Clinical Implications of Cefazolin Inoculum Effect and β-Lactamase Type on Methicillin-Susceptible<i>Staphylococcus aureus</i>Bacteremia

Lee, Shinwon; Kwon, Ki Tae; Kim, Hye In; Chang, Hyun Ha; Lee, Jong Myung; Choe, Pyoeng Gyun; Park, Wan Beom; Kim, Nam Joong; Oh, Myoung Don; Song, Dae Jin; Kim, Shin‐Woo

doi:10.1089/mdr.2013.0229

Cited by 48 publications

(64 citation statements)

References 30 publications

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“…Studies evaluating the clinical impact of the cefazolin inoculum effect are limited, and a relationship between these strains and adverse clinical outcomes has not been clearly established. A recent multicenter, retrospective cohort study examining the effects of MSSA isolates with and without the inoculum effect found no association between inoculum effect and overall treatment failure at 12 weeks in patients treated with cefazolin for MSSA bacteremia (24). However, the inoculum effect was associated with early treatment failure (OR, 4.89; 95% CI, 1.00 to 22.23; P ϭ 0.04).…”

Section: Discussionmentioning

confidence: 97%

Comparison of Cefazolin versus Oxacillin for Treatment of Complicated Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus

Echevarria

Hughes

et al. 2014

Antimicrob Agents Chemother

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e Contrary to prior case reports that described occasional clinical failures with cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infections, recent studies have demonstrated no difference in outcomes between cefazolin and antistaphylococcal penicillins for the treatment of MSSA bacteremia. While promising, these studies described low frequencies of high-inoculum infections, such as endocarditis. This retrospective study compares clinical outcomes of cefazolin versus oxacillin for complicated MSSA bacteremia at two tertiary care hospitals between January 2008 and June 2012. Fifty-nine patients treated with cefazolin and 34 patients treated with oxacillin were included. Osteoarticular (41%) and endovascular (20%) sources were the predominant sites of infection. The rates of clinical cure at the end of therapy were similar between cefazolin and oxacillin (95% versus 88%; P ‫؍‬ 0.25), but overall failure at 90 days was higher in the oxacillin arm (47% versus 24%; P ‫؍‬ 0.04). Failures were more likely to have received surgical interventions (63% versus 40%; P ‫؍‬ 0.05) and to have an osteoarticular source (57% versus 33%; P ‫؍‬ 0.04). Failures also had a longer duration of bacteremia (7 versus 3 days; P ‫؍‬ 0.0002), which was the only predictor of failure. Antibiotic selection was not predictive of failure. Rates of adverse drug events were higher in the oxacillin arm (30% versus 3%; P ‫؍‬ 0.0006), and oxacillin was more frequently discontinued due to adverse drug events (21% versus 3%; P ‫؍‬ 0.01). Cefazolin appears similar to oxacillin for the treatment of complicated MSSA bacteremia but with significantly improved safety. The higher rates of failure with oxacillin may have been confounded by other patient factors and warrant further investigation.

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Section: Discussionmentioning

confidence: 97%

Comparison of Cefazolin versus Oxacillin for Treatment of Complicated Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus

Echevarria

Hughes

et al. 2014

Antimicrob Agents Chemother

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“…However, it is not uncommon to find MSSA isolates with the type A blaZ gene that do not show a CIE (3,11,12). Although some experts suggest that variation of the CIE among MSSA isolates with the type A blaZ gene is the result of differences in the amount of ␤-lactamase produced, the exact cause of this variation remains unclear.…”

