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Anaerobes: not to be forgotten in neutropenic fever

In the modern era of multidrug-resistant gramnegative bacilli (MDR GNB) and vancomycinresistant enterococci (VRE), and increasing minimum inhibitory concentration (MIC) values to penicillin in streptococcal isolates and to vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) isolates, the role of anaerobic bacteria in the etiology of neutropenic fever can be overlooked. The case report by Haussen et al. [1] in this issue highlights the serious outcomes that can occur in anaerobic bacterial sepsis in a neutropenic patient. Although Clostridium subterminale is one of hundreds of anaerobic bacteria, this case acts as an important reminder that the spectrum of antimicrobial cover in the treatment of patients with neutropenic fever who remain unstable despite antimicrobial therapy must be broadened to include anaerobic pathogens. Anaerobic bacteria are widely distributed in the environment and can be part of the normal flora of the skin, mucosal surfaces, and gastrointestinal tract. Anaerobic pathogens have been found to cause bacteremia in around 1–17% of positive blood cultures [2]. Although the rates of isolation fluctuate between centers and over time, in all series anaerobes make up a small but significant contribution to bacteremia [3,4]. Patient groups predisposed to anaerobic infections are those with underlying acute leukemia, and genitourinary and gastrointestinal malignancies [2]. Anaerobic infections should be further considered in those patients with clinical features such as abdominal symptoms, peri-rectal abscesses, or rapidly progressive soft tissue infections. Many of these infections are polymicrobial. Anaerobes and gram-negative organisms also predominate in neutropenic enterocolitis. The utility of routine anaerobic blood cultures has long been the subject of debate; however, reports now largely recommend that both aerobic and anaerobic blood cultures be collected routinely, especially in at-risk populations. The recently published Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of neutropenic fever recommend the collection of both aerobic and anaerobic blood cultures from all central venous catheter lumens, when present, and from a peripheral vein [5]. Bacteroides fragilis is the most frequent anaerobe isolated from blood cultures, followed by other Bacteroides spp. and Clostridium spp. [3,6]. Other anaerobes commonly causing bacteremia include: anaerobic gram-positive cocci (including Preptostreptococcus spp.), Fusobacterium spp., and Prevotella spp. One of the largest studies of anaerobic bacteremia [7,8] showed cure rates of 70% for patients with non-sporulating aerobic infections (especially B. fragilis), and 58% for patients with clostridial infections (predominantly C. perfringens and C. septicum). A review in patients with hematopoietic stem cell transplant identified anaerobic isolates in 4% of bloodstream isolates, with a crude mortality of 11% [9]. Zahar et al. [6] examined anaerobic bacteremia in patients with cancer who received non-surgical treatment and showed a mortality rate of 14% if adequate antimicrobial therapy was received, compared with 63% for patients not treated with adequate antimicrobial cover. The IDSA clinical practice guidelines for the management of neutropenic fever recommend including anaerobic cover for patients who remain hemodynamically unstable after initial doses of