Safety and Efficacy of Ceftriaxone in the Treatment of Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections: A Noninferiority Retrospective Cohort Study.

BACKGROUND: Antistaphylococcal penicillins and cefazolin are the treatments of choice for methicillin-susceptible Staphylococcus aureus (MSSA) infections, requiring multiple doses daily. At Parkland, eligible uninsured patients with MSSA bloodstream infections (BSI) receive self-administered outpatient parenteral antimicrobial therapy (S-OPAT). Ceftriaxone was used in a cohort of S-OPAT patients for ease of once-daily dosing. OBJECTIVE: A retrospective study was conducted to evaluate clinical outcomes for patients discharged with ceftriaxone versus cefazolin to treat MSSA BSI. METHODS: A retrospective cohort noninferiority study design was used to assess treatment efficacy of ceftriaxone versus cefazolin among Parkland S-OPAT patients treated from April 2012 to March 2020. Demographic, clinical, and treatment-related adverse events data were collected. Clinical outcomes included treatment failure as defined by repeat positive blood culture or retreatment within 6 months, all-cause 30-day readmission rates, and central line-associated bloodstream infection (CLABSI) rates. RESULTS: Of 368 S-OPAT patients with MSSA BSI, 286 (77.7%) received cefazolin, and 82 (22.3%) received ceftriaxone. Demographics and comorbidities were similar for both groups. There were no treatment failures in the ceftriaxone group compared with 4 (1%) in the cefazolin group (P = 0.58). No difference in 30-day readmission rate between groups was found. The CLABSI rates were lower in ceftriaxone group (2%) compared with cefazolin (11%; P = 0.02). Limitations include retrospective cohort design. CONCLUSIONS: Ceftriaxone was found to be noninferior to cefazolin in this study. Our findings suggest that ceftriaxone is a safe and effective treatment of MSSA BSI secondary to osteoarticular or skin and soft tissue infections when used in the S-OPAT setting. POSTER ABSTRACT: OFID on 2018 Nov; 5(Suppl 1): S316: doi: 10.1093/ofid/ofy210.894.

A comparative genomic analysis between methicillin-resistant Staphylococcus aureus strains of hospital acquired and community infections in Yunnan province of China.

BACKGROUND: Currently, Staphylococcus aureus is one of the most important pathogens worldwide, especially for methicillin-resistant S. aureus (MRSA) infection. However, few reports referred to patients' MRSA infections in Yunnan province, southwest China. METHODS: In this study, we selected representative MRSA strains from patients' systemic surveillance in Yunnan province of China, performed the genomic sequencing and compared their features, together with some food derived strains. RESULTS: Among sixty selective isolates, forty strains were isolated from patients, and twenty isolated from food. Among the patients' strains, sixteen were recognized as community-acquired (CA), compared with 24 for hospital-acquired (HA). ST6-t701, ST59-t437 and ST239-t030 were the three major genotype profiles. ST6-t701 was predominated in food strains, while ST59-t437 and ST239-t030 were the primary clones in patients. The clinical features between CA and HA-MRSA of patients were statistical different. Compared the antibiotic resistant results between patients and food indicated that higher antibiotic resistant rates were found in patients' strains. Totally, the average genome sizes of 60 isolates were 2.79 ± 0.05 Mbp, with GC content 33% and 84.50 ± 0.20% of coding rate. The core genomes of these isolates were 1593 genes. Phylogenetic analysis based on pan-genome and SNP of strains showed that five clustering groups were generated. Clustering ST239-t030 contained all the HA-MRSA cases in this study; clustering ST6-t701 referred to food and CA-MRSA infections in community; clustering ST59-t437 showed the heterogeneity for provoking different clinical diseases in both community and hospital. Phylogenetic tree, incorporating 24 isolates from different regions, indicated ST239-t030 strains in this study were more closely related to T0131 isolate from Tianjin, China, belonged to 'Turkish clade' from Eastern Europe; two groups of ST59-t437 clones of MRSA in Yunnan province were generated, belonged to the 'Asian-Pacific' clone (AP) and 'Taiwan' clone (TW) respectively. CONCLUSIONS: ST239-t030, ST59-t437 and ST6-t701 were the three major MRSA clones in Yunnan province of China. ST239-t030 clonal Yunnan isolates demonstrated the local endemic of clone establishment for a number of years, whereas ST59-t437 strains revealed the multi-origins of this clone. In general, genomic study on epidemic clones of MRSA in southwest China provided the features and evolution of this pathogen.

Vancomycin AUC24 /MIC Ratio in Patients with Methicillin-Resistant Staphylococcus aureus Pneumonia.

