Methicillin-resistant Staphylococcal Infections Research Articles

The Home Environment Is a Reservoir for Methicillin-Resistant Coagulase-Negative Staphylococci and Mammaliicocci.

Coagulase-negative staphylococci (CoNS) and mammaliicocci are opportunistic human and animal pathogens, often resistant to multiple antimicrobials, including methicillin. Methicillin-resistant CoNS (MRCoNS) have traditionally been linked to hospitals and healthcare facilities, where they are significant contributors to nosocomial infections. However, screenings of non-hospital environments have linked MRCoNS and methicillin-resistant mammaliicocci (MRM) to other ecological niches. The aim of this study was to explore the home environment as a reservoir for MRCoNS and MRM. A total of 33 households, including households with a dog with a methicillin-resistant staphylococcal infection, households with healthy dogs or cats and households without pets, were screened for MRCoNS and MRM by sampling one human, one pet (if present) and the environment. Samples were analyzed by a selective culture-based method, and bacterial species were identified by MALDI-TOF MS and tested for antibiotic susceptibility by the agar disk diffusion method. Following whole-genome sequencing, a large diversity of SCCmec elements and sequence types was revealed, which did not indicate any clonal dissemination of specific strains. Virulome and mobilome analyses indicated a high degree of species specificity. Altogether, this study documents that the home environment is a reservoir for a variety of MRCoNS and MRM regardless of the type of household.

A Web-Based Dynamic Nomogram to Predict the Risk of Methicillin-Resistant Staphylococcal Infection in Patients with Pneumonia.

The aim of this study was to create a dynamic web-based tool to predict the risks of methicillin-resistant Staphylococcus spp. (MRS) infection in patients with pneumonia. We conducted an observational study of patients with pneumonia at Cho Ray Hospital from March 2021 to March 2023. The Bayesian model averaging method and stepwise selection were applied to identify different sets of independent predictors. The final model was internally validated using the bootstrap method. We used receiver operator characteristic (ROC) curve, calibration, and decision curve analyses to assess the nomogram model's predictive performance. Based on the American Thoracic Society, British Thoracic Society recommendations, and our data, we developed a model with significant risk factors, including tracheostomies or endotracheal tubes, skin infections, pleural effusions, and pneumatoceles, and used 0.3 as the optimal cut-off point. ROC curve analysis indicated an area under the curve of 0.7 (0.63-0.77) in the dataset and 0.71 (0.64-0.78) in 1000 bootstrap samples, with sensitivities of 92.39% and 91.11%, respectively. Calibration analysis demonstrated good agreement between the observed and predicted probability curves. When the threshold is above 0.3, we recommend empiric antibiotic therapy for MRS. The web-based dynamic interface also makes our model easier to use.

Population Pharmacokinetic and Pharmacodynamic Analysis for Maximizing the Effectiveness of Ceftobiprole in the Treatment of Severe Methicillin-Resistant Staphylococcal Infections.

Ceftobiprole is a fifth-generation cephalosporin used for different Gram-positive bacterial infections. A population pharmacokinetic analysis was conducted in real-life clinical patients to assess the adequacy of current dosages. Population pharmacokinetics was conducted using non-linear mixed effect modeling. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) of free trough or steady-state concentration over MIC (fCtrough/MIC or fCss/MIC) ≥ 1 or ≥4 associated with both the standard and intensified dosing regimens adjusted for renal function. Cumulative fraction of response (CFR) against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) were also calculated. A total of 132 patients with 503 concentrations were included. Most of them (107/132, 81.1%) had hospital- or community-acquired pneumonia, endocarditis, and bacteremia. A three-compartment model adequately fitted ceftobiprole concentration-time data. Estimated glomerular filtration rate significantly affected drug clearance. Monte Carlo simulations showed that the optimal target of fCtrough/MIC or fCss/MIC ≥ 4 is achieved only with the use of the standard dosages administered by continuous infusion (CI) against MRSA infections in patients with preserved renal function. Intensified dosages administered by CI are needed in patients with impaired renal function and/or augmented renal clearance against MRSA and in patients with preserved renal functions against MRSE.

Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus among Patients Diagnosed with Surgical Site Infection at Four Hospitals in Ethiopia.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of severe surgical site infections (SSI). The molecular epidemiology of MRSA is poorly documented in Ethiopia. This study is designed to determine the prevalence of MRSA and associated factors among patients diagnosed with SSI. A multicenter study was conducted at four hospitals in Ethiopia. A wound culture was performed among 752 SSI patients. This study isolated S. aureus and identified MRSA using standard bacteriology, Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS), and cefoxitin disk diffusion test. The genes mecA, femA, vanA, and vanB were detected through PCR tests. S. aureus was identified in 21.6% of participants, with 24.5% of these being methicillin-resistant Staphylococci and 0.6% showing vancomycin resistance. Using MALDI-TOF MS for the 40 methicillin-resistant Staphylococci, we confirmed that 31 (77.5%) were S. aureus, 6 (15%) were Mammaliicoccus sciuri, and the other 3 (2.5%) were Staphylococcus warneri, Staphylococcus epidermidis, and Staphylococcus haemolyticus. The gene mecA was detected from 27.5% (11/40) of Staphylococci through PCR. Only 36.4% (4/11) were detected in S. aureus, and no vanA or vanB genes were identified. Out of 11 mecA-gene-positive Staphylococci, 8 (72.7%) were detected in Debre Tabor Comprehensive Specialized Hospital. Methicillin-resistant staphylococcal infections were associated with the following risk factors: age ≥ 61 years, prolonged duration of hospital stay, and history of previous antibiotic use, p-values < 0.05. Hospitals should strengthen infection prevention and control strategies and start antimicrobial stewardship programs.

Intensive care unit presentation of central corneal descemetocele secondary to Methicillin-Resistant staphylococcal infection superimposed by a hypopyon: a case report.

This report presents the first instance of a methicillin-resistant Staphylococcus aureus descemetocele presentation in a 51-year-old African American male, with co-presenting hypopyon sequelae successfully managed conservatively in an intensive care unit setting. An instance of a methicillin-resistant Staphylococcus aureus has not yet been documented in the literature. Likewise, a co-presentation with a hypopyon, which is known as a formation of inflammatory debris rich in white blood cells has not been studied. The presence of a hypopyon in the instances of bacterial descemetocele herniation should be further evaluated to see if there are associations with conservative, nonsurgical intervention outcomes.

Evaluation of vancomycin individualized model-based dosing approach in neonates.

Vancomycin is commonly used to treat methicillin-resistant staphylococcal infections in neonates. Consensus on its ideal dosing in neonates has not been achieved. Model-based dosing recently has evolved as an important tool to optimize vancomycin initial dosing. The aim of this is to evaluate a population pharmacokinetic model-based approach in achieving the vancomycin therapeutic target of an AUC0-24 400 as recommended by the recent IDSA treatment guidelines. This model was implemented as a simple Excel calculator to individualize and optimize vancomycin initial dosing in neonates. An Excel calculator was developed using a previously published population pharmacokinetic model in neonates. It was evaluated using retrospectively retrieved data. For each patient, the initial empiric dose was calculated using the proposed Excel model and the most widely used neonatal dosing references. The probability of achieving the target AUC0-24 of >400mgh/L using the model-based method was calculated and compared with that of the empiric doses using other references. This analysis included 225 neonates. The probability of achieving the target AUC0-24 >400 was 89% using our model-based approach compared with 11%-59% using tertiary neonatal dosing references (p<0.01 for all comparisons). These innovative personalized dosing calculators are promising to improve vancomycin initial dosing in neonates and are easily applicable in routine practices.

Development of more potent anti-microbial drugs from extracts of five medicinal plants resistant to S. aureus in human fluids: an ex vivo and in vivo analysis

Methicillin-resistant staphylococcal infections are a serious public health concern worldwide, especially in our region, due to the unavailability of accurate therapeutics. The aim of this study was to determine the resistance pattern of Staphylococcus aureus isolated from clinical and asymptomatic specimens and to identify antimicrobial agents against methicillin resistant S. aureus strains. 47 samples (pus, urine, blood, nose and milk) together from diverse healthcare hospitals in Faisalabad for location of S. strains. Aureus by biochemical examination. The results of these biochemical tests showed that 21 of 47 samples were positive for S. aureus. A resistance study found that 10 of 21 S. aureus isolates were resistant to oxacillin. Twenty-five medicinal plants were collected from different parts of Saudi Arabia, air-dried and extracted with methanol. These plant extracts were then screened for potential against oxacillin-resistant S. aureus. In addition, the semi-maximum inhibitory concentration (IC50) of effective medicinal plant extracts was measured using the micro-dilution method. Methanol extracts from five plants (Centratherum antherminticum, Eucalyptus globulus, Lawsonia inermis, Punica granatum and Rubia cordifolia) have been shown to have anti-bacterial activity against clinically isolated S. oxacillin resistant strains. It was done. The IC50 for these methanol extracts of S. aureus ranged from 0.250 to 4.30 mg/mL. Our results suggest that various medicinal plants contain potential anti-bacterial agents against S. aureus, which may contribute to the development of more effective agents against multidrug resistant S. aureus infections. It might help.

