In patients with possible gram-positive infections, vancomycin is effective initial treatment. It provides adequate coverage for the most common organisms such as staphylococci, streptococci, and most enterococci; however Enterococcus faecium can be resistant to vancomycin. The rates of this resistance vary from one institution to another, but may be as high as 90%. Enterococcus faecalis is much less likely to have vancomycin resistance. For patients with vancomycin-resistant organisms or vancomycin allergy, alternative agents include daptomycin or linezolid. Daptomycin is effective in staphylococcal bacteremia and serious skin and soft-tissue infection. Its main side effect is elevation of creatinine phosphokinase (CPK) and muscle damage; thus monitoring of CPK is warranted. Linezolid is approved for skin and soft-tissue infections but should not be used for bloodstream infections. Its major side effects of bone marrow suppression and optic neuritis limit its usefulness.

Duration of treatment for gram-positive organisms varies based on the type of infection. In general these organisms do not result in the sepsis syndrome and early mortality but may lead to significant complications if not treated appropriately. Infections of the skin and soft tissue require at least 7 days of therapy with adequate debridement when indicated. Bacteremia due to S. aureus may require up to 4 weeks of therapy if the source is not located or if the bacteremia does not resolve quickly, whereas enterococcal and coagulase-negative staphylococcal infections can be treated for shorter durations, especially if infected catheters are removed. If gram-positive coverage was added empirically, it may be stopped after 2 days if no evidence of gram-positive infection is found.

Anaerobes

Anaerobes can cause infections in neutropenic patients as a result of mucosal damage. Anaerobic coverage is warranted in patients with significant abdominal complaints while awaiting cultures. This includes coverage for Bacteroides spp. and Prevotella spp. Acceptable antibiotics include a β-lactam/β-lactamase combination, carbapenem, tigecycline, or addition of metronidazole to other regimens.

Clostridium difficile colitis is always a concern in someone who develops diarrhea while on antibiotics. In addition, some cancer chemotherapeutics have antimicrobial activity and C. difficile has been reported in patients who have not received an antibiotic. Any antibiotic can result in C. difficile diarrhea. What complicates the picture is that chemotherapeutic agents can lead to diarrhea because of mucositis. When a patient develops significant diarrhea and abdominal pain while receiving antibiotics, empiric metronidazole or oral vancomycin is warranted while awaiting the toxin assay results. An important part of C. difficile treatment includes stopping the agent that led to the diarrhea in the first place; unfortunately, that is not likely to be feasible in these patients because of the concern for other infections. Since the early 2000s there has been an increase in severe C. difficile diarrhea. There are epidemic strains of C. difficile that can lead to severe colitis resulting in colon perforation and emergent surgical intervention. This change in severity is believed to be due to overproduction of C. difficile toxin. Therapy still includes metronidazole or oral vancomycin; however, close monitoring for complications is necessary.

Fungi

Fungal infections are increasingly common among patients with neutropenia and especially those with acute leukemia or lymphoma as they can remain neutropenic for prolonged periods of time. Some reasons for the increased risk of infection include longer survival in patients with bacterial infections, chronic indwelling catheters, mucosal breakdown, parenteral nutrition, and prolonged antibiotic therapy (Table 85.2).

Candida spp. are the most common cause of fungal infections in these patients and one of the leading causes of catheter-associated bloodstream infections. Candida also cause disseminated disease involving organs such as the liver and spleen. Disseminated candidiasis may be difficult to diagnose by blood cultures alone because they are only 70% sensitive. In patients with prolonged neutropenia and fever, imaging of the abdomen, with attention to the liver and spleen, to look for disseminated fungal infection is necessary. Yeast and molds typically are not the cause of initial fever in neutropenic patients but rather present with persistent or recurrent fever in those already receiving antibiotics. Empiric antifungal therapy and investigation for fungal infection should be considered for patients who remain febrile after 4 to 7 days of appropriate antibacterial therapy or those who received antimicrobial prophylaxis.

Therapy for Candida bloodstream infection includes removal of any indwelling catheter to help clear the organism from the bloodstream. In addition, ophthalmologic exam is necessary after therapy to make sure the patient did not develop endophthalmitis, a rare complication of candidemia. Candida spp. have variable resistance to available agents, and appropriate choice in antifungals is critical. Multiple agents are available for treatment of Candida and include the azoles, echinocandins, and polyenes. The traditional therapy with amphotericin B is uncommonly used because of adverse events such as infusion reactions and nephrotoxicity. The lipid formulations of amphotericin are also not used frequently for Candida infections because of cost and the availability of good alternative agents.

The triazole

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