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.

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.

Comparison of the efficacy of nafcillin and glycopeptides as definitive therapy for patients with methicillin-susceptible Staphylococcus aureus bacteremia: a retrospective cohort study.

BACKGROUND: Studies have shown that the prognosis of the treatment of methicillin-susceptible S. aureus (MSSA) with glycopeptides is inferior compared to treatment with ß-lactam. However, there are only few studies comparing treatment with antistaphylococcal penicillin alone to glycopeptide treatment. The aim of this study was to compare the efficacy of nafcillin, an antistaphylococcal penicillin, with that of glycopeptides as a definitive therapy for MSSA bacteremia. METHODS: Patients with MSSA bacteremia recruited from a tertiary referral hospital were enrolled in this retrospective cohort study. Demographic characteristics, laboratory data, and clinical outcome of the treatment were compared between a group receiving nafcillin and a group receiving glycopeptides. RESULTS: A total of 188 patients with MSSA bacteremia were included in this study. The glycopeptide group had a higher rate of malignancy (28.6 vs. 60.8%, p < 0.001) and proportion of healthcare-associated infections (47.3 vs. 72.2%, p < 0.001) compared to the nafcillin group. The ratio of skin and soft tissue infections (30.0 vs. 16.7%, p = 0.037) and bone and joint infections (17.8 vs. 6.3%, p = 0.022), as well as levels of C-reactive protein (139.60 vs. 107.61 mg/dL, p = 0.022) were higher in the nafcillin group. All-cause 28-day mortality was significantly high in the glycopeptide group (7.7 vs. 20.6%, p = 0.013). CONCLUSION: In patients with MSSA bacteremia, all-cause 28-day mortality rate was higher in a group treated with glycopeptides than in a group treated with nafcillin. Therefore, the use of nafcillin should be considered as a definitive therapy for MSSA bacteremia.

Does the Beta-Lactam Matter? Nafcillin versus Cefazolin for Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections.

BACKGROUND: Antistaphylococcal penicillins have historically been regarded as the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). However, recent outcomes data compared to cefazolin treatment are conflicting. OBJECTIVE: This study compared treatment failure and adverse effects associated with nafcillin and cefazolin for MSSA BSI. METHODS: Adult inpatients with MSSA BSI between January 1, 2009 and August 31, 2015 were included in this retrospective cohort study if they received ≥72 h of nafcillin or cefazolin as directed therapy after no more than 72 h of any empiric therapy. The primary composite endpoint was treatment failure defined by clinician documentation, 30-day recurrence of infection, all-cause 30-day in-hospital mortality, or loss to follow-up. Secondary outcomes included antibiotic-related acute kidney injury (AKI), acute interstitial nephritis (AIN), hepatotoxicity, and rash. RESULTS: Among 157 patients, 116 (73.9%) received nafcillin and 41 (26.1%) received cefazolin. The baseline characteristics were similar except cefazolin-treated patients had higher APACHE II scores and more frequent renal dysfunction. No difference in the composite treatment failure outcome (28.4 vs. 31.7%; p = 0.69) was detected between the nafcillin and cefazolin groups, respectively. In a sensitivity analysis excluding patients without known follow-up, there was no significant difference of treatment failure. AKI, AIN, hepatotoxicity, and rash were all numerically more frequent among nafcillin-treated patients. CONCLUSIONS: Among nafcillin- or cefazolin-treated patients with MSSA BSI, there was no significant difference in treatment failure. Observing more frequent presumptive adverse effects associated with nafcillin receipt, future prospective studies evaluating cefazolin appear warranted.

Efficacy of Ceftaroline against Methicillin-Susceptible Staphylococcus aureus Exhibiting the Cefazolin High-Inoculum Effect in a Rat Model of Endocarditis.

