MDRO Infections in Patients with Neutropenic Fever

Patients with cancer who are receiving chemotherapy and subsequently develop neutropenia commonly experience fevers, especially those with hematological malignancies (more than 80%) compared with those with solid cancers (10% to 15%).¹

Definitions vary between guidelines and institutions, however a common definition of neutropenia is an absolute neutrophil count (ANC) less than 1,500 cells/µL with severe or profound neutropenia defined as ANC less than 500 cells/µL.¹

It is often difficult to discern whether or not neutropenic fevers are infectious in etiology, as many of these patients are inherently immunosuppressed and may not manifest the typical clinical symptoms associated with an infection. During a hospital stay, blood cultures are frequently drawn when the neutropenic patient has a documented fever 100.4ºF or higher.

However, less than 25% of these patients will actually be bacteremic and less than 30% will have a documented infectious source.¹ The most common sources of infection include the lung, skin, urinary tract, and gastrointestinal tract.

When bacterial sources are isolated, both gram positive and gram negative organisms have been identified. Gram positive isolates are typically more common and include Streptococcus, Enterococcus, Staphylococcus aureus, and coagulase-negative staph.

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Gram negative bacteria are less common but the most lethal and include Pseudomonas, Klebsiella, E coli, Acinetobacter, and Enterobacter. As the over-utilization of antiobiotics has become relatively common (both as inpatients and outpatients), many of these bacteria have developed resistance mechanisms rendering many antibiotics ineffective.²

There are variations in the definition of what exactly a multidrug resistant organism (MDRO) is, however the Centers for Disease Control and Prevention defines MDROs as “microorganisms, predominantly bacteria, that are resistant to one or more classes of antimicrobial agents.”³ 

Examples of MDROs include methicillin-resistant staph aureus (MRSA), vancomycin-resistant enterococcus, extended spectrum beta-lactamase (ESBL)-producing Klebsiella and E coli, and carbapenemase-producing organisms such as Klebsiella pneumoniae carbapenemase (KPC).

When evaluating a patient with neutropenic fever for a possible MDRO infection, several factors should be considered. A thorough physical exam should be completed and common sources of infection should be ruled out. All foreign objects including central venous catheters, IV lines, peripherally inserted central catheters (PICC), urinary catheters and feeding tubes should be closely inspected and removed as soon as clinically possible. 

Within a hospital or community, it is important to review the most common pathogens along with the corresponding antibiogram. A patient’s prior antiobiotic use and cultures should be reviewed in order to search for the development of any potential resistance patterns.

Protective gowns and gloves can be utilized if there is a possibility of coming in contact with MDROs. In addition, proper hand-washing techniques can be used instead of alcohol-based antiseptics.

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As many patients with neutropenic fever will not have positive blood cultures, the choice of antibiotics to combat potential MDROs can be challenging. In general, the following antibiotics should be considered when a specific MDRO is suspected: MRSA (vancomycin, linezolid, daptomycin), VRE (linezolid, daptomycin), ESBLs (carbapenems), Carbapenemase-producing organisms (tigecycline, polymyxin-colistin).¹

This list is not exhaustive nor does it address the most appropriate antibiotic for the type of infection suspected, therefore the antibiotic choice must be tailored to the patient’s clinical scenario.

References

1. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011;52(4):e56-e93.
2. Oliveira AL, de Souza M, Carvalho-Dias VM, et al. Epidemiology of bacteremia and factors associated with multi-drug-resistant gram-negative bacteremia in hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2007;39:775-781.
3. Siegel JD, Rhinehart E, Jackson M, et al. Management of Multidrug-Resistant Organisms in Healthcare Settings, 2006. Am J Infect Control. 2007;35(10 Suppl 2):S165-S193.