BACKGROUND: Vancomycin is the treatment of choice for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. The area under the concentration-time curve from 0 to 24 hr (AUC24 )/minimum inhibitory concentration (MIC) ratio was recently introduced as a parameter for assessing clinical outcome by S. aureus. This study was purposed to apply the vancomycin AUC24 /MIC in patients with MRSA pneumonia. METHODS: Forty-seven patients with confirmed lower respiratory infection caused by MRSA during 2011 were enrolled. All patients were treated with vancomycin. Clinical characteristics and laboratory data were collected. AUC24 /MIC values were calculated as previously reported and patients were divided into two groups based on the bacteriologic response, which was eradicated or not, and an AUC24 /MIC value (above or below 400). RESULTS: MRSA infections were eradicated in 39 patients but 8 patients had persistent MSRA infection in the following cultures. The mean AUC24 /MIC values and vancomycin concentrations were not statistically different between patients with and without MRSA eradication. All 13 patients with a vancomycin MIC of 2 mg/L had an AUC24 /MIC below 400. CONCLUSION: AUC24 /MIC might not be a reliable indicator for assessing treatment response of vancomycin in MRSA pneumonia. Relationship between vancomycin AUC24 /MIC and therapeutic outcome needs to undergo further studies, including sufficiently large sample size.

Prevalence and characteristics of Livestock-Associated Methicillin-Resistant Staphylococcus aureus (LA-MRSA) isolated from chicken meat in the province of Quebec, Canada.

This study was conducted to estimate the prevalence of Livestock-Associated Methicillin-Resistant Staphylococcus aureus (LA-MRSA) in retail chicken meat and broiler chickens from the Province of Quebec, Canada, and to characterize LA-MRSA isolates. A total of 309 chicken drumsticks and thighs were randomly selected in 2013 from 43 retail stores in the Monteregie. In addition, nasal swabs and caeca samples were collected in 2013-2014 from 200 broiler chickens of 38 different flocks. LA-MRSA was not detected in broiler chickens. Fifteen LA-MRSA isolates were recovered from four (1.3%) of the 309 chicken meat samples. Multi-Locus Sequence Typing (MLST) and SCCmec typing revealed two profiles (ST398-MRSA-V and ST8-MRSA-IVa), which were distinct using pulse-field gel electrophoresis (PFGE) and microarray (antimicrobial resistance and virulence genes) analyses. In addition to beta-lactam resistance, tetracycline and spectinomycin resistance was detected in all isolates from the 3 positive samples of the ST398 profile. Southern blot hybridization revealed that the resistance genes aad(D) and lnu(A), encoding resistances to aminoglycosides and lincosamides respectively, were located on plasmid. All isolates were able to produce biofilms, but biofilm production was not correlated with hld gene expression. Our results show the presence of two separate lineages of MRSA in retail chicken meat in Quebec, one of which is likely of human origin.

The Impact of Reporting a Prior Penicillin Allergy on the Treatment of Methicillin-Sensitive Staphylococcus aureus Bacteremia.

BACKGROUND: Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a morbid infection with mortality benefit from receipt of parenteral ß-lactam therapy. A substantial portion of MSSA bacteremia patients report penicillin allergy, but infrequently have true allergy. OBJECTIVE: To determine the frequency and predictors of optimal and adequate therapy in patients with MSSA bacteremia. DESIGN: Retrospective cohort. PARTICIPANTS: Adult inpatients with MSSA bacteremia, January 2009 through October 2013. MAIN MEASURES: The primary measure was a trial of optimal therapy (OT), defined as ≥3 inpatient days or discharge on any first-line agents (nafcillin, oxacillin, cefazolin, or penicillin G, if susceptible). The secondary measure was completion of adequate therapy (AT), defined as ≥10 inpatient days or discharge on an agent appropriate for MSSA bacteremia. Data were electronically gathered with key variables manually validated through chart review. Log-binomial regression models were used to determine the frequency and predictors of outcomes. KEY RESULTS: Of 456 patients, 346 (76%) received a trial of OT. Patients reporting penicillin allergy (13%) were less likely to receive OT trial than those without penicillin allergy (47% vs. 80%, p <0.001). Adjusting for other factors, penicillin allergy was the largest negative predictor of OT trial (RR 0.64 [0.49, 0.83]). Infectious Disease (ID) consultation was the largest positive predictor of OT trial across all patients (RR 1.34 [1.14, 1.57]). Allergy/Immunology consultation was the single most important predictor of OT trial among patients reporting penicillin allergy (RR 2.33 [1.44, 3.77]). Of 440 patients, 391 (89%) completed AT, with ID consultation the largest positive predictor of the outcome (RR 1.28 [1.15, 1.43]). CONCLUSIONS: Nearly 25% of patients with MSSA bacteremia did not receive OT trial and about 10% did not receive AT completion. Reported penicillin allergy reduced, and ID consult increased, the likelihood of OT. Allergy evaluation, coupled with ID consultation, may improve outcomes in MSSA bacteremic patients.