Certain Staphylococcus aureus strains exhibit an inoculum effect (InE) with cefazolin (CFZ) that has been associated with therapeutic failures in high-inoculum infections. We assessed the in vitro activities of ceftaroline (CPT), CFZ, and nafcillin (NAF) against 17 type A ß-lactamase (ßla)-producing, methicillin-susceptible S. aureus (MSSA) strains, including the previously reported TX0117, which exhibits the CFZ InE, and its ßla-cured derivative, TX0117c. Additionally, we determined the pharmacokinetics of CPT in rats after single intramuscular doses of 20 and 40 mg/kg of body weight and evaluated the activities of CPT (40 mg/kg every 8 h [q8h]), CFZ, and NAF against TX0117 and TX0117c in a rat model of infective endocarditis. No InE was observed for CPT or NAF, whereas a marked InE was detected for CFZ (MIC, 8 to ≥128 µg/ml). CPT and NAF treatment against TX0117 resulted in mean bacterial counts of 2.3 and 2.1 log10 CFU/g in vegetations, respectively, compared to a mean of 5.9 log10 CFU/g in the CFZ-treated group (CPT and NAF versus CFZ, P = 0.001; CPT versus NAF, P = 0.9830). Both CFZ and CPT were efficacious against the ßla-cured derivative, TX0117c, compared to time zero (t0) (P = <0.0001 and 0.0015, respectively). Our data reiterate the in vivo consequences of the CFZ InE and show that CPT is not affected by this phenomenon. CPT might be considered for high-inoculum infections caused by MSSA exhibiting the CFZ InE.

Tacrolimus interaction with nafcillin resulting in significant decreases in tacrolimus concentrations: A case report.

Tacrolimus (TAC) is subject to many drug interactions as a result of its metabolism primarily via CYP450 isoenzyme 3A4. Numerous case reports of TAC and CYP3A4 inducers and inhibitors have been described including antimicrobials, calcium channel antagonists, and antiepileptic drugs. We present the case of a 13-year-old patient with cystic fibrosis and a history of liver transplantation, where subtherapeutic TAC concentrations were suspected to be a result of concomitant TAC and nafcillin (NAF) therapy. The observed drug interaction occurred on two separate hospital admissions, during both of which the patient exhibited therapeutic TAC concentrations prior to exposure to NAF, a CYP3A4 inducer. Upon discontinuation of NAF, TAC concentrations recovered in both instances. This case represents a drug-drug interaction between TAC and NAF that has not previously been reported to our knowledge. Despite the lack of existing reports of interaction between these two agents, this case highlights the importance of therapeutic drug monitoring and assessing for any potential drug-drug or drug-food interactions in patients receiving TAC therapy.

Reversion From Methicillin Susceptibility to Methicillin Resistance in Staphylococcus aureus During Treatment of Bacteremia.

Approximately 3% of Staphylococcus aureus strains that, according to results of conventional phenotypic methods, are highly susceptible to methicillin-like antibiotics also have polymerase chain reaction (PCR) results positive for mecA. The genetic nature of these mecA-positive methicillin-susceptible S. aureus (MSSA) strains has not been investigated. We report the first clearly defined case of reversion from methicillin susceptibility to methicillin resistance among mecA-positive MSSA within a patient during antibiotic therapy. We describe the mechanism of reversion for this strain and for a second clinical isolate that reverts at a similar frequency. The rates of reversion are of the same order of magnitude as spontaneous resistance to drugs like rifampicin. When mecA is detected by PCR in the clinical laboratory, current guidelines recommend that these strains be reported as resistant. Because combination therapy using both a ß-lactam and a second antibiotic suppressing the small revertant population may be superior to alternatives such as vancomycin, the benefits of distinguishing between mecA-positive MSSA and MRSA in clinical reports should be evaluated.

Cefazolin versus Nafcillin for Methicillin-Sensitive Staphylococcus aureus Bloodstream Infection in a California Tertiary Medical Center.

Recent observational studies have suggested possible reductions in mortality in patients receiving cefazolin versus antistaphylococcal penicillins. We examined 90-day mortality in patients receiving cefazolin compared to nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infection (BSI). We identified persons with MSSA BSI admitted to San Francisco General Hospital from January 2008 to July 2013 through a hospital-wide infection surveillance system and confirmed 90-day mortality using U.S. national vital registries. We included persons receiving cefazolin or nafcillin as the predominant intravenous antimicrobial agent; all participants received inpatient Infectious Diseases service consultation. We estimated the association between receipt of cefazolin and 90-day risk of death by multivariate logistic regression, including a propensity score for receiving cefazolin as the second predictor. Of 230 MSSA BSI cases, 30 received nafcillin and 70 received cefazolin as the predominant antimicrobial; 10 died within 90 days, 5 from each group. Unadjusted analysis showed substantial but not statistically significant reduced odds of death in those receiving cefazolin (odds ratio, 0.38; 95% confidence interval [CI], 0.10 to 1.44). Multivariate analysis with propensity scores found a similar adjusted odds ratio (0.40; 95% CI, 0.09 to 1.74; P = 0.22). We found a large reduction in 90-day mortality in those receiving cefazolin compared to nafcillin for MSSA BSI, but this finding was not statistically significant. The magnitude of effect seen in this and other studies justifies further study.

