Page 411 - Williams Hematology ( PDFDrive )

386 Part V: Therapeutic Principles Chapter 24: Treatment of Infections in the Immunocompromised Host 387

P. jiroveci pneumonia may be treated with trimethoprim-sul- are associated with poor prognoses. The prevalence of multidrug-resis-
famethoxazole. Pentamidine or primaquine-clindamycin should be used tant tuberculosis varies tremendously by country. Drugs used to treat
91
for moderate to severe infections in patients who are allergic to or oth- multidrug-resistant tuberculosis include fluoroquinolones, amikacin,
erwise intolerant of trimethoprim-sulfamethoxazole, although data for capreomycin, and kanamycin. Extensively drug-resistant M. tuberculo-
alternative regimens is much more robust in the HIV-positive patient sis, which is defined as being resistant to rifampin, isoniazid, fluoro-
74
population. Other alternative regimens include dapsone-trimethoprim quinolones, and at least one injectable second-line agent, is a potentially
and atovaquone, although these are best used for mild PCP. Glucocorti- a huge clinical problem. 92
coids are commonly given as adjunctive treatment in severe PCP, though Although relatively uncommon, nontuberculous mycobacterial
the data for this among non–HIV-infected patients are conflicting. 75 infections also occur in patients with hematologic malignancy. Myco-
Empiric therapy with antifungal agents is currently the standard of bacterium avium-intracellulare complex is treated with clarithromycin,
care in high-risk neutropenic patients with persistent fever. However, rifabutin, and ethambutol. Treatment of infections with rapidly growing
preemptive antifungal treatment is being evaluated as a possible alter- mycobacteria is complicated and should be guided by an infectious dis-
native to empiric therapy in select patients. With preemptive strategies, ease specialist. 13
microbiologic, molecular, and radiologic monitoring is used to detect Table 24–1 lists the drugs used as empiric therapy in neutropenic
early evidence of invasive fungal infections and prompt initiation of patients.
76
therapy. Data from studies comparing empiric therapy with preemp-
tive strategies are mixed. 77–79 Surveillance with fungal cell wall compo- ADJUSTING THERAPY
81
80
nents 1,3-β-D-glucan and galactomannan in the blood plays a role in
preemptive therapy. Real-time polymerase chain reaction of fungal gene Adjustment or modification of the initial antimicrobial regimen may be
products is another technique that appears to have high sensitivity and necessary for several reasons. Results of cultures may suggest another
specificity for detecting candidemia, although it will require standard- regimen would be more active or less toxic. All cultures may remain
ization before widespread use is possible. 82 negative while the patient fails to respond to the regimen. Fever may
Although currently not as large a problem as drug-resistant bac- recur following an initial response to therapy, raising the possibility of
teria, the development of drug-resistant fungal organisms is a poten- a second infection.
tial clinical threat. Prophylactic use of antifungals likely contributes to Adjusting therapy based on a culture report usually is straight-
83
breakthrough infection with innately resistant species. Cross-resis- forward, but the other two situations may pose dilemmas. In these cir-
tance within and between classes of antifungals is another potentially cumstances, resistant organisms or noninfectious causes of fever, such
important problem, which is deserving of clinical study. 84 as drug fever or recurrence of malignancy, must be considered. Repeat
cultures and careful clinical reappraisal may prove helpful.
Viral Infections
A limited number of options are available for treatment of viral infec- DURATION OF THERAPY
tions. Acyclovir is active against herpes simplex and, at higher doses, Antibiotic therapy for a specific infection is commonly continued for
against varicella zoster. Other agents, such as famciclovir and valacyclo- a defined minimum period of time and until the granulocyte count
vir, are as effective in treating herpes simplex and zoster infections, and reaches 0.5 × 10 /L. Although this strategy reduces the number of
9
may be administered less frequently, but are not available for intrave- relapsing infections, it may increase the risk of superinfection and
nous administration. 85 antibiotic toxicity. In low-risk patients whose fever resolves without a
Ganciclovir, valganciclovir, and foscarnet have efficacy in treat- documented source of infection, empiric intravenous therapy can usu-
ment of CMV disease and are also active against herpes simplex. They ally be stopped and replaced by an oral regimen until counts recover.
86
are most effective when they are used early in the course of the infection. Alternatively, there is some evidence that returning to a prophylactic
Hence, frequent screening for CMV and early preemptive treatment in regimen in select patients before the absolute neutrophil count reaches
high-risk patients, such as transplant recipients, may allow for improved 0.5 × 10 /L is also a reasonable approach. If antibiotics are discontin-
93
9
87
outcomes. Ganciclovir or valganciclovir is usually the first-line therapy ued or deescalated, close observation is required, and therapy should be
against CMV, but results in marrow suppression in a significant per- reinstituted at any suggestion of recurrent infection.
centage of patients who receive them. Foscarnet, a second-line agent,
may be complicated by azotemia and electrolyte abnormalities. FEVER FOLLOWING RECOVERY FROM
Ribavirin plus an adjunctive immunomodulator such as RSV
immunoglobulin (Ig) or intravenous immunoglobulin (IVIG) are used CHEMOTHERAPY
to treat RSV pneumonia in immunocompromised patients. Ribavirin Fevers occasionally persist or even begin after the granulocyte count has
can also be used to treat RSV upper respiratory tract infections, and returned to normal levels. Drug fever and engraftment syndrome are
may prevent spread to the lower respiratory tract as well as decrease considerations in this setting, although a deep-seated infection must be
mortality; however, prospective studies are needed. The optimal route excluded. Hepatosplenic candidiasis is one important consideration in
88
94
of ribavirin administration (oral versus inhaled) is not yet known. Osel- these patients, although its incidence has likely decreased in the setting
tamivir or zanamivir should be used if influenza A is suspected. 89 of widespread antifungal prophylaxis discussed under “Fungal Infec-
tions” below. Elevated serum alkaline phosphatase levels and the pres-
95
Mycobacterial Infections ence of multiple “punched-out” lesions in the liver on CT are common
Rates of Mycobacterium tuberculosis infection are high among patients findings with hepatic involvement. Blood cultures are frequently nega-
96
with hematologic malignancy worldwide, and tuberculosis should be tive so biopsy may be required to establish a microbiologic diagnosis.
ruled out in neutropenic patients with lung infiltrates who have tuber- Hepatosplenic candidiasis requires prolonged therapy. Several regimens
97
98
culosis risk factors. First-line therapy for tuberculosis includes rifam- have been proposed, including fluconazole, caspofungin, and liposo-
pin, isoniazid, pyrazinamide, and ethambutol. 90 mal amphotericin B, but there are no randomized trial data. Persistent
99
Infections with multidrug-resistant tuberculosis, defined as symptoms despite treatment may be a result of immune reconstitution
microbes resistant to rifampin and isoniazid, are difficult to treat and inflammatory syndrome and may be relieved by adjuvant treatment

Kaushansky_chapter 24_p0383-0392.indd 386 9/17/15 5:57 PM