.
Infections Rare in United States
Tetanus
In the 1950s and 1960s, tetanus was commonly seen in drug users, especially in unimmunized women who
injected drugs subcutaneously ("skin-popping"). Increased tetanus immunization among drug users has resulted in
a decline in this disease, although cases are still reported.
Malaria
Needle transmission occurs from intravenous drug users who acquired the infection in malaria-endemic areas
outside the United States.
Melioidosis
This chronic pulmonary infection caused by Burkholderia pseudomallei occurs occasionally in debilitated drug
users, but most cases are reported in Asia and Australia.
file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (24 of 54) [14/12/2006 8:12:28 μμ]
AccessMedicine - Print
Treatment
A common and difficult clinical problem is management of the parenteral drug user who presents with fever.
In general, after obtaining appropriate cultures (blood, urine, and sputum if the chest radiograph is
abnormal), empiric therapy is begun. If the chest radiograph is suggestive of a community-acquired
pneumonia (consolidation), therapy for outpatient pneumonia is begun with a third-generation cephalosporin, such
as ceftriaxone, 1–2 g intravenously every 24 hours (many clinicians would add azithromycin, 500 mg orally
or intravenously every 24 hours, or doxycycline, 100 mg orally or intravenously twice daily, to this regimen). If
the chest radiograph is suggestive of septic emboli (nodular infiltrates), therapy for presumed endocarditis
is initiated, usually with a combination of vancomycin 15 mg/kg every 12 hours intravenously (due to the

high prevalence of methicillin-resistant S aureus and the possibility of enterococcus) and gentamicin, 1 mg/kg
every 8 hours intravenously. If the chest radiograph is normal and no focal site of infection can be found,
endocarditis is presumed. While awaiting the results of blood cultures, empiric treatment with vancomycin
and gentamicin is started. If blood cultures are positive for organisms that frequently cause endocarditis in
drug users (see above), endocarditis is presumed to be present and treated accordingly. If blood cultures are
positive for an organism that is an unusual cause of endocarditis, evaluation for an occult source of infection
should go forward. In this setting, a transesophageal echocardiogram may be quite helpful since it is 90% sensitive
in detecting vegetations and a negative study is strong evidence against endocarditis. If blood cultures are
negative and the patient responds to antibiotics, therapy should be continued for 7–14 days (oral therapy can
be given once an initial response has occurred). In every patient, careful examination for an occult source of
infection (eg, genitourinary, dental, sinus, gallbladder) should be done.
Gordon RJ et al: Bacterial infections in drug users. N Engl J Med 2005;353:1945. [PMID: 16267325]

Infections in injection drug users (entire issue). Infect Dis Clin North Am 2002;16:3.

Acute Infectious Diarrhea
Essentials of Diagnosis
● Arbitrarily divided into acute and chronic and mild, moderate, and severe.
● Diarrhea is acute if lasts < 2 weeks and chronic if lasts > 2 weeks.
● Disease is mild if there are three or fewer stools per day, moderate if there are four or more stools in association
with local symptoms (abdominal cramps, nausea, tenesmus), and severe if there are four or more stools per day
with systemic symptoms (fevers, chills, dehydration).
General Considerations
Acute diarrhea can be caused by a number of different factors, including emotional stress, food intolerance,
inorganic agents (eg, sodium nitrite), organic substances (eg, mushrooms, shellfish), drugs, and infectious
agents (including viruses, bacteria, and protozoa). From a diagnostic and therapeutic standpoint, it is helpful
to classify infectious diarrhea into syndromes that produce inflammatory or bloody diarrhea and those that
are noninflammatory, nonbloody, or watery. In general, the term "inflammatory diarrhea" suggests
colonic involvement by invasive bacteria or parasites or by toxin production. Patients complain of frequent
bloody, small-volume stools, often associated with fever, abdominal cramps, tenesmus, and fecal urgency.

Common causes of this syndrome include Shigella, Salmonella, Campylobacter, Yersinia, invasive strains
of Escherichia coli, E coli O157:H7, Entamoeba histolytica, and C difficile. Tests for fecal leukocytes or the
neutrophil marker lactoferrin are frequently positive, and definitive etiologic diagnosis requires stool
culture. Noninflammatory diarrhea is generally milder and is caused by viruses or toxins that affect the
file:///C|/Documents%20and%20Settings/Admini fectious%20Diseases%20General%20Problems.htm (25 of 54) [14/12/2006 8:12:28 μμ]