Rapidly Progressive Seeding of a Community Acquired Pathogen in an Immune-competent Host--End Organ Damage from Head to Bone.

This report describes a 64-years-old male patient that presented to our hospital with a chief complaint of acute worsening of his usual chronic lower back pain, progressive weakness in lower extremities and subjective fevers at home. Spine CT failed to demonstrate any infectious foci but showed partially visualized lung cavitary lesion and renal pole abnormalities. Blood cultures grew methicillin-sensitive Staphylococcus Aureus (MSSA). Transthoracic echocardiogram (TTE) showed no signs of infective endocarditis (IE). Later, the patient experienced an acute deterioration on clinical status and examination showed development of a new murmur. He also developed new hemiparesis with up-going babinski reflex. A head MRI showed multiple infarcts. MRI spine displayed osteomyelitis at T12-L1. Cerebro-spinal fluid was positive for meningitis. A transesophageal echocardiogram (TEE) was performed demonstrating new severe mitral and mild tricuspid regurgitations with a definitive 1.5 cm mobile vegetation on posterior mitral leaflet. We present is a very interesting case of a rapidly progressive MSSA infection. MSSA meningitis is a rare disease; there are only few reported cases in the literature to date. We describe a case of MSSA bacteremia, of questionable source, that resulted in MSSA endocarditis affecting right and left heart in a patient who did not have a history of intravenous drug use (IVDU) or immunosuppression. The case was complicated by septic emboli to systemic circulation involving the kidneys, vertebral spine (osteomyelitis), lungs and brain with consequent meningitis and stroke. Even when MSSA infections are well known, to our knowledge there are no previous case reports describing such an acute-simultaneous-manifestation of multi-end-organ failure, including meningitis and stroke. These latter are rarely reported, even individually.

Comparative evaluation of the tolerability of cefazolin and nafcillin for treatment of methicillin-susceptible Staphylococcus aureus infections in the outpatient setting.

BACKGROUND: Nafcillin and cefazolin are considered first-line therapy for most infections with methicillin-susceptible Staphylococcus aureus (MSSA), and recent studies have suggested similar clinical efficacy. Limited data are available on the comparative tolerability of these agents. METHODS: In this retrospective cohort analysis of patients treated with either nafcillin or cefazolin for MSSA infection in the outpatient parenteral antimicrobial therapy clinic at Massachusetts General Hospital from 2007 to 2011, the frequency of premature antimicrobial discontinuation (PAD) and drug-emergent events (DEEs) was calculated. RESULTS: Three hundred sixty-six and 119 patients were treated with nafcillin or cefazolin, respectively. The median anticipated duration of therapy was comparable at 28 (interquartile range [IQR], 16-37) and 29 (IQR, 24-39) days, respectively, for those treated with nafcillin and cefazolin. Fewer patients completed the prespecified treatment course with nafcillin than with cefazolin (PAD rate, 33.8% vs 6.7%; P < .0001). The hazard ratio for PAD in the nafcillin vs cefazolin groups was 2.81 (95% confidence interval [CI], 1.26-3.68). More patients in the nafcillin group developed rash (13.9% vs 4.2%; P = .002), renal dysfunction (11.4% vs 3.3%; P = .006), and liver function abnormalities (8.1% vs 1.6%; P = .01). Overall rates of DEEs per 1000 patient-days were 16.9 (95% CI, 10.4-27.3) and 4.8 (95% CI, 1.1-10.2), respectively. In 9 cases of nafcillin discontinuation, treatment was changed to cefazolin; all 9 completed treatment with no further observed DEEs. CONCLUSIONS: Nafcillin treatment was associated with higher rates of both PAD as well as DEEs compared with cefazolin treatment. This difference in tolerability, in addition to efficacy and cost, should be considered when decisions for outpatient parenteral MSSA treatment are made.

