Staphylococcus aureus AbcA transporter enhances persister formation under ß-lactam exposure.

We evaluated the role of Staphylococcus aureus AbcA transporter in bacterial persistence and survival following exposure to the bactericidal agents nafcillin and oxacillin at both the population and single-cell levels. We show that AbcA overexpression resulted in resistance to nafcillin but not oxacillin. Using distinct fluorescent reporters of cell viability and AbcA expression, we found that over 6-14 hours of persistence formation, the proportion of AbcA reporter-expressing cells assessed by confocal microscopy increased sixfold as cell viability reporters decreased. Similarly, single-cell analysis in a high-throughput microfluidic system found a strong correspondence between antibiotic exposure and AbcA reporter expression. Persister cells grown in the absence of antibiotics showed neither an increase in nafcillin MIC nor in abcA transcript levels, indicating that survival was not associated with stable mutational resistance or abcA overexpression. Furthermore, persister cell levels on exposure to 1×MIC and 25×MIC of nafcillin decreased in an abcA knockout mutant. Survivors of nafcillin and oxacillin treatment overexpressed transporter AbcA, contributing to an enrichment of the number of persisters during treatment with pump-substrate nafcillin but not with pump-non-substrate oxacillin, indicating that efflux pump expression can contribute selectively to the survival of a persister population.

Lowering Cranioplasty Infection Incidence with Novel Bone Flap Storage Protocol: A Retrospective Cohort Study.

BACKGROUND: After craniectomy, autologous bone flaps may be stored using wet or dry cryopreservation. After brain edema subsides, they are replaced during an operation termed cranioplasty. Cranioplasty is associated with 15% infection incidence. METHODS: We conducted a retrospective comparison of infection outcomes between wet and dry cryopreservation of cranioplasty bone flaps. Historically, bone flaps were stored utilizing wet cryopreservation-bone flap storage in 1 L of lactated Ringer's solution containing 80 mg gentamicin and 2 g nafcillin in a sterile plastic container secured in an unsterile plastic bag. Our newer dry cryopreservation protocol involved storage in gauze soaked in 80 mg gentamicin and 2 g nafcillin within a 3-layer sterile bag system. RESULTS: A total of 119 autologous bone flaps were included, with median follow-up of 3.9 months from cranioplasty. Overall, 10.9% became infected, requiring subsequent surgery; 18.4% of 49 bone flaps stored using wet cryopreservation became infected compared with only 5.7% of 70 dry cryopreservation bone flaps (P = 0.038; relative risk [RR] 0.311; absolute risk reduction 12.7%). Tobacco use (P = 0.076; RR 3.17) was not associated with increased infection risk. Infection incidence was similar for traumatic craniectomy indications compared to the other indications (12.0% trauma vs. 10.1% other; P = 0.750). On average, infected cranioplasty patients spent 8.5 more days hospitalized and faced increased risk of additional complications. CONCLUSIONS: Dry cryopreservation significantly decreases infection after cranioplasty when compared with wet cryopreservation, and this mitigates additional morbidity, mortality, and costs attributable to cranioplasty infection. Other nonmodifiable risk factors for cranioplasty infection were identified.

Nafcillin Augmentation of Daptomycin and Cathelicidin LL-37 Killing of Methicillin-resistant Staphylococcus epidermidis: Foundations of Successful Therapy of Endocarditis.

Methicillin-resistant Staphylococcus epidermidis (MRSE) endocarditis failing conventional therapy has been successfully treated with nafcillin plus daptomycin in the clinic. In vitro studies showed that nafcillin enhanced daptomycin killing of MRSE in both planktonic cells and biofilm. Nafcillin exposure also sensitized MRSE to killing by human neutrophils and cathelicidin antimicrobial peptide LL-37. Fluorescent microscopy showed increased daptomycin and LL-37 binding to the MRSE bacterial surface upon nafcillin treatment. Ceftaroline also increased MRSE killing by daptomycin in planktonic cultures and biofilms, as well as daptomycin and LL-37 binding on the bacterial surface. Nafcillin, ceftaroline, and possibly other ß-lactams, may serve an important role in the therapy of MRSE endocarditis through augmentation of cationic peptide, the innate immune system, and daptomycin killing. Clinical studies will be needed to determine how early these regimens should be deployed to optimize clinical outcome.

