Zapolskaya, T., Perreault, S., McManus, D., & Topal, J.E. (2018). Utility of fosfomycin as antibacterial prophylaxis in patients with hematologic malignancies. Supportive Care in Cancer, 26, 1979–1983.

To evaluate the incidence of breakthrough infections in patients with neutropenic hematologic malignancy unable to receive fluoroquinolone prophylaxis and receiving fosfomycin prophylaxis instead. Additional data collected to isolate offending organisms, types of infection, resistance patterns, and time from initiation of breakthrough infection to onset of fever.

• Intervention: For those patients with high-risk neutropenic hematologic malignancy unable to receive fluoroquinolone antibacterial prophylaxis: received fosfomycin 3 gm orally every 48 hours for neutropenic duration or until onset of first fever. Note: Fosfomycin was not held or discontinued due to any adverse effects
• Process: A retrospective chart review Yale-New Haven Hospital from December, 2011 to January, 2017, for patients with hematologic malignancies/HSCT receiving fosfomycin as antibacterial prophylaxis for neutropenia
• Inclusion criteria: Aged 18 years or older, documented history of fluoroquinolone-resistant organisms, allergies/intolerances of fluoroquinolones or other identified contraindications, minimum of three days fosfomycin 
• Exclusion criteria: Pediatric patients, use of fosfomycin for treatment of a culture-documented VRE UTI, unclear clinical indication and usage of fosfomycin and less than three days of treatment with fosfomycin 
• Procedure: The EMR was accessed to collect data for reason for admission, type of malignancy, type of HSCT, previous history of fluoroquinolone-resistant organism in last six months, history of VRE/MRSA documented by positive surveillance culture, time from initiation of fosfomycin to onset of fever spike (fever defined as temperature of 38.3°C occurring either as a single temperature at 38.3°C  or sustained temperature of 38.3°C  for greater than one hour), culture documented microbiology results of isolated organisms and clinical manifestations of infection collected. 
• Patients categorized as newly initiated fosfomycin prophylaxis as inpatient or a continuation from outpatient prophylaxis.

• N = 25 patients (data collected for these 25 patients across 42 admissions)  
• AGE: Median age = 56 years; range = 23-74 years
• MALES: 44%  
• FEMALES: 66%
• CURRENT TREATMENT: Chemotherapy, other
• KEY DISEASE CHARACTERISTICS: AML was most common, followed by MM, B-cell lymphoma, cutaneous T-cell lymphoma, ALL, CLL,  MCL, myeloproliferative neoplasm, and T-cell lymphoma 
• OTHER KEY SAMPLE CHARACTERISTICS: Reason for hospital admission: HSCT, chemotherapy, infection, NF, pneumonia, GVHD, N/V, and dizziness

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Yale-New Haven Connecticut

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Elder care

Retrospective chart review

Descriptive statistics of collected data: median, range, frequencies, incidence rates, and percentages

New start of fosfomycin prophylaxis = 81% of patients; continuation of fosfomycin prophylaxis = 19%; rate of FN while on fosfomycin prophylaxis = 55% (in 23 admissions), median time to start of fosfomycin to fever onset = 10.5 days (range = 3-21 days); breakthrough infections = 19% (in 42 admissions); bacterial organisms isolated: # 5 Klebsiella spp, # 2 S. mitis/viridans, #1 Pseudomonas aeruginosa, #1 coagulase-negative Staphylococcus; types of breakthrough infections: # 7 bacteremia, # 1 cellulitis, # 1 urine, # 1 bacteremia plus cellulitis; # 5 history of an infection six months prior to fosfomycin propylaxis, two of which had breakthrough infection not related to prior infection; no infection-related deaths for those experiencing breakthrough infections.

In a retrospective chart review of 25 neutropenic hematologic malignancy patients considered high risk for infection and unable to receive standard quinolones prophylaxis, received fosfomycin prophylaxis. The percentage of breakthrough infections while on fosfomycin prophylaxis was only 19%.

• Small sample (less than 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Findings not generalizable
• Other limitations/explanation: Retrospective study design unable to establish correlation or causality; limited statistical analysis

This retrospective chart review provides limited evidence for low rate of breakthrough infections on fosfomycin prophylaxis in high-risk hematologic malignancy patients. For those patients unable to receive fluoroquinolones, comparative effectiveness of fosfomycin as an alternative to fluoroquinolones needs further study with large multi-site RCTs.