Page 1633 - Hematology_ Basic Principles and Practice ( PDFDrive )

1454 Part VIII Comprehensive Care of Patients with Hematologic Malignancies

time period. The propensity of viridans streptococci to develop
Approach to Pulmonary Infiltrates
resistance to quinolones and gram-negative bacilli to be resistant to
Pulmonary infiltrates can be divided into three general categories: quinolones and β-lactams means that there is no perfect preventive
consolidative, interstitial, and nodular. A consolidative infiltrate may regimen.
be bacterial, even polymicrobic, so sampling of the infiltrate through Central venous catheter placement through the skin can lead to
sputum or endotracheal tube suctioning for bacterial and fungal blood infection from colonizing gram-positive skin organisms, despite
cultures is required. If either of these methods does not provide an sterile, operative placement of these catheters and antisepsis cleansing
adequate sample from a consolidative infiltrate, or if these methods procedures. Because the gram-positive bacteremias, including those
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do not lead to a diagnosis, “early” (within 72 hours) bronchoscopy caused by coagulase-negative Staphylococcus species, usually are not
is indicated. If interstitial or nodular infiltrates are not peripheral (i.e., immediately life threatening, direct prophylactic coverage often is not
within the range of the bronchoscope), they should also be evaluated immediately provided. During workup of a new fever, some treat-
with timely bronchoscopy. An advantage of bronchoscopy, in addition
to the ability to obtain a deep specimen, is that the samples usually ment guidelines advocate the administration of vancomycin for
are sent for a broad range of diagnostic tests. These tests usually several days until blood cultures demonstrate no gram-positive bac-
are ordered from preprinted order sheets, which reduce errors. Most teremia. The use of antimicrobial-coated bloodstream catheters can
preprinted order sheets for bronchoalveolar lavage fluid will test for be effective in reducing rates of catheter-related bloodstream
the following: infections.
• Cytology, with the attendant Fite and Gomori methenamine silver Once a gram-positive bacterial infection is identified, vancomycin
stains therapy is often used empirically until the susceptibility profile is
• Bacterial (Gram) stain and aerobic culture available and targeted therapy can be provided. There are concerns
• Mycobacterial (acid-fast bacillus) stain and culture about the efficacy of vancomycin in treating serious S. aureus infec-
• Fungal (potassium hydroxide or calcofluor) stain and culture
• Nocardia culture tions because of relative or frank vancomycin resistance. Similarly, if
• Legionella culture the patient is known to be colonized with vancomycin-resistant
• Viral cultures for herpes viruses and respiratory viruses enterococcus and the Gram stain indicates gram-positive organisms
• Rapid test for cytomegalovirus (shell vial or polymerase chain in chains, therapy for empiric vancomycin-resistant enterococcus is
reaction [PCR]) appropriate until the bacterial identification and susceptibility profile
• Rapid test for respiratory viruses during respiratory virus season is available, usually with daptomycin or linezolid.
(pooled respiratory virus shell vial, respiratory syncytial virus Once a gram-negative infection is identified, empiric therapy
antigen, influenza A/B antigen) that includes Pseudomonas coverage is continued until the suscep-
Optional tests that can be requested from bronchoalveolar lavage tibility profile is available. In the severely neutropenic host, serious
fluid, some at significant extra expense, include the following:
• Mycobacterial stain (requires separate 5 mL volume that cannot gram-negative infections are often treated with combination therapy
be used later for culture) consisting of a β-lactam plus either an aminoglycoside or a quino-
• Mycoplasma pneumoniae PCR lone depending on the antimicrobial sensitivity pattern and patient
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• Chlamydia pneumoniae PCR comorbidities. However, data demonstrating the superiority of
• Human herpesvirus type 6 PCR combination therapy over β-lactam monotherapy are lacking. The
• Human metapneumovirus PCR emergence of extended-spectrum β-lactamase producing gram-
• Aspergillus galactomannan antigen negative bacilli is a particular concern in patients with significant
• Any of the above first-tier tests that your institution does not send antimicrobial exposure as are the development of infections with
on a routine basis (e.g., Nocardia or Legionella) pan-resistant organisms, such as multidrug-resistant Acinetobacter
Invasive sampling may be the only definitive means for making a
diagnosis of peripheral nodules. The two main options are percutaneous baumannii (see box on Treatment of Drug-Resistant Gram-Negative
fine-needle aspiration or open lung biopsy (usually obtained through Bacilli). For many infections, the regimen then can be tailored to
video-assisted thoracoscopic surgical procedure). In toto sampling of a a single agent and continued for 2 weeks after the last positive
lung nodule permits enough material for the whole range of the above culture in clinically responding patients. Therapy with a carbapenem
diagnostic tests as well as histopathology. Of note, fewer lobectomies resistant to β-lactamase hydrolysis is required if an organism is iso-
of unilateral pulmonary nodular infiltrates have been reported in recent lated that is known to have an inducible β-lactamase enzyme (e.g.,
years, probably a result of the frequent use of a broad range of less Enterobacter).
toxic antifungal medications. For bloodstream infections, repeat blood cultures should be drawn
after 2 to 3 days of effective therapy to ensure that sterilization of the
bloodstream has been achieved. Persistently positive blood cultures
suggest the development of a deep-seated or endovascular site of
Bacteria infection such as infective endocarditis or suppurative thrombophle-
bitis. When a bloodstream catheter is proven to be the source of the
Because bacterial infections cause significant morbidity and mortality infection, 12,18 removal of the catheter may be required for most, but
in neutropenic patients, broad-spectrum antibacterial prophylaxis is not all, infections. At the end of a 14-day treatment course beyond
often used during periods of profound neutropenia. The exact agents the last positive culture, the patient should be transitioned to an oral
used vary, but typical agents include a quinolone (e.g., levofloxacin) gram-negative prophylaxis regimen if still neutropenic.
or a β-lactam (e.g., cefpodoxime). Institutional protocols and resis- Antimicrobial agents with anaerobic activity should be added for
tance patterns drive selection of specific prophylactic agents. Oral neutropenic enterocolitis, enlargement of neck soft tissues during
prophylaxis regimens are generally discontinued and substituted with mucositis (Ludwig angina variant), or culture-documented anaerobic
intravenous antibacterials with enhanced activity against Pseudomonas infection. Infrequently, tuberculous and nontuberculous mycobacte-
aeruginosa with the first onset of fever. The use of oral antibiotics ria are responsible for infections in the bloodstream, catheters, and
among low-risk, neutropenic patients with fever is guided by the use pulmonary tree. Infections of central catheters or catheter tunnels
of standardized scoring systems (e.g., MASCC index). 1 caused by rapidly growing atypical mycobacterial infections require
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Mucositis, with breakdown of oral and GI mucosal barriers, is a high index of suspicion, as well as specific culture media. Organ-
common during this period. This condition can predispose to sepsis ism identification and drug sensitivities may take several weeks.
from bacterial and fungal organisms that typically colonize the GI Tuberculous disease can be empirically treated based on risk factors.
tract. The most common serious infections occurring in neutropenic For patients without risk factors for tuberculosis, recovery of acid-fast
patients with mucositis are bacteremias due to viridans group strep- bacilli will prompt therapy for suspected nontuberculous mycobac-
tococci and gram-negative bacilli. Such infections are particularly teria, usually with clarithromycin and either a quinolone or etham-
common during the first several weeks following HSCT, so broad- butol until specific susceptibility information is available. Tailored
spectrum antimicrobial prophylaxis is generally given during this therapy is often continued for a minimum of 3 to 6 months.