Frequency of drug-induced liver injury in children receiving anti-staphylococcal penicillins.

INTRODUCTION: Anti-staphylococcal penicillins (ASPs) are among the most commonly prescribed antibiotics in children and are associated with a risk of drug-induced liver injury (DILI). Despite the frequent use of ASPs in children, there is no consensus on whether liver function tests (LFTs) should be routinely monitored during treatment. OBJECTIVES: To review the literature on the frequency of ASP-related DILI in children to determine the incidence, risk factors and outcomes of hepatotoxicity. METHODS: PubMed, MEDLINE and Embase were searched in January 2022 for original studies of children who received cloxacillin, dicloxacillin, flucloxacillin, methicillin, nafcillin or oxacillin that included ≥10 children aged up to 18 years, and presented data on the incidence of DILI in children exposed to ASPs. RESULTS: Overall, two studies of oral flucloxacillin, two of intravenous (IV) methicillin, three of IV nafcillin and four of IV oxacillin were included. The mean onset of DILI ranged between 7.0 and 19.0 days following commencement of antibiotic treatment and all episodes resolved between 14.2 and 16.0 days after drug discontinuation, with no specific treatment required. This review found that the incidence of DILI in children was 1 in 50 000 for oral flucloxacillin and ranged from 1 in 3 to 13 for IV oxacillin, methicillin and nafcillin. CONCLUSIONS: This review found that routine LFT monitoring is not required in children receiving low dose oral flucloxacillin in a primary care setting, although pharmacovigilance is critical. For IV preparations, the existing data support routine LFT monitoring in those receiving treatment for at least 7 days.

Comparison of Clinical Outcomes for Glycopeptides and Beta-Lactams in Methicillin-Susceptible Staphylococcus Aureus Bloodstream Infections.

PURPOSE: This study aimed to provide compelling evidence of anti-staphylococcal beta-lactam use for methicillin-susceptible Staphylococcus aureus bloodstream infection (MSSA BSI). MATERIALS AND METHODS: We retrospectively collected data on patients with MSSA BSI who were admitted to two academic tertiary-care hospitals from 2010 to 2018. Only patients who received nafcillin, cefazolin, vancomycin, or teicoplanin as definitive therapy were included. The primary outcome was 28-day mortality. To perform unbiased comparisons between both treatments, we used inverse probability of treatment weighting (IPTW) analysis. RESULTS: A total of 359 patients were divided into two groups based on the definitive therapy used: beta-lactams (n=203), including nafcillin or cefazolin; and glycopeptides (n=156), including vancomycin or teicoplanin. In the IPTW analysis, glycopeptides were associated with significantly increased odds of 28-day mortality (adjusted odds ratio, 3.37; 95% confidence interval, 1.71-6.61; p<0.001). The rate of primary outcome in prespecified subgroups was largely consistent with the main analysis. CONCLUSION: Definitive therapy with beta-lactams in patients with MSSA BSI was associated with lower 28-day mortality compared to definitive therapy with glycopeptides.

PEG-grafted liposomes for enhanced antibacterial and antibiotic activities: An in vivo study.

