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.

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.

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

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.

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.

Infección invasiva por «Staphylococcus aureus» resistente a meticilina de origen comunitario en pacientes pediátricos sanos / Invasive infection caused by community acquired methicillin resistant Staphylococcus aureus on healthy pediatric patients

Staphylococcus aureus resistente a meticilina de adquisición comunitaria (SARM-AC) es una bacteria implicada en infecciones de diversa gravedad y localización. En este trabajo exponemos la actualidad de las infecciones por SARM-AC en pediatría, y lo ilustramos con dos ejemplos de infección virulenta en pacientes pediátricos sanos. El primer caso corresponde a una paciente con artritis séptica y neumonía necrosante por SARM-AC, y el segundo a un lactante con pleuroneumonía por SARM-AC. Ambos casos son un claro ejemplo de la relevancia de esta infección emergente en pediatría (AU)

The community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) is a bacterium that is frequently involved in severe infections and various locations. In this article we describe the actual state of CA-MRSA infections in pediatrics, and we illustrate it with two examples of virulent infection in healthy pediatric patients. The first case is in a patient with septic arthritis and necrotizing pneumonia caused by CA-MRSA, and the second one is in an unweaned baby with pleuropneumonia caused by CA-MRSA. Both cases are a clear example of the importance of this emerging infection in pediatrics (AU)

Antibióticos sin receta, ¿hasta cuándo? / Antibiotics without prescription. Until when?

No disponible

No disponible

[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.

Toxicity of antibiotics and antifungals on cultured human corneal cells: effect of mixing, exposure and concentration.

Toxic effects of topical drugs may be masked by manifestations of the disease they cure. The toxicity of drug mixtures has not been thoroughly studied. We therefore investigated cytopathic effects on primary cultures of human corneal cells of six topical antimicrobials singly and in combinations of any two, to determine the combined toxicity ranking and the interaction between duration of exposure and concentration. Preconfluent cultures were exposed to fixed dilutions of single drugs, or to equal-dilution mixtures of two drugs, for 7 and 14 days. Diminishing concentrations of single drugs were applied sequentially to cultures for 14 days. The number of metabolically competent cells was assessed by measuring hexosaminidase and total protein. Toxic effects depended on substance, concentration and exposure. The scale of toxicity determined for single drugs after 7 days of exposure was: gentamicin > econazole > or = methicillin > or = clotrimazole > or = miconazole > or = chloramphenicol. After 14 days this order changed: in particular chloramphenicol showed a highly increased toxicity. The order of diminishing effects was: gentamicin > chloramphenicol > or = methicillin > miconazole > econazole > clotrimazole. A clear reduction in cytopathic effects was observed when drug concentration was decreased progressively only in cultures treated with gentamicin or methicillin. All drug combinations were more toxic than their components at equal dilution. Combinations containing chloramphenicol ranked most toxic overall, those containing econazole least. A tapering off combination regime did not improve cell survival. These in vitro toxicity data complement clinical studies and suggest ways in which topical drugs can be chosen to minimise toxic effects to corneal surface.

Slowing of the heart during anaphylactic shock. A report of five cases.

Five patients are reported with anaphylactic shock reactions due to i.v. administration of atracurium, methicillin, amidotrezoate (n = 2) and plasma. In these patients a fall in heart rate (HR) from 5-50 beats.min-1 was recorded during the hypotensive period. In three of the patients HR was 40 beats.min-1 or less, and in two of the patients a hypotensive bradycardiac episode spontaneously reappeared after normal HR and BP were established. Central venous pressure (CVP) fell in one patient from 0.8 to 0.6 kPa as HR and BP decreased while arterial oxygen tension remained normal. All patients were in a stable condition after treatment with volume expansion and sympathomimetic drugs. These observations indicate that anaphylactic shock is associated with a strong and sometimes persistent vagal tone to the heart in parallel with the early reaction to hypotensive hypovolaemic shock.

[Interstitial nephropathies induced by meticillin: demonstration of distal tubule functional anomalies]. / Néphropathies interstitielles provoquées par la méticilline: mise en évidence d'anomalies fonctionnelles tubulaires distales.

Renal tubular dysfunction was investigated in two patients with meticillin-induced interstitial nephritis. Some degree of renal failure persisted after the acute episode in both cases. The first patient was investigated 10 weeks after the onset of the nephropathy. Nephrogenic diabetes insipidus and distal tubular acidosis were demonstrated. The second patient was investigated 7 months after the onset of the nephropathy. A major impairment in urinary concentration ability was demonstrated. Neither patient had proximal tubular dysfunction. These data show that meticillin-induced interstitial nephritis may be responsible for distal tubular abnormalities, namely nephrogenic diabetes insipidus and distal tubular acidosis, which may persist long after the onset of the nephropathy.

Antibiotic prophylaxis in vascular reconstructive surgery: a double-blind placebo-controlled study.

In a prospective randomized double-blind study of 141 patients referred for reconstructive vascular surgery on the abdominal aorta and the lower extremities, placebo was compared to antibiotic prophylaxis. The prophylaxis group received three doses of a combination of methicillin, 2 g and netilmicin, 200 mg. Antibiotic prophylaxis reduced postoperative wound infections as compared to placebo, i.e. 4/69 (5.8%) vs. 12/72, (16.7%) respectively (P = 0.04). No graft infections occurred. Two cases of postoperative septicaemia were seen in the placebo group, none in the antibiotic group. Among different procedures aortic-femoral bypass operations showed the highest wound infection rates. The two treatment groups were comparable with regard to all other postoperative complications registered, including nephro- and ototoxicity. The antibiotic regimen was considered safe, but had only marginal value as prophylaxis in vascular reconstructive surgery on the abdominal aorta and the lower extremities.

Methicillin-induced neutropenia.

During a 14-month period 68 patients were treated with methicillin for presumed or proved staphylococcal infection. Neutropenia, defined as a total neutrophil count less than 1500/cu mm3, developed in 23 patients (35%). Eosinophilia (eosinophil count more than 700/mm3) developed in 27 patients (40%), including 11 of the neutropenic patients. The epinephrine stimulation test in five patients resulted in a mean increase of 70% in the number of circulating neutrophils while the hydrocortisone stimulation test led to a mean increase of 800 neutrophils/mm3. Bone marrow examination in six patients showed maturation delay of the myeloid series. Neutropenia resolved within 3 to 7 days of discontinuation of methicillin therapy in all patients.