SG-APSIC1088: Two-stage primary total knee arthroplasty for evolutive infected arthritis with coexistent joint destruction

Objectives: The treatment of infected knee arthritis in patients with coexisting joint destruction, including superimposed advanced arthritis or chronic osteomyelitis, is challenging. We investigated the outcomes of 2-stage primary total knee arthroplasty (TKA) for evolutive infected arthritis with coexistent joint destruction. Methods: We retrospectively reviewed the cases of 50 patients from 5 hospitals who presented with infected arthritis of the knee and were treated with 2-stage TKA: debridement and antibiotic-loaded articulating cement spacer (ALCS) insertion as the first stage and TKA as the second stage. We recorded demographics, laboratory results, and radiographic findings including Kellgren-Lawrence classification (KL) for knee arthritis. Outcomes including infection eradication, knee range of motion (ROM), and patient-reported outcome measures were evaluated. Results: The patient cohort had a mean age of 71.8 years (range, 40–86); they were followed for an average of 4.1 years (range, 2.2–13.3). Also, 40 patients showed KL grade 4, whereas 10 patients showed grade 3. A pathogen was identified in 38 cases (73.1%); methicillin-resistant staphylococci infections (N = 16) and Candida spp infections (N = 7) were the 2 most common types. Constrained prostheses were used in 10 cases (20%). Stem augmentations were used in 15 cases (36.0%) and block augmentations were used in 8 cases (19.0%). One patient had recurrent infection after TKA, so the eradication rate was 98%. After 2-stage TKA, the mean knee ROM was 119.4° (range, 80°–140°) and the mean Knee Society (KS) knee score was 90.4, the average KS function score was 84.7, the average Hospital for Special Surgery (HSS) score was 87.2, and the average Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was 16.7. The KS function scores (P = .029) and the WOMAC scores (P = .022) were significantly better in 17 patients who underwent ALCS insertion within 30 days of infection diagnosis compared to the other 33 patients. Conclusions: The 2-stage primary TKA for patients with infected knee arthritis with coexisting joint destruction showed satisfactory outcomes with a low infection recurrence. However, constrained prostheses or augmentation use may be necessary. Notably, some functional scores were better in the group that underwent ALCS insertion relatively early after the infection diagnosis.

Continuous Vancomycin Infusion versus Intermittent Infusion in Critically Ill Patients.

Vancomycin is the best-choice medication for methicillin-resistant staphylococcal and enterococcal infections, which are major problems in intensive care units (ICUs). Intermittent infusion is standard for vancomycin, although delayed therapeutic target achievement and supra- and subtherapeutic levels are concerns. A recently proposed alternative with superior therapeutic target achievement is continuous infusion. To compare the benefits of continuous (CVI) and intermittent (IVI) vancomycin infusion. This quasi-experimental study used propensity score-matched historical controls and adult patients in medical and surgical ICUs for whom vancomycin was indicated. The experimental group received CVI for ≥ 48 hours. Data on patients receiving IVI between January 2018 and October 2020 were reviewed. Capability to achieve serum vancomycin therapeutic targets (48 and 96 hours), episodes of supra- and subtherapeutic levels, treatment success, mortality, and incidence of acute kidney injury (AKI) were analyzed before and after one-to-two propensity score matching. The CVI group had 31 patients, while the unmatched IVI group had 125. More CVI patients achieved the therapeutic target within 48 hours (54.8% vs 25.6%; P=0.002). CVI patients had a higher median number of supratherapeutic episodes (2 vs 1; P=0.007) but a lower median for subtherapeutic episodes (0 vs 1; P=0.003). Other outcomes demonstrated no differences. After propensity score matching, target achievement within 48 hours (54.8% vs 22.6%; P=0.002) and fewer subtherapeutic episodes (0 vs 1; P=0.014) remained significant. CVI's rapid therapeutic target achievement and fewer subtherapeutic episodes make it superior to IVI. No differences in treatment success, mortality, or AKI are evident.