Staphylococcus aureus (S. aureus) biofilm-associated infections are a primary concern for public health worldwide. Current therapeutics cannot penetrate the biofilms efficiently, resulting in low drug concentrations at the infected sites and increasing the frequency of drug usage. To solve this issue, nanotechnology platforms seem to be a promising approach. In this study, the potential therapeutic effects of (PEG)ylated liposome (PEG-Lip) for the delivery of nafcillin (NF) antibiotic were assessed. The results demonstrated that NF-loaded liposome (Lip-NF) and NF-loaded PEG-Lip (PEG-Lip-NF) released 76.4 and 62% of the loaded NF, respectively, in a controlled manner after 50 h. Also, it was found that PEG-Lip-NF, compared to Lip-NF and NF, was more effective against a methicillin-susceptible S. aureus (MSSA; minimum inhibitory concentration (MIC): 1.0 ± 0.03, 0.5 ± 0.02, and 0.25 ± 0.01 µg/mL; and minimum biofilm inhibitory concentration (MBIC50): 4.0 ± 0.18, 1.0 ± 0.04, and 0.5 ± 0.02 µg/mL for NF, Lip-NF, and PEG-Lip-NF, respectively). PEG-Lip-NF, compared to NF and Lip-NF, could also more efficiently decrease the side effects of NF through improving human MG-63 osteoblast cell viability (cell viability at 100 µM of NF: 76, 68, and 38% for PEG-Lip-NF, Lip-NF, and NF, respectively). PEG-Lip-NF, compared to control, NF, and Lip-NF groups, was more efficacious by 45, 25, and 10%, respectively, to decrease the virulence of MSSA bacteremia through inhibiting the weight loss of the infected mice. Also, PEG-Lip-NF and Lip-NF, compared to control and NF groups, caused a considerable decrease in the mortality rate in a murine model of bacteremia (number of dead mice: 0, 0, 2, and 8 out of 15 for PEG-Lip-NF, Lip-NF, NF, and control groups, respectively). Overall, the results of this study demonstrated that the loading of NF into PEG-Lip is a promising strategy to decrease the side effects of NF with improved antibacterial effects for the treatment of MSSA biofilm-associated infections.

Safety and Efficacy of Nafcillin for Empiric Therapy of Late-Onset Sepsis in the NICU.

BACKGROUND AND OBJECTIVE: In 2014 at Nationwide Children's Hospital, the Neonatal Antimicrobial Stewardship Program recommended nafcillin over vancomycin for empirical therapy of possible late-onset sepsis (LOS) in infants without a history of methicillin-resistant Staphylococcus aureus colonization or infection. We report our experience with this guideline and assess its safety. METHODS: We retrospectively reviewed all infants who received nafcillin or vancomycin for empirical treatment of possible LOS at 3 NICUs before (January 2013-May 2014) and after (January 2017-March 2019) implementation of a vancomycin reduction guideline. Safety measures included duration of blood culture positivity, recurrence of infection with the same previously identified pathogen in the 14 days after discontinuation of antibiotic therapy, and mortality. RESULTS: Among 366 infants who received a first antibiotic course for possible LOS, 84% (95 of 113) and 25% (62 of 253) received empirical therapy with vancomycin before and after the guideline implementation, respectively, representing a 70% reduction. Nafcillin use increased by 368%. Duration of blood culture positivity did not differ before and after the guidance. In 2 infants, antibiotic therapy was restarted within 14 days of discontinuation of the initial therapy for recurrence of the same infection; both had received empirical vancomycin. Overall in-hospital mortality was 10%, and there was no difference before (9%) and after (10%) implementation of the vancomycin reduction guidance (odds ratio, 0.97). CONCLUSIONS: Nafcillin can be a safe alternative to vancomycin for empirical therapy of LOS among NICU infants who do not have a history of methicillin-resistant S aureus infection or colonization.

Tolerability of Cefazolin in Nafcillin-Intolerant Patients for the Treatment of Methicillin-Susceptible Staphylococcus aureus Infections.