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confidence: 99%

“…However, there are concerns about cefazolin therapeutic failures and relapses in the treatment of MSSA strains that demonstrate the CIE (2,3,20,21). Previous studies have demonstrated that the CIE in MSSA is closely associated with the blaZ type, and type A blaZ-positive MSSA can present a CIE (3,11,12,22,23). However, the prevalence of CIE positivity among MSSA strains positive for type A blaZ is variable, and approximately 15 to 65% of these strains exhibited no CIE (3,11,12,22,23).…”

mentioning

confidence: 99%

“…Previous studies have demonstrated that the CIE in MSSA is closely associated with the blaZ type, and type A blaZ-positive MSSA can present a CIE (3,11,12,22,23). However, the prevalence of CIE positivity among MSSA strains positive for type A blaZ is variable, and approximately 15 to 65% of these strains exhibited no CIE (3,11,12,22,23). Livorsi et al (12) reported that only 17% of type A blaZ-positive MSSA isolates exhibited a CIE, whereas Lee et al (11) reported that 65% did so.…”

mentioning

confidence: 99%

“…However, the prevalence of CIE positivity among MSSA strains positive for type A blaZ is variable, and approximately 15 to 65% of these strains exhibited no CIE (3,11,12,22,23). Livorsi et al (12) reported that only 17% of type A blaZ-positive MSSA isolates exhibited a CIE, whereas Lee et al (11) reported that 65% did so.…”

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confidence: 99%

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Association between Type A blaZ Gene Polymorphism and Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus

Lee

Park

Lee

et al. 2016

Antimicrob Agents Chemother

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Evaluation of Meropenem‐Ciprofloxacin Combination Dosage Regimens for the Pharmacokinetics of Critically Ill Patients With Augmented Renal Clearance

Agyeman

Rogers

Tait

et al. 2021

Clin Pharma and Therapeutics

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Augmented renal clearance (ARC, creatinine clearance > 130 mL/minute) makes difficult achievement of effective concentrations of renally cleared antibiotics in critically ill patients. This study examined the synergistic killing and resistance suppression for meropenem-ciprofloxacin combination dosage regimens against Pseudomonas aeruginosa isolates within the context of ARC. Clinically relevant meropenem and ciprofloxacin concentrations, alone and in combinations, were studied against three clinical isolates with a range of susceptibilities to each of the antibiotics. Isolate Pa1280 was susceptible to both meropenem and ciprofloxacin, Pa1284 had intermediate susceptibility to meropenem and was susceptible to ciprofloxacin, and CR380 was resistant to meropenem and had intermediate susceptibility to ciprofloxacin. Initially, isolates were studied in 72-hour static-concentration time-kill (SCTK) studies. Subsequently, the pharmacokinetic profiles expected in patients with ARC receiving dosage regimens, including at the highest approved daily doses (meropenem 6 g daily divided and administered as 0.5-hour infusions every 8 hours, or as a continuous infusion; ciprofloxacin 0.4 g as 1-hour infusions every 8 hours), were examined in a dynamic hollow-fiber infection model (HFIM) over 7-10 days. In both SCTK and HFIM, combination regimens were generally synergistic and suppressed growth of less-susceptible subpopulations, these effects being smaller for isolate CR380. The time-courses of total and less-susceptible bacterial populations in the HFIM were well-described by mechanismbased models, which enabled conduct of Monte Carlo simulations to predict likely effectiveness of approved dosage regimens at different creatinine clearances. Optimized meropenem-ciprofloxacin combination dosage regimens may be a viable consideration for P. aeruginosa infections in critically ill patients with ARC.

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Clinical Implications of Cefazolin Inoculum Effect and β-Lactamase Type on Methicillin-SusceptibleStaphylococcus aureusBacteremia

Abstract: The CIE might be associated with persistent bacteremia if cefazolin is used for MSSA bacteremia with a high burden of infections. However, the sites of infections are more important factors for the clinical outcome than the CIE.

Cited by 48 publications

References 30 publications

Comparison of Cefazolin versus Oxacillin for Treatment of Complicated Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus

Comparison of Cefazolin versus Oxacillin for Treatment of Complicated Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus

Association between Type A blaZ Gene Polymorphism and Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus

Evaluation of Meropenem‐Ciprofloxacin Combination Dosage Regimens for the Pharmacokinetics of Critically Ill Patients With Augmented Renal Clearance

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