Tolerability of cefazolin after immune-mediated hypersensitivity reactions to nafcillin in the outpatient setting.

The objective of the present study was to assess the safety and tolerability of cefazolin therapy among patients with methicillin-sensitive Gram-positive bacterial infections who develop non-IgE-mediated hypersensitivity reactions (HSRs) to nafcillin. In this retrospective cohort analysis of the Outpatient Parenteral Antimicrobial Therapy program at the Massachusetts General Hospital from 2007 through 2013, we identified patients switched from nafcillin to cefazolin after an immune-mediated HSR. We reviewed patient demographics, details about the original HSR, and outcomes after the switch to cefazolin therapy. HSRs were classified by reaction type and likely mechanism. There were 467 patients treated with nafcillin, of which 60 (12.8%) were switched to cefazolin during their prescribed course. Of the 60 patients who transitioned to cefazolin, 17 (28.3%) were switched because of non-IgE-mediated HSRs. HSRs included maculopapular rash (n = 10), immune-mediated nephritis (n = 3), isolated eosinophilia (n = 2), immune-mediated hepatitis (n = 1), and a serum sickness-like reaction (n = 1). All but one patient (94.1%) who switched to cefazolin tolerated the drug with resolution of the HSR and completed their therapy with cefazolin. No patient experienced worsening of their rash or progressive organ dysfunction. With appropriate monitoring, therapy with cefazolin after non-IgE-mediated HSRs to nafcillin appears to be safe.

Comparative activities of telavancin combined with nafcillin, imipenem, and gentamicin against Staphylococcus aureus.

Beta-lactams enhance the killing activity of vancomycin. Due to structural and mechanistic similarities between vancomycin and telavancin, we investigated the activity of telavancin combined with nafcillin and imipenem compared to the known synergistic combination of telavancin and gentamicin. Thirty strains of Staphylococcus aureus, 10 methicillin-susceptible S. aureus (MSSA), 10 methicillin-resistant S. aureus (MRSA), and 10 heterogeneously vancomycin-intermediate S. aureus (hVISA), were tested for synergy by time-kill methodology. Six strains (2 each of MSSA, MRSA, and hVISA) were further evaluated in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model with simulated regimens of 10 mg/kg of body weight of telavancin once daily alone and combined with 2 g nafcillin every 4 h, 500 mg imipenem every 6 h, or 5 mg/kg gentamicin once daily over 72 h. In the synergy test, 67% of strains displayed synergy with the combination of telavancin and gentamicin, 70% with telavancin and nafcillin, and 63% with telavancin and imipenem. In the PK/PD model, the activities of all three combinations against MRSA and hVISA were superior to all individual drugs alone (P ≤ 0.002) and were similar to each other (P ≥ 0.187). The activities of all three combinations against MSSA were generally similar to each other except for one strain where the combination of telavancin and imipenem was superior to all other regimens (P ≤ 0.011). The activity of the combination of telavancin and beta-lactam agents was similar to that of telavancin and gentamicin against S. aureus, including resistant strains. Because beta-lactam combinations are less likely to be nephrotoxic than telavancin plus gentamicin, these beta-lactam combinations may have clinical utility.

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.

Is cefazolin inferior to nafcillin for treatment of methicillin-susceptible Staphylococcus aureus bacteremia?

