We evaluated targeted antimicrobial prophylaxis in men undergoing transrectal ultrasound guided prostate biopsy based on rectal swab culture results. From July 2010 to March 2011 we studied differences in infectious complications in men who received targeted vs standard empirical ciprofloxacin prophylaxis before transrectal ultrasound guided prostate biopsy. Targeted prophylaxis used rectal swab cultures plated on selective media containing ciprofloxacin to identify fluoroquinolone resistant bacteria. Patients with fluoroquinolone susceptible organisms received ciprofloxacin while those with fluoroquinolone resistant organisms received directed antimicrobial prophylaxis. We identified men with infectious complications within 30 days after transrectal ultrasound guided prostate biopsy using the electronic medical record. A total of 457 men underwent transrectal ultrasound guided prostate biopsy, and of these men 112 (24.5%) had rectal swab obtained while 345 (75.5%) did not. Among those who received targeted prophylaxis 22 (19.6%) men had fluoroquinolone resistant organisms. There were no infectious complications in the 112 men who received targeted antimicrobial prophylaxis, while there were 9 cases (including 1 of sepsis) among the 345 on empirical therapy (p=0.12). Fluoroquinolone resistant organisms caused 7 of these infections. The total cost of managing infectious complications in patients in the empirical group was $13,219. The calculated cost of targeted vs empirical prophylaxis per 100 men undergoing transrectal ultrasound guided prostate biopsy was $1,346 vs $5,598, respectively. Cost-effectiveness analysis revealed that targeted prophylaxis yielded a cost savings of $4,499 per post-transrectal ultrasound guided prostate biopsy infectious complication averted. Per estimation, 38 men would need to undergo rectal swab before transrectal ultrasound guided prostate biopsy to prevent 1 infectious complication. Targeted antimicrobial prophylaxis was associated with a notable decrease in the incidence of infectious complications after transrectal ultrasound guided prostate biopsy caused by fluoroquinolone resistant organisms as well as a decrease in the overall cost of care.

Zygomycosis is increasingly reported as a cause of life-threatening fungal infections. A higher proportion of cases reported over the last decades have been in cancer patients, with or without hematopoietic stem cell transplantation (HSCT). The new anti-fungal agent voriconazole is a recently identified risk factor for developing zygomycosis. We reviewed the clinical characteristics and outcomes of a large cohort of cancer patients who developed zygomycosis after exposure to voriconazole. Health care professionals at 13 large cancer centers provided clinical information on cancer patients with zygomycosis and prior exposure to voriconazole. Criteria for inclusion were 5 days or more of voriconazole use and diagnostic confirmation with tissue or histology. Fifty-eight cases were identified among patients with hematologic malignancies, 62% including patients who underwent a HSCT procedure. Fifty-six patients received voriconazole for primary or secondary prophylaxis against fungal infection. In addition to prior exposure to voriconazole, patients also had several of the previously established risk factors for zygomycosis. Amphotericin B was the most commonly prescribed anti-fungal therapy. Overall mortality was 73%. We conclude that zygomycosis after exposure to voriconazole is a recently described entity that is frequently fatal, despite treatment with currently available anti-fungal agents and surgery.

Background: This study analyzed the relationship between vancomycin area under the concentration-time curve (AUC) and acute kidney injury (AKI) reported across recent studies.Methods: A systematic review of PubMed, Medline, Scopus, and compiled references was conducted. We included randomized cohort and case-control studies that reported vancomycin AUCs and risk of AKI (from 1990 to 2018). The primary outcome was AKI, defined as an increase in serum creatinine of ≥0.5 mg/L or a 50% increase from baseline on ≥2 consecutive measurements. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Primary analyses compared the impact of AUC cutpoint (greater than ~650 mg × hour/L) and AKI. Additional analysis compared AUC vs trough-guided monitoring on AKI incidence.Results: Eight observational studies met inclusion/exclusion criteria with data for 2491 patients. Five studies reported first-24-hour AUCs (AUC0-24) and AKI, 2 studies reported 24- to 48-hour AUCs (AUC24-48) and AKI, and 2 studies reported AKI associated with AUC- vs trough-guided monitoring. AUC less than approximately 650 mg × hour/L was associated with decreased AKI for AUC0-24 (OR, 0.36 [95% CI, .23–.56]) as well as AUC24-48 (OR, 0.45 [95% CI, .27–.75]). AKI associated with the AUC monitoring strategy was significantly lower than trough-guided monitoring (OR, 0.68 [95% CI, .46–.99]).Conclusions: AUCs measured in the first or second 24 hours and lower than approximately 650 mg × hour/L may result in a decreased risk of AKI. Vancomycin AUC monitoring strategy may result in less vancomycin-associated AKI. Additional investigations are warranted.

Epidemiological studies have shown a link between carbapenem use and resistance; however, the clinical relationship between antibiotic consumption and the epidemiology of carbapenem-intermediate or -resistant Enterobacteriaceae (CIRE) remains unclear. This study sought to analyze temporal antibiotic consumption trends for relationships with incident CIRE. In total, 310,892 days of therapy and 55 deduplicated CIRE were analyzed. When conservative corrections were applied for multiple comparisons, carbapenem class use and piperacillin-tazobactam use retained significant positive and negative relationships with the incidence of CIRE, respectively.

Vancomycin is the most commonly administered antibiotic in hospitalized patients, but optimal exposure targets remain controversial. To clarify the therapeutic exposure range, this study evaluated the association between vancomycin exposure and outcomes in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. This was a prospective, multicenter (n = 14), observational study of 265 hospitalized adults with MRSA bacteremia treated with vancomycin. The primary outcome was treatment failure (TF), defined as 30-day mortality or persistent bacteremia ≥7 days. Secondary outcomes included acute kidney injury (AKI). The study was powered to compare TF between patients who achieved or did not achieve day 2 area under the curve to minimum inhibitory concentration (AUC/MIC) thresholds previously found to be associated with lower incidences of TF. The thresholds, analyzed separately as co-primary endpoints, were AUC/MIC by broth microdilution ≥650 and AUC/MIC by Etest ≥320. Treatment failure and AKI occurred in 18% and 26% of patients, respectively. Achievement of the prespecified day 2 AUC/MIC thresholds was not associated with less TF. Alternative day 2 AUC/MIC thresholds associated with lower TF risks were not identified. A relationship between the day 2 AUC and AKI was observed. Patients with day 2 AUC ≤515 experienced the best global outcomes (no TF and no AKI). Higher vancomycin exposures did not confer a lower TF risk but were associated with more AKI. The findings suggest that vancomycin dosing should be guided by the AUC and day 2 AUCs should be ≤515. As few patients had day 2 AUCs <400, further study is needed to define the lower bound of the therapeutic range.

Polymyxin B remains an antibiotic of last resort because of its toxicities. Although newer therapies are becoming available, it is anticipated that resistance to these agents will continue to emerge, and understanding the safest and most efficacious manner to deliver polymyxin B will remain highly important. Recent data have demonstrated that polymyxin B may be less nephrotoxic than colistin. Pharmacokinetically, polymyxin B is primarily eliminated via non-renal pathways, and most do not recommend adjusting the dose for renal impairment. However, some recent studies suggest a weak relationship between polymyxin B clearance and patient creatinine clearance. This review article will describe the clinical pharmacokinetics of polymyxin B and address relevant issues in chemistry and assays available.