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Cefazolin Inoculum Effect and Methicillin-Susceptible Staphylococcus aureus Osteoarticular Infections in Children.

ABSTRACT: Select methicillin-susceptible Staphylococcus aureus (MSSA) strains may produce ?-lactamases with affinity for first-generation cephalosporins (1GCs). In the setting of a high inoculum, these ?-lactamases may promote the cleavage of 1GCs, a phenomenon known as the cefazolin inoculum effect (CzIE). We evaluated the prevalence and impact of CzIE on clinical outcomes among MSSA acute hematogenous osteomyelitis (AHO) cases. MSSA AHO isolates obtained from two children's hospitals between January 2011 and December 2018 were procured through ongoing surveillance studies. Isolates were tested for CzIE via a broth macrodilution assay using an inoculum of 10⁷ CFU/ml; CzIE was defined as a cefazolin MIC?of ?16??g/ml. Isolates were characterized by accessory gene regulator group (agr). The progression from acute to chronic osteomyelitis was considered an important outcome. A total of 250 cases with viable isolates were included. Notably, 14.4% of isolates exhibited CzIE with no observed temporal trend; and 4% and 76% of patients received a 1GC as an empirical and definitive therapy, respectively. CzIE isolates were more often resistant to clindamycin, belonged to agrIII, and associated with the development of chronic osteomyelitis. In multivariable analyses, agrIII, multiple surgical debridements, delayed source control, and CzIE were independently associated with progression to chronic osteomyelitis. A higher rate of chronic osteomyelitis was observed with CzIE isolates regardless of definitive antibiotic choice. CzIE is exhibited by 14.4% of MSSA AHO isolates in children. CzIE is independently associated with progression to chronic osteomyelitis in cases of AHO irrespective of final antibiotic choice. These data suggest that negative outcomes reported with CzIE may more accurately reflect strain-dependent virulence factors rather than true antibiotic failure.

SUBMITTER: McNeil JC

PROVIDER: S-EPMC7449214 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Cefazolin Inoculum Effect and Methicillin-Susceptible Staphylococcus aureus Osteoarticular Infections in Children.

McNeil J Chase JC Sommer Lauren M LM Boyle Mary M Hogan Patrick P Vallejo Jesus G JG Hultén Kristina G KG Flores Anthony R AR Kaplan Sheldon L SL Fritz Stephanie S

Antimicrobial agents and chemotherapy 20200820 9

Select methicillin-susceptible <i>Staphylococcus aureus</i> (MSSA) strains may produce β-lactamases with affinity for first-generation cephalosporins (1GCs). In the setting of a high inoculum, these β-lactamases may promote the cleavage of 1GCs, a phenomenon known as the cefazolin inoculum effect (CzIE). We evaluated the prevalence and impact of CzIE on clinical outcomes among MSSA acute hematogenous osteomyelitis (AHO) cases. MSSA AHO isolates obtained from two children's hospitals between Janu ...[more]

PMID: 32660989

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Project description:BackgroundBloodstream infections due to Staphylococcus aureus cause significant patient morbidity and mortality worldwide. Of major concern is the emergence and spread of methicillin-resistant S. aureus (MRSA) in bloodstream infections, which are associated with therapeutic failure and increased mortality.MethodsWe generated high quality draft genomes from 323 S. aureus blood culture isolates from patients diagnosed with bloodstream infection at the Dartmouth-Hitchcock Medical Center, New Hampshire, USA in 2010-2018.ResultsIn silico detection of antimicrobial resistance genes revealed that 133/323 isolates (41.18%) carry horizontally acquired genes conferring resistance to at least three antimicrobial classes, with resistance determinants for aminoglycosides, beta-lactams and macrolides being the most prevalent. The most common resistance genes were blaZ and mecA, which were found in 262/323 (81.11%) and 104/323 (32.20%) isolates, respectively. Majority of the MRSA (102/105 isolates or 97.14%) identified using in vitro screening were related to two clonal complexes (CC) 5 and 8. The two CCs emerged in the New Hampshire population at separate times. We estimated that the time to the most recent common ancestor of CC5 was 1973 (95% highest posterior density (HPD) intervals: 1966-1979) and 1946 for CC8 (95% HPD intervals: 1924-1959). The effective population size of CC8 increased until the late 1960s when it started to level off until late 2000s. The levelling off of CC8 in 1968 coincided with the acquisition of SCCmec Type IV in majority of the strains. The plateau in CC8 also coincided with the acceleration in the population growth of CC5 carrying SCCmec Type II in the early 1970s, which eventually leveled off in the early 1990s. Lastly, we found evidence for frequent recombination in the two clones during their recent clonal expansion, which has likely contributed to their success in the population.ConclusionsWe conclude that the S. aureus population was shaped mainly by the clonal expansion, recombination and co-dominance of two major MRSA clones in the last five decades in New Hampshire, USA. These results have important implications on the development of effective and robust strategies for intervention, control and treatment of life-threatening bloodstream infections.

Project description:Prior studies of pediatric musculoskeletal infection have suggested that methicillin-resistant Staphylococcus aureus (MRSA) infections result in worse outcomes compared with infections with methicillin-susceptible S aureus (MSSA) strains. Based on these results, clinical prediction algorithms have been developed to differentiate between MRSA and MSSA early in a patient's clinical course. This study compares hospital outcomes for pediatric patients with MRSA and MSSA musculoskeletal infection presenting to the emergency department at a large tertiary care children's hospital.A retrospective study identified pediatric patients with S aureus musculoskeletal infection over a 5-year period (2008-2013) by sequential review of all pediatric orthopedic consults. Relevant demographic information, laboratory values, and clinical outcomes were obtained from the electronic medical record.Of the 91 identified cases of S aureus pediatric musculoskeletal infection, there were 49 cases of MRSA infection (53%) and 42 cases of MSSA infection (47%). There were no significant differences between MRSA and MSSA infections in median hospital length of stay (4.8 vs 5.7 days, P = .50), febrile days (0.0 vs 1.5 days, P = .10), and antibiotic duration (28 vs 34 days, P = .18). Methicillin-resistant S aureus infections were more likely to require operative intervention than MSSA infection (85% vs 62%, P = .15). A logistic regression model based on C-reactive protein, temperature, white blood cell count, pulse, and respiratory rate at presentation demonstrated poor ability to differentiate between MRSA and MSSA infection.The results demonstrated no significant differences between MSSA and MRSA musculoskeletal infections for most hospital outcomes measured. However, MRSA infections required more operative interventions than MSSA infections. In addition, a predictive model based on severity markers obtained at presentation was unable to effectively differentiate between MRSA and MSSA infection. The clinical utility and capacity for early differentiation of MRSA and MSSA depends on virulence patterns that may vary temporally and geographically.

Dataset Information

Cefazolin Inoculum Effect and Methicillin-Susceptible Staphylococcus aureus Osteoarticular Infections in Children.

Publications

Cefazolin Inoculum Effect and Methicillin-Susceptible Staphylococcus aureus Osteoarticular Infections in Children.

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