Evaluation and Susceptibility Pattern of Staphylococci Isolated From Clinical Specimens in POF Hospital, Wah Cantt.

Objective: To determine the frequency and antibiotic susceptibility pattern of Staphylococcus aureus and coagulase negative staphylococci isolated from clinical specimens as a result of culture and sensitivity.&#x0D; Materials &amp; Methods: This cross sectional study was carried out in POF Hospital Microbiology laboratory from January 2019 to September 2020. One hundred and eighty four staphylococci isolated from clinical specimens were processed as per standard methodology.&#x0D; Results: Out of 148, methicillin resistant S.aureus and methicillin resistant coagulase negative staphylococci were 38.04% and13.04% respectively. Infections caused by Methicillin resistant staphylococcal isolates were higher among the age group 31-40 years (71.4%, OR=2.68). Out of thirty expired patients, 53.3% had been infected with methicillin resistant staphylococcal infections. The methicillin resistant staphylococci were most frequent in miscellaneous category of clinical specimens (80.0%, OR=4.63). The susceptibility analysis revealed that methicillin resistant staphylococci are 100% resistant to penicillin, meropenem and amoxycillin-clavulanate (p=0.000). A significant association of methicillin resistance was also noticed against amikacin (p=0.002), ciprofloxacin (p=0.001), clindamycin (p=0.005) and erythromycin (p=0.000). Moxifloxacin, linezolid and vancomycin are the most effective choice for infections caused by methicillin resistant staphylococci.&#x0D; Conclusions: The methicillin-resistant staphylococci are highly resistant to commonly prescribed oral as well as injectable antibiotics. Establishment and implementation of infection control policies are required to combat the grave situation of increasing antibiotic resistance.

A comparsion study between debridement, antibiotics, and implant retention and two-stage revision total knee arthroplasty for the management of periprosthetic joint infection occurring within 12 weeks from index total knee arthroplasty

BackgroundManaging periprosthetic joint infections are variable in practices. Debridement, antibiotics, and implant retention (DAIR) is one of the favorable interventions. Given that the success rate of the two-stage revision total knee arthroplasty (rTKA) might be overestimated. The purpose of this study is to compare the success rate between DAIR and standard two-stage rTKA with a comparable intervention time.MethodsWe retrospectively reviewed the consecutive knee periprosthetic joint infection cases which underwent DAIR or two-stage rTKA (all procedures were performed by the senior author) within 12 weeks since their primary TKA between July 2009 and October 2019. Average follow-up was 72.20 ± 40.70 months (range 29–148 months) in the DAIR group compared to 89.14 ± 43.06 months after spacer insertion (range 29–163 months) in the two-stage revision group (P = 0.156). According to different interventions, demographic data; timing of surgical intervention; hospital for special surgery knee score; and success rate were collected and compared between the DAIR group and two-stage revision group. Failure of treatment was based on the Delphi consensus and the fate of spacers. The pathogen types and failure cases were also recorded and analyzed.ResultsAverage follow-up was 72.20 ± 40.70 months (range 29–148 months) in the DAIR group compared to 89.14 ± 43.06 months after spacer insertion (range 29–163 months) in the two-stage revision group. Time from index surgery was 3.90 ± 2.92 weeks (range 0–12 weeks) in the DAIR group, and 5.11 ± 2.86 weeks (range 0–12 weeks) in the 2-stage exchange group, respectively. The success rate was 70.0% and 75.0% in the DAIR group and two-stage revision group, respectively. But no significant differences were observed between the two groups.ConclusionDAIR demonstrated comparable effectiveness with two-stage rTKA. We recommended DAIR as a choice for patients with current infection within 12 weeks after primary TKA. For methicillin-resistant staphylococcal infections and fungal infections, two-stage rTKA might be preferred.

#77 Prevalence of Staphylococcus aureus bacteremia at Saint Damien Hospital, Nos Petits Frères et Sœurs January (HSD/NPFS) 2020-June 2021, Haiti

