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Monitoring for antibiotic-related lab abnormalities (ARLA), including hematologic, renal, and/or hepatic toxicity, in pediatric osteomyelitis is common. In 240 cases of osteomyelitis with outpatient laboratory monitoring, ARLA occurred in 13.3% with the most common finding being neutropenia. ARLA impacted antibiotic therapy in <1% of subjects, however, raising questions about the value of such monitoring being performed routinely., Competing Interests: J.C.M. receives support through AHRQ R01HS026896 and Merck for unrelated work. He is also a site investigator on a clinical trial sponsored by Nabriva also unrelated to the work under consideration. S.L.K. receives grant funding from Pfizer for unrelated research. All other authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Shortly after its introduction into clinical practice, Staphylococcus aureus isolates gained resistance to penicillin via the acquisition of β-lactamases. A number of centers have recently described an increase in the proportion of invasive methicillin-susceptible S. aureus (MSSA), which are also susceptible to penicillin (PSSA). Little data are available regarding the prevalence or impact of PSSA in skin and soft tissue infections (SSTI). Community-acquired MSSA SSTI isolates were obtained through a surveillance study at Texas Children's Hospital from January 2017 to December 2021. A total of 200 random isolates underwent PCR for blaZ β-lactamase; blaZ -negative isolates then underwent penicillin susceptibility testing using macrobroth dilution. Isolates which were blaZ negative and had a penicillin MIC ≤0.125 µg/mL were regarded as PSSA with the remainder regarded as penicillin-resistant MSSA (PR-MSSA). All PSSA underwent multilocus sequence typing. Medical records were reviewed. The median age of subjects was 4.2 years (IQR: 1.6-10.5). PSSA accounted for 9% of isolates during the study period. PSSA and PR-MSSA cases were similar with respect to age, demographics, and rates of prior antibiotic exposure. PSSA isolates less often had vancomycin MIC ≥1.5 µg/mL. Furthermore, 39% of PSSA were variants of sequence type 1. In multivariable analyses, penicillin susceptibility was independently associated with both hospital admission and surgical intervention. PSSA account for a small but significant proportion of MSSA SSTI in children. Clinically distinguishing patients with PSSA and PR-MSSA SSTI is challenging. However, PSSA SSTI were independently associated with higher rates of hospital admission as well as the need for surgical intervention suggesting a significant clinical impact.IMPORTANCEThe vast majority of Staphylococcus aureus in the US are penicillin resistant with most clinical labs no longer reporting penicillin susceptibility for this organism. A number of centers, however, have reported increasing penicillin susceptibility among invasive S. aureus infections. Skin and soft tissue infections (SSTI) are far more common than invasive infections, yet the frequency and impact of penicillin-susceptible S. aureus (PSSA) in this population are uncertain. Through active surveillance at a children's hospital, we found that 9% of methicillin-susceptible S. aureus SSTI isolates were PSSA. PSSA were independently associated with hospital admission for the management of SSTI as well as the need for debridement in the operating room. Given that most SSTI are managed in the outpatient setting, these findings suggest a clinical impact of this phenotype and the need for a reassessment of the value in susceptibility testing and potentially even treatment with penicillin., Competing Interests: J.C.M. receives grant support through Merck for unrelated research and is a site investigator on a clinical trial sponsored by Nabriva (also unrelated to the work under consideration). S.L.K. and K.G.H. receive support through Pfizer for unrelated work.