About 20% of methicillin-susceptible Staphylococcus aureus (MSSA) isolates have a substantial inoculum effect with cefazolin, suggesting that cefazolin treatment may be associated with clinical failure for serious MSSA infections. There are no well-matched controlled studies comparing cefazolin with nafcillin for the treatment of MSSA bacteremia. A retrospective propensity-score-matched case-control study was performed from 2004 to 2009 in a tertiary care hospital where nafcillin was unavailable from August 2004 to August 2006. The cefazolin group (n = 49) included MSSA-bacteremic patients treated with cefazolin during the period of nafcillin unavailability, while the nafcillin group (n = 84) comprised those treated with nafcillin. Treatment failure was defined as a composite outcome of a change of antibiotics due to clinical failure, relapse, and mortality. Of 133 patients, 41 patients from each group were matched by propensity scores. There were no significant differences in baseline characteristics between the matched groups. The treatment failure rates were not significantly different at 4 or 12 weeks (10% [4/41] versus 10% [4/41] at 4 weeks [P > 0.99] and 15% [6/41] versus 15% [6/41] at 12 weeks [P > 0.99]). Cefazolin treatment was interrupted less frequently than nafcillin treatment due to drug adverse events (0% versus 17%; P = 0.02). Cefazolin had clinical efficacy similar to that of nafcillin and was more tolerable than nafcillin for the treatment of MSSA bacteremia.

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.

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.

Lysostaphin eradicates established Staphylococcus aureus biofilms in jugular vein catheterized mice.

OBJECTIVES: Staphylococcus aureus infections associated with indwelling devices can be very difficult to treat due to the recalcitrant nature of bacterial biofilms to conventional antibiotics. Lysostaphin has been shown to clear S. aureus biofilms in vitro, and in this study we determined whether lysostaphin could also eradicate established S. aureus biofilms on implanted jugular vein catheters in mice. METHODS: Jugular vein catheterized mice (four to six per group) challenged with S. aureus developed multiorgan infection and biofilm infections on the catheters. The infected mice with established biofilms received various doses of recombinant lysostaphin through the catheters, administered up to three times daily for up to 4 days. Some mice also received lysostaphin combined with nafcillin. Following treatment, mice were sacrificed and cfu on the catheter and in the liver and heart were determined. In another set of experiments, implanted jugular vein catheters in mice were pre-instilled with lysostaphin to determine whether this pre-treatment would protect the mice from biofilm infection. RESULTS AND CONCLUSIONS: Lysostaphin administered at 15 mg/kg in combination with 50 mg/kg nafcillin three times per day for 4 days eradicated established S. aureus, including methicillin-resistant S. aureus, biofilms from implanted catheters and sterilized heart and liver infections of S. aureus-infected mice. Furthermore, a single pre-instillation of 10 mg/kg lysostaphin in catheters completely protected catheterized mice from a subsequent biofilm infection. These results demonstrate that lysostaphin is an effective treatment as well as prophylaxis for S. aureus biofilms on indwelling catheters.

Epidemiology of community-onset Staphylococcus aureus infections in pediatric patients: an experience at a Children's Hospital in central Illinois.

BACKGROUND: The nation-wide concern over methicillin-resistant Staphylococcus aureus (MRSA) has prompted many clinicians to use vancomycin when approaching patients with suspected staphylococcal infections. We sought to characterize the epidemiology of community-onset S. aureus infections in hospitalized children to assist local clinicians in providing appropriate empiric antimicrobial therapy. METHODS: From January 2005-June 2008, children (0-18 years old) admitted to the Children's Hospital of Illinois with community-onset S. aureus infections were identified by a computer-assisted laboratory-based surveillance and medical record review. RESULTS: Of 199 patients, 67 (34%) had invasive infections, and 132 (66%) had skin and soft tissue infections (SSTIs). Among patients with invasive infections, S. aureus isolates were more likely to be susceptible to methicillin (MSSA 63% vs. MRSA 37%), whereas patients with SSTIs, S. aureus isolates were more likely to be resistant to methicillin (MRSA 64% vs. MSSA 36%). Bacteremia and musculoskeletal infections were the most common invasive infections in both groups of S. aureus. Pneumonia with empyema was more likely to be caused by MRSA (P = 0.02). The majority (approximately 90%) of MRSA isolates were non-multidrug resistant, even in the presence of healthcare-associated risk factors. CONCLUSION: Epidemiological data at the local level is important for antimicrobial decision-making. MSSA remains an important pathogen causing invasive community-onset S. aureus infections among hospitalized children. In our hospital, nafcillin in combination with vancomycin is recommended empiric therapy in critically ill patients with suspected invasive staphylococcal infections. Because up to 25% of MSSA circulating in our area are clindamycin-resistant, clindamycin should be used cautiously as empiric monotherapy in patients with suspected invasive staphylococcal infections.