BACKGROUND: Non-immunoglobulin E (IgE)-mediated hypersensitivity reactions (HSRs) to nafcillin are commonly reported, but scarce data are available to guide appropriate antibiotic change following these reactions. Although cefazolin is an attractive therapeutic alternative in methicillin-susceptible Staphylococcus aureus (MSSA) infections when patients experience an HSR to nafcillin, more data are needed to evaluate the tolerability of cefazolin after switching from nafcillin. The purpose of this study was to describe the tolerability of cefazolin in patients who develop a suspected non-IgE-mediated HSR to nafcillin. METHODS: This was a retrospective, descriptive case series of patients who received nafcillin for an MSSA infection, experienced a suspected non-IgE-mediated HSR, and were switched to cefazolin between October 2015 and November 2019 at a single academic medical center. The primary objective was to identify the percentage of patients who completed cefazolin after experiencing a suspected non-IgE-mediated HSR to nafcillin. RESULTS: There were 80 patients with 87 prespecified non-IgE-mediated HSRs during the study period. Seventy-one (89%) patients completed cefazolin, with 53 (75%) of these patients completing at least 2 weeks of therapy. One patient was ultimately switched from cefazolin to daptomycin due to concern for treatment failure. Eight patients (10%) did not tolerate cefazolin after switching from nafcillin. Of these, 3 patients experienced an unrelated HSR, whereas 5 patients experienced the same non-IgE-mediated HSR that was attributed to nafcillin and discontinued cefazolin within 7 days. The most common HSR cited was immune-mediated nephritis; however, the majority were clinically presumed but did not meet objective diagnostic criteria. CONCLUSIONS: Treatment with cefazolin after experiencing a suspected non-IgE-mediated HSR to nafcillin appears to be safe, even for patients requiring a prolonged duration of cefazolin.

Comparison of Nafcillin and Cefazolin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia.

BACKGROUND: Traditionally, the antibiotic of choice for Methicillin-susceptible Staphylococcus aureus related blood stream infections (MSSA-BSI) are the antistaphylococcal penicillins. Cefazolin is considered an alternative agent, with recent evidence showing similar clinical efficacy. This study further evaluates the utility of nafcillin versus cefazolin in MSSA bacteremia including high disease burden sources of infection and its impact on treatment failure. METHODS: This retrospective study included patients admitted to Methodist LeBonheur Healthcare adult hospitals from 2011 to 2016. Patients were included if they received at least 3 days of either nafcillin or cefazolin and had a positive blood culture for MSSA. The primary objective was to evaluate rates of treatment failure between groups. Secondary outcomes included clinical and microbiological cure, MSSA-BSI associated readmissions, identification of risk factors for treatment failure including disease burden, in-hospital and 90 day mortality. RESULTS: A total of 277 patients were included (nafcillin n = 126; cefazolin n = 151). Treatment failure and microbiologic cure were similar between nafcillin and cefazolin (20.6% vs. 16.6%; 91.2% vs. 87.2%, respectively). Clinical cure was significantly higher in the cefazolin treatment arm (93.4 vs. 83.3%; P = 0.012). However, the total number of patients with high disease burden was greater in the nafcillin group (54.8% vs. 39.1%; P = 0.011). Higher rates of in-hospital mortality were observed in the nafcillin group (15.1% vs. 6%; P = 0.016). CONCLUSIONS: Our study observed significantly higher rates of clinical cure and reduced in-hospital mortality in patients who received cefazolin. Further analysis is warranted to evaluate the effectiveness of these agents and identifying predictors of treatment failure.

Nafcillin degradation by heterogeneous electro-Fenton process using Fe, Cu and Fe/Cu nanoparticles.

Heterogeneous electro-Fenton (HEF) is as an alternative to the conventional electro-Fenton (EF) process. HEF uses a solid phase catalyst, whereas EF employs a solubilized one. This implies that in HEF, material can be recovered through a simple separation process such as filtration or magnetic separation in HEF. HEF also has the advantage of not requires a previous pH adjustment, which facilitates working in a higher pH range. In this work, Fe, Cu and Fe/Cu bimetallic nanoparticles (Fe/Cu NPs) were synthesized, characterized and used for the degradation of Nafcillin (NAF). The effect of the adsorption and the anodic oxidation (AO-H2O2) process was tested to assess their influence on HEF. NAF adsorption did not exceed 24% of antibiotic removal and the AO-H2O2 process eliminated the total NAF after 240 min of electrolysis. Through the HEF process, the antibiotic was completely removed using Fe/Cu NPs after 7.0 min of electrolysis, while these NPs, mineralization reached 41% after 240 min. In this case, NAF degradation occurs mainly due to the generation of hydroxyl radicals in the BDD electrode, and the Fenton reaction with Fe and Cu NPs. The main organic intermediates produced during the degradation of NAF by HEF were identified allowing the proposal of degradation pathway. Finally, the antibiotic was also completely eliminated from a wastewater from slaughterhouse after 15 min of treatment by HEF and using Fe/Cu bimetallic NPs.

