Are You Going Overboard on Cephalosporins?

The study

This prospective chart review study (2011–2013) from Texas included infants aged ≤60 days with a positive culture from the blood, urine, or cerebrospinal fluid. The researcher’s objectives were to study the pathogens and the optimal choice of antibiotics in infants with serious bacterial infection (SBI).

The key findings

The study found 265 infants with SBI. Of those infants, 11% had meningitis, 25% had bacteremia or bacteremia with urinary tract infection, and 64% had urinary tract infection alone. Escherichia coli and group B Streptococcus were the predominate pathogens. There were no cases of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, or penicillin-resistant Streptococcus pneumonia. For infants aged ≤28 days, the combination of ampicillin and gentamicin was used in 78% of cases, whereas a third-generation cephalosporin was used in 22% of cases. For infants aged ≥29 days, ampicillin and gentamicin were used in 13% of cases, and a third-generation cephalosporin was used in 87% of cases.

The authors noted that when meningitis was not suspected, regimens of either ampicillin/gentamicin or a third-generation cephalosporin were equally effective based on susceptibility data (96% and 97%). They also noted that 67% of cases in which a third-generation cephalosporin was used resulted in unnecessarily broad coverage compared with ampicillin/gentamicin. Also, 57% of third-generation courses were continued despite susceptibility results allowing deescalation of therapy.

Why do we care?

Hospitalized infants with fever and suspected SBI are our wheelhouse. We love third-generation cephalosporins, especially for infants aged 29 days and older. This study suggests that for infants in whom meningitis is not suspected, we should be using gentamicin instead of a cephalosporin to avoid antibiotic resistance. Our love for cephalosporins may also be preventing us from narrowing our coverage once susceptibilities are known.

The study

This retrospective chart review looked to identify risk factors for acute kidney injury (AKI) in patients aged 3 months to 18 years treated with intravenous vancomycin while admitted to a tertiary care center between February 2009 and September 2010. AKI was defined as having a 50% decrease in estimated GFR during or up to 72 hours after vancomycin therapy. Patients were excluded if they received vancomycin for <48 hours, received vasopressors 48 hours before to 72 hours after vancomycin therapy, had a transplanted or solitary kidney, had tumor lysis syndrome, or lacked baseline laboratory data. Vancomycin dosing was studied rather than measured serum levels such that AKI independent of vancomycin causing an elevation in levels would not confound the results.

The key findings

Of the 175 patients included, 24 (13.7%) met AKI criteria. Odds of AKI markedly increased with coadministration of nephrotoxic medications (odds ratio [OR] = 5.02; 95% confidence interval [CI] = 1.09–23.19). Patients with AKI received a median of 1 (interquartile range = 0–2) nephrotoxic medication concurrently with vancomycin, whereas patients without AKI received a median of 0 concurrent nephrotoxic medications (interquartile range = 0–1; P = .042).

A multivariate regression showed that the likelihood of AKI increased with each 5-mg/kg increase in vancomycin dose (OR = 1.16; 95% CI = 1.01–1.33) and with each additional day of therapy (OR = 1.11; 95% CI = 1.01–1.22). In all models, concurrent use of nephrotoxic medications and longer durations of therapy were associated with increased odds of AKI.

Why do we care?

With higher vancomycin dosing for many infections after 2009 Infectious Diseases Society of America recommendations¹ and evidence mounting that even transient AKI in childhood is associated with deleterious effects later in life,² it is more important than ever to give forethought to prevention of AKI in children receiving vancomycin. As hospitalists, we should be at the center of quality improvement initiatives using systems of care to prevent harm. Potential avenues for improvement include prompts to discontinue antibiotics as soon as medically reasonable, changes to less toxic antibiotics, and avoidance of other nephrotoxic medications while prescribing vancomycin.