Adverse reactions to methicillin and nafcillin during treatment of serious Staphylococcus aureaus infections.

Relative toxicities of methicillin and nafcillin were compared in 70 patients with serious infections caused by Staphylococcus aureus. Of the 29 patients treated with nafcillin, four had fever, rash, and leukopenia and 1 had absolute neutropenia. Of the 41 patients treated with methicillin, 16 experienced 27 reactions. In addition to fever and skin rash, neutropenia and urinary tract abnormalities were common. Methicillin and nafcillin are equally effective in treating S aureus infections, but methicillin was significantly and more frequently associated with adverse drug reaction that was nafcillin.

Nephropathy associated with methicillin therapy. Prevalence and determinants in patients with staphylococcal bacteremia.

The nephropathy associated with methicillin sodium therapy is considered to be rare, but its prevalence is unknown. We reviewed the antibiotic therapy of 81 cases of Staphylococcus aureus bacteremia to establish the frequency and determinants of methicillin nephropathy in that disease. Fifty-two patients received methicillin; nine (17%) experienced the characteristic clinical signs previously associated with drug-induced acute interstitial nephritis. This nephropathy uniformly subsided after methicillin was withdrawn, and did not always include deterioration of renal function. Factors that correlated with methicillin nephropathy were endocarditis and prolonged treatment, but not intravenous drug abuse. There was only one adverse reaction among 29 patients treated with a cephalosporin. It was similar to the nephropathic reactions to methicillin. Thus, reversible renal abnormalities are prevalent during methicillin therapy, particularly among patients with staphylococcal infections such as endocarditis. When prolonged therapy with methicillin is required, the urinary sediment and renal excretory function should be monitored.

Staphylococcal endocarditis in drug users. Clinical and microbiologic aspects.

Forty patients had staphylococcal endocarditis and a history of parenteral drug abuse. Clinical and microbiologic features of their cases were evaluated. None of our patients were known to have had preexisting valvular disease. The tricuspid valve lesions and their pulmonary complications were the predominant findings. Systemic complications in the form of meningitis, glomerulonephritis, empyema, arthritis, and nosocomial Gram-negative septicemia occurred in 33% of our patients. Of interest was the high incidence of reactions to therapy especially with methicillin sodium, which occurred in 30% of patients. Correlation of phage type and group with the antibiotic sensitivities of individual staphylococci showed that group 3 and phage types 6, 42E, 54, and 75 were much more resistant to penicillin than other groups and types. The clinical outcome did not relate to phage type and group or to antibiotic sensitivity of the organism.

Acute interstitial nephritis due to methicillin.

Fourteen patients are described with a syndrome of methicillin-induced interstitial nephritis. In all patients severe renal dysfunction developed with an average peak serum creatinine of 8 mg/100 ml. An increased total peripheral eosinophil count was found in all patients. All patients had sterile pyuria and each of nine patients studied by Wright's stain of urine sediment had marked eosinophiluria. These findings are suggestive of methicillin-induced interstitial nephritis, although proteinura was a variable finding in our patients. Eight of 14 patients in our study received prednisone therapy for their interstitial nephritis, and the time lapse between maximal and final base line serum creatinine levels was statistically less in the prednisone-treated compared to the nontreated groups. Clinical manifestations of this syndrome are discussed, and the light and electron microscopic and immunofluorescent findings on renal biospy are described.

Sodium wasting, acidosis and hyperkalemia induced by methicillin interstitial nephritis. Evidence for selective distal tubular dysfunction.

A 61 year old male patient was studied who manifested dehydration, azotemia, acidosis and hyperkalemia six weeks after exposure to methicillin. Thyroid and adrenal glucocorticoid and mineralocorticoid function were normal. The dehydration was found to be caused by a profound sodium-losing nephropathy; urinary sodium ranged from 78 to 101 meq/day during a salt restricted diet. A distal renal tubular acidosis and a quantitively impaired ability to excrete potassium were also found. These defects were relatively unresponsive to mineralocorticoid or prednisone therapy. A renal biopsy specimen showed an interstitial nephritis which selectively affected distal tubules and was thought to be secondary to methicillin. The data suggest functional impairment specific for the distal tubule, but with only a modest decrease in the glomerular filtration rate.

