Study objective To evaluate the observed incidence of acute kidney injury (AKI) in adult patients receiving either piperacillin-tazobactam and vancomycin or cefepime-vancomycin for more than 48 hours. Design Retrospective matched cohort. Setting Large academic medical center. Patients Adult patients without preexisting renal dysfunction admitted over an 8-month time period who received either the combination of piperacillin-tazobactam and vancomycin or cefepime-vancomycin for more than 48 hours were evaluated for AKI, defined by the Acute Kidney Injury Network criteria. Measurements and main results A total of 224 patients receiving either antimicrobial combination were evaluated for AKI. The incidence of AKI was significantly higher in the piperacillin-tazobactam and vancomycin group (34.8%) compared with the cefepime-vancomycin group (12.5%) in the unmatched analysis (p Conclusions The results of this study suggest that there may be an association between piperacillin-tazobactam and vancomycin combination therapy and increased incidence of AKI.

Comparison of acute kidney injury during treatment with vancomycin in combination with piperacillin-tazobactam or cefepime

β-lactam antibiotics: An overview from a medicinal chemistry perspective.

Penicillin allergy is often diagnosed early in life, and the history of penicillin allergy persists in a patient’s medical record for many years without verification. Some physicians’ consideration of a patient having penicillin allergy is based on patient experience that may have occurred early in childhood. This results in the use of alternate antibiotics that are less effective, more toxic and expensive, and that have inappropriately broader coverage than penicillin.1 Accumulating evidence suggests that excessive use of unnecessarily broad-spectrum antibiotics increases the risk of antibiotic resistance, including Clostridium difficile infection.2 The inability to use an antistaphylococcal penicillin (eg, nafcillin) for patients with methicillin-susceptible Staphylococcus aureus sepsis or other serious infections for which penicillins are the first-line therapy (eg, ampicillin for Enterococcus faecalis or benzathine penicillin for syphilis) places patients at risk of treatment failure, resistance generation, and increased mortality.

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Penicillin Allergy Is Not Necessarily Forever

Penicillin and Cephalosporin allergy

In total joint arthroplasty (TJA), vancomycin is used as perioperative antibiotic prophylaxis in patients with penicillin allergy or in patients colonized with methicillin-resistant Staphylococcus aureus (MRSA). Although vancomycin dosing should be weight-based (15 mg/kg), not all surgeons are aware of this; a fixed 1-g dose is instead frequently administered. (1) Is there a difference in the risk of periprosthetic joint infection (PJI) in patients receiving vancomycin or cefazolin prophylaxis after primary TJA? (2) What proportion of patients is adequately dosed with vancomycin? (3) Compared with actual fixed dosing, does weight-based dosing result in a greater proportion of patients staying above the recommended 15-mg/L level at the beginning and end of surgery? (4) Are patients overdosed with vancomycin at greater risk of developing nephrotoxicity and acute kidney injury? A single-institution, retrospective study was performed on 1828 patients undergoing primary TJAs who received vancomycin prophylaxis between 2008 and 2014. During the same period, 5810 patients underwent primary TJA and received cefazolin monotherapy. A chart review was performed to obtain patient characteristics, antibiotic dose and timing of administration, and microbiology data. Adequate vancomycin dosing was defined as 15 mg/kg and within the 125-mg range. Vancomycin levels were calculated at the beginning and end of surgery using pharmacokinetic equations. Levels of 15 mg/L were considered adequate. Logistic regression, chi square tests, and analysis of variance were performed. Among primary TJAs, patients receiving vancomycin had a higher rate of PJI (32 of 1828 [2%]) compared with patients receiving cefazolin prophylaxis (62 of 5810 [1%]; adjusted odds ratio, 1.587 [1.004–2.508]; p = 0.048). Ten percent of PJIs in the vancomycin underdosed group (two of 20) was caused by MRSA, and no patients with adequate dosing or overdosing of vancomycin developed PJI with MRSA. Of all procedures in which vancomycin monotherapy was used, 28% (518 of 1828) was adequately dosed according to weight-based dosage recommendations. Furthermore, 94% (1726 of 1828) of patients received a fixed 1-g dose of vancomycin, of whom 64% (1105 of 1726) were underdosed. All patients had vancomycin infusion initiated within 2 hours before incision. A weight-based protocol would have resulted in fewer patients having unacceptably low vancomycin levels (< 15 mg/L) compared with those with actual fixed dosing, both for the beginning of surgery at the time of incision (zero of 1828 [0%] versus 471 of 1828 [26%]; odds ratio, 0.001 [0.000–0.013]; p < 0.001) and at the end of surgery (33 of 1828 [2%] versus 746 of 1828 [41%]; odds ratio, 0.027 [0.019–0.038]; p < 0.001). Between the vancomycin dosage groups, there were no differences in the rate of nephrotoxicity (underdosed: 12 of 1130 [1%], adequately dosed: five of 518 [1%], overdosed: four of 180 [2%], p = 0.363) and acute kidney injury (underdosed: 28 of 1130 [2%], adequately dosed: 10 of 518 [2%], overdosed: six of 180 [3%], p = 0.561). The majority of patients given vancomycin prophylaxis are underdosed according to the weight-based dosage recommendations, and MRSA did not occur in patients who were adequately dosed with vancomycin. Surgeons should thus ensure that their patients are adequately dosed with vancomycin using the recommendation of 15 mg/kg and that the dose of vancomycin is administered in a timely fashion. Furthermore, and based on the findings of this study, we have moved toward limiting the utilization of vancomycin prophylaxis for patients undergoing elective arthroplasty at our institution. Level III, therapeutic study.

/pdf/vancomycin-prophylaxis-for-total-joint-arthroplasty-203dnnhv55.pdf

Vancomycin Prophylaxis for Total Joint Arthroplasty: Incorrectly Dosed and Has a Higher Rate of Periprosthetic Infection Than Cefazolin.

Background The practice of avoiding cephalosporin administration to penicillin-allergic patients persists despite the low rate of cross reactions between both groups of antibiotics. Objective The purpose of this literature review is to evaluate the published evidence regarding the commonly held belief that patients with a history of an allergic reaction to penicillin have a significantly increased risk of an allergic reaction to cephalosporins. Materials and Methods Articles were identified through a computerized search of MEDLINE from 1950 to the present using the search terms “penicillin$,” “cephalosporin$,” “allerg$,” “hypersensitivity,” and “cross-react$.” All articles were reviewed, and additional sources cited in them were added to the literature review. Results Penicillins have a cross allergy with first-generation cephalosporins (odds ratio 4.8; confidence interval 3.7–6.2) and a negligible cross allergy with second-generation cephalosporins (odds ratio 1.1; confidence interval 0.6–2.1). Laboratory and cohort studies confirm that the R1 side chain is responsible for this cross reactivity. Overall cross reactivity between penicillins and cephalosporins is lower than previously reported, though there is a strong association between amoxicillin and ampicillin with first- and second-generation cephalosporins that share a similar R1 side chain. Conclusions Although a myth persists that approximately 10% of patients with a history of penicillin allergy will have an allergic reaction if given a cephalosporin, the overall cross-reactivity rate is approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains. However, a single study reported the prevalence of cross reactivity with cefadroxil as high as 27%. For penicillin-allergic patients, the use of third- or fourth-generation cephalosporins or cephalosporins with dissimilar side chains than the offending penicillin carries a negligible risk of cross allergy.

Esteban Schabelman

Papers

The Use of Cephalosporins in Penicillin-allergic Patients: A Literature Review