Page 1634 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 89 Clinical Approach to Infections in the Compromised Host 1455

alveolar hemorrhage associated with parainfluenza virus infection has
Treatment of Drug-Resistant Gram-Negative Bacilli
been sporadically reported following transplantation.
The widespread use of antibiotic prophylaxis among immunocom- Patients with lymphopenia are susceptible to a range of herpes
promised patients has been associated with the development of virus family infections. Herpes simplex reactivation infections
antimicrobial drug resistance, which is especially problematic among typically manifest as oral or genital ulcers, although more widespread
gram-negative bacilli. Drug-resistant organisms can colonize the GI involvement can occur, and are treated with low doses of acyclovir
tract for prolonged periods of time and emerge to cause serious adjusted for renal function (e.g., 5 mg/kg IV every 8 hours) or
infections during periods of neutropenia or other medical stress (e.g., oral valacyclovir (1 g bid). Reactivation of VZV can be severe in
following admission to the intensive care unit). immunosuppressed persons and is treated with higher doses of
• Pseudomonas aeruginosa is the paradigm for drug resistance acyclovir (e.g., 10 mg/kg IV every 8 hours or oral valacyclovir, 1 g
among gram-negative bacilli and often rapidly develops pan- three times a day). Use of acyclovir to prevent reactivation of HSV
resistance to antimicrobials. Serious pseudomonal infections
are generally treated with two antimicrobial agents, although will also prevent VZV reactivation. Because many patients have not
convincing data supporting this approach are lacking. been exposed to acyclovir chronically (except for patients previously
• Extended-spectrum β-lactamase (ESBL) production among treated with recurrent courses of acyclovir for frequent outbreaks of
Enterobacteriaceae such as Escherichia coli and Klebsiella genital herpes), there is little reason to expect resistance to acyclovir.
pneumoniae renders these organisms resistant to non- However, HSV infections that appear or persist through acyclovir
carbapenem β-lactam antibiotics. Treatment is generally with prophylaxis should be considered acyclovir resistant until viral
a carbapenem (e.g., meropenem), although a quinolone can sensitivity testing can be performed, and consideration should be
sometimes be used. given to initiating treatment with foscarnet or cidofovir. Reports
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• The presence of a Klebsiella pneumoniae carbapenemase of acyclovir-resistant varicella are extremely rare. Foscarnet infusions
(KPC) can occur among species other than K. pneumoniae
and creates resistance to all β-lactam antibiotics including affect calcium homeostasis, so monitoring of ionized calcium and
carbapenems. Resistance to quinolones is also typical, so therapy phosphorus levels is required during clinical use of the drug. The
is limited to the polymyxins (e.g., colistin), or to tigecycline and major side effect of cidofovir is renal toxicity, which can be reduced
the aminoglycosides depending on the organism’s antibiotic to some degree with probenecid and hydration. Clinically significant
susceptibility pattern. CMV infection can occur during neutropenia, but the antigenemia
• Like P. aeruginosa, A. baumannii can develop resistance to all test cannot be used for diagnosis or monitoring of response to
known antimicrobials via a variety of mechanisms. This generally therapy in this situation, so DNA PCR methods are preferred in that
occurs among critically ill patients following prolonged stays in the setting.
intensive care unit. Treatment options may include polymyxins Human herpesvirus type 6 (HHV-6) is ubiquitous, and reactiva-
and sulbactam, a β-lactamase inhibitor that possesses some
activity against drug-resistant Acinetobacter. tion commonly occurs in patients with significant immunosuppres-
• Enterobacter, Serratia, and Citrobacter species can elaborate an sion. However, clinically significant disease due to HHV-6 occurs in
AmpC β-lactamase following initiation of β-lactam therapy, which only a small percentage of patients who have HHV-6 detected in their
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can result in a relapsing infection following an initial response. blood. HHV-6 infection can manifest as fever or pancytopenia.
Thus clinicians treating such infections with penicillins or Other recognized clinical syndromes include pneumonitis and
cephalosporins should closely monitor patients for the emergence encephalitis. Infection is diagnosed by quantitative PCR, although
of resistance. If resistance does emerge, AmpC-producing the exact levels of virus that indicate clinically significant disease are
organisms can be treated with a carbapenem. not known. Detection of virus in the first 3 weeks following trans-
• Patients with multidrug-resistant gram-negative infections should plantation may be associated with early skin maculopapular rash and
be cared for in such a manner as to minimize spread of these
dangerous organisms to other patients. Compliance with infection acute GVHD, but it can also present without overt clinical symptoms.
control protocols is paramount. Prospective large-scale studies are needed to determine the role of
• Knowledge of the local epidemiology and antibiogram are HHV-6 infection. HHV-6 has 60% DNA homology with CMV, and
important for preemptive and empiric antibiotic choices, treatment of documented infection usually is initiated with induction
especially against gram-negative rods. doses of foscarnet or ganciclovir. Responses to antiviral therapy are
• A carefully designed and executed antibiotic stewardship program not universal, and benefits of foscarnet versus ganciclovir have not
could curtail unnecessary antibiotic use, thereby decreasing been determined.
antibiotic selection pressure with a resulting decrease in bacterial Cidofovir, when combined with aggressive supportive measures,
resistance rates.
is considered an adjunct in treatment of BK and adenovirus-associated
hemorrhagic cystitis. Similarly, cidofovir can be used to treat dis-
seminated adenovirus infections typically three times a week at 1 mg/
kg/day, along with probenecid and hyperhydration.
Viruses
Neutropenia per se is not a major risk factor for developing viral Fungi
infections but concomitant lymphopenia is common and does pre-
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dispose to infections with a range of viruses. Respiratory virus Most yeast infections in immunosuppressed patients are caused by
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infections are seasonal, except for parainfluenza. A frequent pathogen Candida. Candidal organisms that colonize the mouth and gut
with clinical significance is respiratory syncytial virus, although proliferate when antibacterial agents suppress the coexisting bacterial
influenza, parainfluenza, adenovirus, enteroviruses, the herpesviruses flora population. Guidelines for the treatment of candidiasis have
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(including HHV-6), human metapneumovirus, and rhinovirus also been issued. Patients who are clinically stable generally can be
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produce diffuse interstitial infiltrates and pneumonitis. HHV-6 and treated with fluconazole unless there has been previous azole exposure
human metapneumovirus are not recovered with the usual tests or mold infection is also a concern. Unstable patients or those who
ordered at the time of bronchoscopy, so a high suspicion for infection have been receiving an azole are usually treated with an echinocandin.
is required to order specific PCR testing. Documented infection with Prevention of candidemia among allogeneic HSCT recipients is
RSV prompts contact and droplet isolation precautions. Treatment generally achieved with fluconazole. However, fluconazole does not
components may include aerosolized ribavirin, IVIg, and in some have activity against some nonalbicans Candida species (e.g., C.
cases, monoclonal antibody therapy. However, proof of efficacy of glabrata, C. krusei) and all molds (e.g., Aspergillus, Fusarium, the
these treatments remains elusive, and the disease can cause significant Mucorales species). Among patients colonized with yeast species
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morbidity and mortality. With respiratory syncytial virus infections, other than C. albicans and among heavily pretreated patients who
aerosolized ribavirin treatment appears safe, and trends of decreasing may have incubating mold infection, prophylaxis using a mold-active
viral loads have been reported. Secondary graft failure or diffuse triazole (e.g., posaconazole) or an echinocandin is preferred. 26