A ten-year assessment of methicillin-associated side effects.

The exact incidence and importance of side effects associated with methicillin therapy in children is unknown. During the ten-year period from 1964 to 1974 approximately 3,000 Houston children who received methicillin were observed for side effects. The great majority of these patients received the drug for less than ten days; however, side effects were more common in patients receiving long-term therapy. In order to assess these side effects, experiences with 124 children who received methicillin for ten days or longer were reviewed in depth. The average dose of methicillin was 200 mg/kg/day and the average duration was 22 days. In this highly selected group there were no adverse side effects in 54.8% and only eosinophilia in an additional 13%. Leukopenia occurred in 16%, microscopic hematuria in 8%, gross hematuria in 4%, skin rash in 6%, and "drug fever" in 6%. In many instances several of these side effects occurred within a single patient so that the total number of patients with definite side effects was 39 of 124 (31.5%). The true incidence figure of overall side effects is much lower than 31.5%. Corrected incidence rates based on a conservative figure of 3,000 methicillin-treated children are less than 1.5% for all side effects. In some patients the mechanism producing the adverse reactions seemed to be chemical irritation or toxicity and in others hypersensitivity. In nine of the 39 patients follow-up studies were not optimal. In the other 30 patients all side effects were reversible.

Interstitial nephritis caused by methicillin. Studies in a case complicating staphylococcal sepsis with acute glomerulonephritis.

A 16-year-old student was admitted with acute, oliguric renal failure complicating staphylococcal sepsis. During treatment with methicillin drug hypersensitivity was suspected, and antibiotic was changed to vancomycin; by day 19 hemodialysis was discontinued. Renal biopsy showed two pathologic processes: acute exudative glomerulonephritis and widespread tubulointerstitial nephritis. In addition to glomerular immunoglobulin and C'3 deposits, interstitial and focal tubular basement membrane deposits of IgG were seen. Antiserum to DPO (methicillin) haptens localized apparently to the same tubular sites, as did fluorescein-conjugated antibodies from the patient's serum. The data suggest that interstitial nephritis was caused by serum antibodies to methicillin which bound to sites in renal tubules to which methicillin also had fixed. The acute tubulointerstitial nephritis complicated acute oliguric glomerulonephritis of staphylococcal sepsis.

Death from pseudomembranous enterocolitis.

During the past 2 years at the Los Angeles County-University of Southern California Medical Center (LAC-USC), there have been 2 deaths from pseudomembranous enterocolitis. Each of these deaths occurred postoperatively in previously healthy women who received pronlonged antibiotic prophylasix. The implications of these poor therapeutic results are discussed. The distinctive clinical symptology of a patient with pseudomembranous enterocolitis is described, and current treatment recommendiations are presented.

[Antibiotic-induced hemorrhagic cystitis]. / Antibiotikaudløst haemoragisk cystitis.

Two cases of haemorrhagic cystitis following treatment with methicillin and penicillin G are presented. Two males, aged 24 and 45 years, presented identical symptoms including haematuria, dysuria and pollakisuria. The condition has in rare instances been described as caused by antibiotic treatment; in all cases a penicillin was involved. All symptoms promptly vanished when the antibiotic treatment was stopped, and the reactions were possibly allergic since cross-reactions between different penicillins have been described in earlier cases.

Interaction study between vancomycin and liposomes containing natural compounds against methicillin-resistant Staphylococcus aureus clinical isolates

ABSTRACT The treatment of infections caused by resistant microorganisms is limited, and vancomycin (VAN) treatment failures for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia are not uncommon, even when MRSA clinical isolates are susceptible to VAN. Thus, this study proposed the association of VAN with usnic acid and ß-lapachone encapsulated into liposomes as a novel therapeutic option for infections caused by MRSA. Liposomes containing ß-lap (ß-lap-lipo) or usnic acid (UA-lipo) were prepared by the thin lipid film hydration method followed by sonication. Antimicrobial activity against MRSA clinical isolates was investigated by the microdilution method according to the Clinical and Laboratory Standards Institute (CLSI). The interaction studies were carried out using the checkerboard method and epsilometer test (Etest). The interaction between VAN and ß-lap or ß-lap-lipo was synergistic (FICI = 0.453 and FICI = 0.358, respectively). An additive interaction between VAN and UA (FICI = 0.515) was found. UA-lipo resulted in synergism with VAN (FICI = 0.276). The Etest reproduced the results obtained by the checkerboard method for approximately 82% of the analysis. Thus, the present study demonstrated that VAN in combination with UA-lipo, ß-lap or ß-lap-lipo synergistically enhanced antibacterial activity against MRSA