Retrospective Analysis of Adverse Drug Events Between Nafcillin Versus Cefazolin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections.

Background: Nafcillin or cefazolin are drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) infections. Prior studies indicate a higher incidence of acute kidney injury (AKI) with nafcillin, although AKI classification and time to occurrence is not well described. Objective: To characterize the incidence and time to adverse drug events for nafcillin versus cefazolin in the inpatient setting. Methods: A retrospective cohort study evaluated hospitalized, adult patients receiving intravenous nafcillin or cefazolin for treatment of MSSA infection. Incidence and time to AKI based on RIFLE criteria were measured. Secondary end points included antibiotic discontinuation and incidence of neutropenia, thrombocytopenia, elevated transaminases, and Clostridioides difficile infection (CDI). Results: Of 324 patients who received nafcillin (n = 119) or cefazolin (n = 205), higher rates of AKI were found for nafcillin versus cefazolin (19% vs 2%, respectively; P < 0.0001). Median time to AKI with nafcillin was 6.5 days (range, 3-14 days). The majority of patients were classified as RIFLE "Risk" stratum. Nafcillin treatment discontinuations were more frequent than for cefazolin (17.6% vs 0.9%, respectively; P < 0.0001). Nafcillin was an independent predictor of AKI (odds ratio = 12.4; 95% CI = 4.14-47.60, P < 0.0001). No differences in neutropenia, thrombocytopenia, elevated transaminases, or CDI were observed. Conclusion and Relevance: Nafcillin displayed higher rates of AKI at a median of 1 week of therapy, which provides a framework for clinician monitoring and consideration of antibiotic modification. Most patients developed "Risk" class AKI (RIFLE classification), which may be reversible with prompt intervention.

A comparison of safety and outcomes with cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus bloodstream infections.

BACKGROUND: Methicillin-susceptible Staphylococcus aureus (MSSA) is a frequent cause of bloodstream infections (BSI). Treatment with nafcillin (NAF) has been preferred to cefazolin (CFZ). However, comparable outcomes have been found with CFZ with possibly lower risk for side-effects. This study compared safety and effectiveness of NAF versus CFZ for MSSA BSI. METHODS: This single center retrospective study evaluated adults admitted with MSSA BSI who received NAF or CFZ. Patients receiving ≥24 h of antibiotics were included for safety analyses. Patients receiving NAF or CFZ for ≥75% of a 14 day minimum treatment course were assessed for clinical effectiveness. The primary safety outcome was incidence of renal toxicity with multiple secondary safety endpoints. Clinical success was defined as symptom resolution, repeat negative cultures, lack of additional therapy for presumed failure, and lack of recurrence within 30 days. RESULTS: A total of 130 patients receiving NAF (n = 79) or CFZ (n = 51) were included for safety analysis. Of those, 90 met criteria for effectiveness assessment (NAF n = 40, CFZ n = 50). Baseline characteristics were well matched. NAF was associated with a higher incidence of nephrotoxicity compared to CFZ (25% vs. 2%, RR 1.31, 95% CI 1.15-1.5, p < 0.001), allergic reactions (p = 0.01) and a trend for hepatotoxicity (p = 0.08). Clinical success was achieved in 82% NAF and 94% CFZ treated patients (p = 0.1). CONCLUSION: CFZ was associated with less nephrotoxicity and no difference in clinical success compared to NAF for MSSA BSI. A prospective study comparing NAF to CFZ for MSSA BSI should be conducted to elucidate differences in therapies.

Disproportionality Analysis of Safety with Nafcillin and Oxacillin with the FDA Adverse Event Reporting System (FAERS).