We investigated the microbiology, management, and orthopedic outcomes of osteoarticular infections in infants age ≤1 year at our institution. Among 87 patients, Staphylococcus aureus was the most common pathogen (44.8%), followed by group B Streptococcus. Twenty-nine patients (33%), with a median age of 9.2 months, were transitioned to oral antibiotic therapy after ≤14 days of parenteral therapy; orthopedic outcomes were similar to those with prolonged parenteral therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Staphylococcus aureus is a common pathogen seen in pediatric bloodstream infections. Currently, no evidence-based recommendations are used to guide decisions on the number of follow-up blood cultures (FUBCs) needed to demonstrate infection clearance. Unnecessary cultures increase the risk of false-positives, add to health care costs, and create additional trauma to children and their families. In this study, we examined risk factors for persistent S aureus bacteremia (SAB) and intermittent positive blood cultures (positive cultures obtained after a documented negative FUBC result) to determine the number of FUBCs needed to demonstrate infection clearance in children., Methods: Patients ≤18 years who were hospitalized with SAB at Texas Children's Hospital in 2018 were reviewed. We assessed the impact of an infectious disease diagnosis (central line-associated bloodstream infection, osteomyelitis, soft tissue infection, endocarditis, etc) and medical comorbidities on bacteremia duration. Patients with intermittent positive blood cultures were studied to determine the characteristics of this group and overall frequency of reversion to positive cultures., Results: A total of 122 subjects met the inclusion criteria. The median duration of bacteremia was 1 day (interquartile range: 1-2 days). Only 19 patients (16%) had bacteremia lasting ≥3 days, all of whom had a diagnosis of central line-associated bloodstream infection, osteomyelitis, or endocarditis. Intermittent positive cultures occurred in 5% of patients, with positive cultures after 2 negative FUBC results seen in <1% of patients. Intermittent positive cultures were strongly associated with osteomyelitis and endocarditis., Conclusions: On the basis of our sample of children with SAB, additional blood cultures to document sterility are not necessary after 2 FUBC results are negative in well-appearing patients., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Staphylococcus aureus is a common cause of community and health care-associated bacteremia, with authors of recent studies estimating the incidence of S aureus bacteremia (SAB) in high-income countries between 8 and 26 per 100 000 children per year. Despite this, <300 children worldwide have ever been randomly assigned into clinical trials to assess the efficacy of treatment of SAB. A panel of infectious diseases physicians with clinical and research interests in pediatric SAB identified 7 key clinical questions. The available literature is systematically appraised, summarizing SAB management in children in relation to these priority clinical questions. The management of neonates, children, and adolescents with SAB is predominantly based on clinical experience and trial data extrapolated from adult studies, with limited high-quality evidence available to guide management. The optimal, comprehensive management strategies for SAB in children will remain unknown until the questions outlined are answered through prospective observational cohorts and inclusion of children with SAB in clinical trials., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Background: Bacteremia is often one factor used in deciding the need for prolonged intravenous antimicrobial therapy in osteoarticular infections (OAIs). We examined treatment practices and outcomes of Staphylococcus aureus bacteremic osteoarticular infections (BOAIs) evaluated at Texas Children's Hospital., Methods: Cases of acute hematogenous OAI in children with positive blood cultures for S. aureus at Texas Children's Hospital between 2011 and 2014 were reviewed. Orthopedic complications included chronic osteomyelitis, growth arrest, pathologic fracture, avascular necrosis and chronic dislocation. Acute kidney injury was defined as a doubling of the baseline creatinine., Results: One hundred and ninety-two cases of S. aureus OAI were identified with 102 cases of BOAI included [35 methicillin-resistant S. aureus (MRSA)]. Twenty-five patients were discharged home on oral antibiotics. Patients discharged on oral antibiotics had a shorter duration of fever, had a more rapid decline in C-reactive protein and were less likely to have MRSA. The frequency of orthopedic complications did not increase in patients who received early transition to oral antibiotics. For patients with MRSA bacteremia, the rates of complications between those who received ≥7 days versus <7 days of vancomycin did not differ. Vancomycin serum troughs >15 µg/mL were not associated with a decreased duration of fever, bacteremia or hospitalization, need for repeat operation or orthopedic complications but were associated with acute kidney injury., Conclusions: S. aureus BOAIs are associated with substantial morbidity. Early transition to oral therapy may be a safe option for select patients with S. aureus BOAI, including those due to MRSA. Prolonged courses of vancomycin and vancomycin troughs >15 μg/mL were not associated with improved outcomes for MRSA OAI.

Piperacillin-tazobactam is used frequently in pediatric patients with complicated appendicitis and other intra-abdominal infections. We report 10 pediatric patients who developed a piperacillin-tazobactam-associated adverse reaction characterized by fever, rash, hematologic abnormalities and transaminitis. Physicians should be aware of this entity in patients treated with a prolonged course of piperacillin-tazobactam. Prompt identification can obviate unnecessary diagnostic testing and treatment.

Topical antimicrobial and antiseptic agents are commonly used in the management of minor skin and soft tissue infections (SSTIs). Resistance to mupirocin has been documented in Staphylococcus aureus isolates causing SSTIs. Data are limited, however, on the prevalence of retapamulin resistance or tolerance to antiseptics. We sought to determine the prevalence of decreased susceptibility to retapamulin and mupirocin as well as the potential for decreased chlorhexidine susceptibility of S. aureus isolates from SSTIs in children. Two hundred isolates from patients with a single SSTI and 200 isolates from patients with ≥3 previous episodes from the years 2010 to 2012 were selected from an S. aureus surveillance study. Screening for retapamulin resistance was performed by the broth macrodilution method; mupirocin MICs were determined by Etest. PCR was performed for the presence of the smr gene associated with elevated MICs/minimum bactericidal concentrations (MBCs) to chlorhexidine. Among the isolates screened, 38 isolates (9.5%) exhibited retapamulin resistance, of which 22 (57.9%) were methicillin-resistant S. aureus (MRSA). Two isolates (0.5%) displayed cross-resistance to retapamulin and linezolid. Thirty-nine isolates (9.8%) were found to have mupirocin resistance. smr-positive S. aureus accounted for 14% of isolates. The proportion of smr-positive organisms increased during the study (P = 0.005). The prevalence of in vitro resistance to topical antimicrobials among S. aureus isolates causing SSTI in healthy children in our community is almost 10%. Retapamulin resistance was associated with cross-resistance to linezolid in 0.5% of isolates. In addition, there was an increase in the proportion of smr-positive isolates. Further research including clinical correlations with these findings is warranted.

Staphylococcus aureus resistance to mupirocin is often caused by acquisition of a novel isoleucyl-tRNA synthetase encoded on the plasmid gene mupA. We tested S. aureus isolates from children at Texas Children's Hospital with recurrent skin and soft tissue infections for mupirocin resistance and mupA. Of 136 isolates, 20 were resistant to mupirocin (14.7%). Fifteen isolates (11%) carried mupA, and the gene was more common in methicillin-susceptible S. aureus (21.4%) than methicillin-resistant S. aureus (8.3%; P=0.03). Seven of 20 mupirocin-resistant isolates displayed clindamycin resistance.