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384 Part V: Therapeutic Principles Chapter 24: Treatment of Infections in the Immunocompromised Host 385

immunocompromised hosts, herpes simplex, varicella zoster, cytomeg- an indwelling urinary catheter, those whose urinalysis is suspicious
alovirus (CMV), and adenoviruses are the most important. Cutaneous for infection, and those who have urinary symptoms. Sputum cultures
lesions and mucositis often are caused by herpes simplex. Herpes zoster may be helpful in patients with respiratory symptoms or findings on
infections may be especially severe and have a propensity for dissemi- chest radiographs, but must be interpreted with caution, because the
nation. Left untreated, primary varicella infections are associated with results may reflect the flora colonizing the oropharynx rather than the
a high mortality rate. CMV may cause febrile illnesses associated with pathogens infecting the lung. Pulmonary fungal and viral infections,
pneumonia, hepatitis, and/or gastrointestinal tract ulcerations. Respira- which may be difficult to document using conventional culture tech-
tory syncytial virus (RSV) and influenza virus are important pathogens niques, may be diagnosed by polymerase chain reaction and antigen
causing respiratory illness in stem cell transplant recipients in the win- detection sent from nasal washes or bronchoalveolar lavage samples. 19,20
ter months. Virus-associated hemorrhagic cystitis caused by BK virus Skin lesions of a suspicious nature should be biopsied and cultured.
9
and adenovirus is common among hematopoietic stem cell transplant Stool should be cultured as well as examined for ova and parasites, and
recipients. 10 Clostridium difficile in patients with diarrhea. In some patients, testing
for rotavirus, norovirus, and adenovirus also may be appropriate.
MYCOBACTERIAL PATHOGENS Patients with findings on chest CT that are consistent with pneu-
The association between lymphoid malignancies and tuberculosis, par- monia who do not respond to initial therapy and in whom initial micro-
biologic testing is negative may benefit from transbronchial biopsy or
ticularly among patients born outside the United States, has been recog- CT-guided biopsy of affected tissue. 21
nized for more than a century. It threatens to become a more frequent,
serious problem with the resurgence of tuberculosis and the increased
prevalence of drug-resistant strains. 11,12 Nontuberculous mycobacterial TREATMENT AND PREVENTION
infections are common in HIV-positive patients, but are less common
in patients receiving chemotherapy. 13 INITIAL TREATMENT
Bacterial Infections
RECOGNITION AND DIAGNOSIS OF Many different regimens have been evaluated and found to be acceptable
INFECTION for empiric therapy in febrile patients with neutropenia. Current rec-
ommendations support single-drug therapy with an antipseudomonal
The development of an infection in a neutropenic patient may be β-lactam as initial empiric therapy in febrile neutropenic patients.
22
accompanied by dramatic clinical manifestations or by none at all. Piperacillin-tazobactam, imipenem, meropenem, cefepime, and
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Any fever that develops is very suggestive of infection. However, hypo- ceftazidime have each been studied as a single agent. These drugs are
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thermia, declining mental status, myalgia, or lethargy also may indicate active against most of the virulent pathogens infecting neutropenic
infection in these patients. The usual local signs of infection, such as patients. Doripenem, another carbapenem with antipseudomonal
pus formation, may be absent or delayed because they are mediated by activity has not been studied in a prospective randomized control trial
neutrophils. 14 in febrile neutropenia. Ertapenem, a carbapenem that is attractive for its
A careful physical examination should be performed when such a daily dosing schedule, lacks activity against pseudomonas and should
change in condition is observed. Special attention should be paid to the not be used as empiric therapy. Differences in institutional sensitivity
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mouth and teeth for evidence of thrush, ulcerations, or periodontal dis- patterns should guide initial antibiotic selection, which should subse-
ease. The skin should be examined in detail. Innocuous-appearing skin quently be tailored to culture results.
lesions may be septic emboli or evidence of disseminated fungal infec- Although Gram-negative coverage with a single agent is associated
tion. Ordinarily trivial injuries inflicted by venipuncture or intravenous with improved outcomes, among patients who are unstable or in whom
29
catheters may become infected and result in sepsis. An increased inci- antibiotic resistance is suspected, it is reasonable to add a second anti-
dence of perianal and perirectal infection is observed in neutropenic biotic active against Gram-negative organisms. Aminoglycosides may
patients. Examination of the rectum and perineum may provide a provide synergy against Gram-negative bacilli and further broaden the
15
clue to the source of fever in patients without other clinical findings. spectrum of antimicrobial activity, but they increase the risk of neph-
Although such examinations should not be performed unnecessarily on rotoxicity. No good evidence supports the simultaneous use of two
an immunocompromised patient, rectal or pelvic examination should β-lactam drugs. Fluoroquinolones in conjunction with another antibiotic
not be deferred when searching for a cause of fever. are effective in patients who have not received quinolone prophylaxis. 30
Chest radiographic films should be obtained initially and may Patients with catheters, patients presenting with sepsis, patients
need to be repeated, although this practice has been questioned in with evidence of skin or soft-tissue infection, and other high-risk
patients without respiratory complaints. Chest computed tomography patients should be treated empirically for Gram-positive infections with
16
(CT) may reveal lesions not detected on routine radiograms. Addi- vancomycin. Among patients without these risk factors, Gram-positive
17
tional imaging should be guided by clinical presentation. coverage should be added if fever persists for more than 3 to 5 days after
Blood cultures should be collected prior to initiation of antibiotic Gram-negative treatment is initiated. 22
therapy, and periodically thereafter if fever persists. If an indwelling The emergence of multidrug-resistant organisms has influenced
venous catheter is present, a blood culture as well as cultures from each the approach to empiric therapy. Approximately 60 percent of the
lumen of the catheter should be obtained for bacterial and fungal patho- hospital-acquired strains of Staphylococcus aureus now are methicil-
gens. Differential time to positivity of central and peripheral cultures lin-resistant S. aureus (MRSA), as are a growing number of community
may be helpful in diagnosing catheter-associated infections. Sending -acquired strains. Vancomycin, quinupristin/dalfopristin, linezolid,
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two or three cultures improves the likelihood of recovering fastidious daptomycin, ceftaroline, and tigecycline are active against MRSA.
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organisms. If differential time to positivity cannot be performed, poten- However, it should be noted that daptomycin should not be used in
tially infected intravenous lines should be cultured upon removal. pneumonia because of inactivation by surfactant. Tigecycline should
Other cultures should be obtained based on presenting symp- be avoided in bloodstream infections because of inadequate serum lev-
toms and risk factors. Urine cultures should be sent in patients with els, and the drug now carries a black box warning because of increased

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