Antistaphylococcal penicillins such as nafcillin and oxacillin are among the first choices of treatment for severe invasive methicillin-susceptible Staphylococcus aureus (MSSA) infections, although there has been limited safety evaluations between individual agents. Using the FDA Adverse Event Reports System (FAERS), oxacillin was observed to have a lower proportion of reports of acute renal failure (reporting odds ratio [ROR], 5.3 [95% confidence interval {CI}, 3.1 to 9.3] versus 21.3 [95% CI, 15.8 to 28.6], respectively) and hypokalemia (ROR, 0.7 [95% CI, 0.1 to 4.8] versus 11.4 [95% CI, 7.1 to 18.3], respectively) than nafcillin.

Profiling the effect of nafcillin on HA-MRSA D712 using bacteriological and physiological media.

Staphylococcus aureus strains have been continuously evolving resistance to numerous classes of antibiotics including methicillin, vancomycin, daptomycin and linezolid, compounding the enormous healthcare and economic burden of the pathogen. Cation-adjusted Mueller-Hinton broth (CA-MHB) is the standard bacteriological media for measuring antibiotic susceptibility in the clinical lab, but the use of media that more closely mimic the physiological state of the patient, e.g. mammalian tissue culture media, can in certain circumstances reveal antibiotic activities that may be more predictive of effectiveness in vivo. In the current study, we use both types of media to explore antibiotic resistance phenomena in hospital-acquired USA100 lineage methicillin-resistant, vancomycin-intermediate Staphylococcus aureus (MRSA/VISA) strain D712 via multidimensional high throughput analysis of growth rates, bacterial cytological profiling, RNA sequencing, and exo-metabolomics (HPLC and LC-MS). Here, we share data generated from these assays to shed light on the antibiotic resistance behavior of MRSA/VISA D712 in both bacteriological and physiological media.

Characterization of CA-MRSA TCH1516 exposed to nafcillin in bacteriological and physiological media.

Cation adjusted-Mueller Hinton Broth (CA-MHB) is the standard bacteriological medium utilized in the clinic for the determination of antibiotic susceptibility. However, a growing number of literature has demonstrated that media conditions can cause a substantial difference in the efficacy of antibiotics and antimicrobials. Recent studies have also shown that minimum inhibitory concentration (MIC) tests performed in standard cell culture media (e.g. RPMI and DMEM) are more indicative of in vivo antibiotic efficacy, presumably because they are a better proxy for the human host's physiological conditions. The basis for the bacterial media dependent susceptibility to antibiotics remains undefined. To address this question, we characterized the physiological response of methicillin-resistant Staphylococcus aureus (MRSA) during exposure to sub-inhibitory concentrations of the beta-lactam antibiotic nafcillin in either CA-MHB or RPMI + 10% LB (R10LB). Here, we present high quality transcriptomic, exo-metabolomic and morphological data paired with growth and susceptibility results for MRSA cultured in either standard bacteriologic or more physiologic relevant medium.

Subinhibitory concentrations of tedizolid potently inhibit extracellular toxin production by methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

PURPOSE: Potent extracellular toxins including alpha-haemolysin, Panton-Valentine leukocidin (PVL) and toxic-shock syndrome toxin 1 (TSST-1) significantly contribute to Staphylococcus aureus pathogenesis, thus, toxin suppression is a primary focus in treatment of staphylococcal disease. S. aureus maintains complex strategies to regulate toxin expression and previous data have demonstrated that subinhibitory concentrations of beta-lactam antibiotics can adversely increase S. aureus exotoxin production. The current study evaluates the effects of subinhibitory concentrations of tedizolid, a second-generation oxazolidinone derivative, on expression of staphylococcal exotoxins in both methicillin-resistant and methicillin-sensitive S. aureus. METHODOLOGY: S. aureus exotoxin expression levels were compared at 12 and 24 h following treatment with tedizolid, linezolid, nafcillin or vehicle control. RESULTS: Our findings show that the level of antibiotic required to alter toxin production was strain-dependent and corresponds with the quantity of toxin produced, but both tedizolid and linezolid could effectively reduce expression of alpha-haemolysin, PVL and TSST-1 toxin at subinhibitory concentrations. In contrast, nafcillin showed less attenuation and, in some S. aureus strains, led to an increase in toxin expression. Tedizolid consistently inhibited toxin production at a lower overall drug concentration than comparator agents. CONCLUSION: Together, our data support that tedizolid has the potential to improve outcomes of infection due to its superior ability to inhibit S. aureus growth and attenuate exotoxin production.

Vancomycin associated acute kidney injury in pediatric patients.

INTRODUCTION: Vancomycin associated acute kidney injury (vAKI) is a well known complication in pediatric patients. Identification and characterization of the incidence and risk factors for vAKI in the pediatric population would assist clinicians in potentially preventing or mitigating vAKI. METHODS AND MATERIALS: A 6 year retrospective cohort study was designed. Patients were included if they were < 19 years of age, received vancomycin as inpatients, and had a baseline SCr and one other SCr drawn during and up to 72 hours after the discontinuation of vancomycin. Data collection included patient demographics, vancomycin doses and length of therapy, vancomycin serum concentrations, and concomitant medications. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to characterize acute kidney injury. Descriptive statistical methods were used and ordinal logistic regression was employed to determine variables significantly associated with vAKI. RESULTS: A total of 7,095 patients met study criteria (55.4% male, median age 4.1 years (IQR 0.67-11.2 years)). Mechanical ventilation was used in 7.9% (n = 563) and mortality was 4.9% (n = 344). A total of 153 concomitant medications were identified. A median of 5 (IQR 3-7) SCr values were obtained and median SCr prior to vancomycin was 0.39 (IQR 0.28-0.57) mg/dL (CrCl 134±58 mL/min/1.73m2). Vancomycin was administered for a median of 2 (IQR 1-3) days (14.9±1.6 mg/kg/dose). vAKI was present in 12.2% (n = 862: KDIGO stage 1 (8.30%, n = 589), KDIGO stage 2 (1.94%, n = 138) KDIGO stage 3 (1.89%, n = 134)). Mean vancomycin serum concentration at 6-8 hours after a dose for patients with vAKI (10.7±8.9 mg/L) was significantly, but not clinically different for patients with no vAKI (7.5±6.3 mg/L). (p<0.05) Ordinal logistic regression identified total dose of vancomycin, vancomycin administration in the intensive care unit, and concomitant medication administration as significant for vAKI. In particular, concomitant administration of several different medications, including nafcillin, clindamycin, and acetazolamide, were noted for strong associations with vAKI. (p<0.05). CONCLUSIONS: Moderate to severe acute kidney injury due to vancomycin is infrequent in children and associated with concomitant medication use and total dose of vancomycin. Serum vancomycin concentrations are not useful predictors of vAKI in the pediatric population.

Septic arthritis of native hip joint by Staphylococcus lugdunensis: a case report.

Staphylococcus lugdunensis is a rare virulent coagulase-negative staphylococcus (CoNS) that behaves similarly to Staphylococcus aureus in causing deep abscesses, skin and soft tissue infections, and central nervous system infections. Additionally, there can be certain blood stream infections including sepsis, septic shock, toxic shock syndrome, and endocarditis complicated by embolic events. Reports of septic arthritis of a native joint associated with this organism have been infrequent, justifying the presentation and discussion of this case.

Septic arthritis of native hip joint by Staphylococcus lugdunensis: a case report

Abstract Staphylococcus lugdunensis is a rare virulent coagulase-negative staphylococcus (CoNS) that behaves similarly to Staphylococcus aureus in causing deep abscesses, skin and soft tissue infections, and central nervous system infections. Additionally, there can be certain blood stream infections including sepsis, septic shock, toxic shock syndrome, and endocarditis complicated by embolic events. Reports of septic arthritis of a native joint associated with this organism have been infrequent, justifying the presentation and discussion of this case.