Abstract Background Staphylococcus Aureus (SA) is one of the main agents implicated in healthcare-associated infections (HAI) [1]. These infections are associated with significant morbidity and mortality, particularly methicillin-resistant staphylococcal (MRSA) infections, and their costs are also a concern. Bacteremia is regularly monitored at Saint Damien Hospital (HSD), for the year 2020 an increase in Staphylococcus aureus (SA) bacteremia was observed in certain units of the hospital. In this context, all SA infections were reviewed during eighteen months to determine the prevalence of methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) staphylococcus aureus infections, their origins: in healthcare-associated infections (HAI), community-acquired infections (CI) and the distribution of MRSA per unit Method A Descriptive retrospective study was carried out at Saint Damien Hospital from January 2020 to June 2021. It includes all hospitalized children under fourteen years old (14) who had a positive blood culture for SA per site, only the 1st blood culture was taken into account. According to NHSN/CDC, are defined as infections associated with healthcare-associated infections occurring at ≥ 72 hours of hospitalization (HAI) and as community-acquired infectious infections occurring at = &amp;lt; 48 hours of hospitalization.. Data were collected from microbiology laboratory registers and patient records Results From January 2020 to June 2021, two thousand two hundred thirty five 2235 blood cultures were performed. The positivity rate was 21.43% (n=479/2235) distributed in different units. 16.49% SA strains were isolated (n=79/479), including fifty (50) strains of MRSA (63.29%) and twenty nine (29) strains of MSSA (36.70%) (n=29/79).From the strains of MRSA, 54% (n=27/50) were HAI and 46% community infections (CI) (n=23/50). The Origin of the infections (HAI/CI) was not significantly associated with MRSA and MSSA strains (p=0.6235), MRSA mainly came from emergency 48% (n=24/50) followed by neonatology 20% (n=10/50), intensive care 10% (5/50) and oncology at 10% (5/50). (n=19/79), the mortality rate attributable to MRSA and MSSA was 28% (n=14/50) and 17.24% (n=5/29), respectively. 46% of MRSA were resistant to more than 3 families of antibiotics (n = 23/50). SA strains were resistant to gentamycin at 30.37% (n=24/79) to 54.34% to sulfametoxazole (n=43/79) and 18.98% and to vancomycin (n=15/79 Conclusion The frequency of SA infections, specifically MRSA, is of great concern. Its existence in the community and its multiresistance, in particular to vancomycin, is an alert making this bacteremia a priority at Saint Damien Hospital, the standard precautions measures, the proper use of antibiotics by clinicians and epidemiological surveillance local would be needed to help control its spread.

What is the appropriate extended duration of antibiotic prophylaxis after two-stage revision for chronic PJI?

AimsTo explore the effect of different durations of antibiotics after stage II reimplantation on the prognosis of two-stage revision for chronic periprosthetic joint infection (PJI).MethodsThis study involved a retrospective collection of patients who underwent two-stage revision for chronic PJI and continued to use extended antibiotic prophylaxis in two regional medical centres from January 2010 to June 2018. The patients were divided into a short (≤ one month) or a long (> one month) course of treatment based on the duration of antibiotics following stage II reimplantation. The difference in the infection control rate between the two groups was compared, and prognostic factors for recurrence were analyzed.ResultsA total of 105 patients with chronic PJI were enrolled: 64 patients in the short course group and 41 patients in the long course group. For 99 of the patients, the infection was under control during a follow-up period of at least 24 months after two-stage revision. For the short course group, the mean duration of antibiotic prophylaxis after stage II reimplantation was 20.17 days (SD 5.30) and the infection control rate was 95.3%; for the long course group these were 45.02 days (SD 15.03) and 92.7%, respectively. There was no significant difference in infection control rates between the two groups (p = 0.676). Cox regression analysis found that methicillin-resistant staphylococcus infection (p = 0.015) was an independent prognostic factor for recurrence.ConclusionAfter stage II reimplantation surgery of two-stage revision for chronic PJI, extended antibiotic prophylaxis for less than one month can achieve good infection control rate.Cite this article: Bone Joint Res 2021;10(12):790–796.

The SCCmec Types and Antimicrobial Resistance among Methicillin-Resistant Staphylococcus Species Isolated from Dogs with Superficial Pyoderma.

This study characterizes clinical methicillin-resistant staphylococcal (MRS) isolates obtained from superficial pyoderma infections in dogs. Our interest was to determine the staphylococcal cassette chromosome mec (SCCmec) type and the antimicrobial susceptibility among MRS isolates from clinical cases. Skin swabs were collected and cultured. Staphylococcus species were identified and characterized with biochemical tests and MALDI-TOF-MS and antimicrobial susceptibility testing by disk diffusion. mecA detection and staphylococcal cassette chromosome mec (SCCmec) typing were achieved by PCR. Of the 65 clinical samples, 56 (86.2%) staphylococcal infections were identified. Twelve (21%) of 56 isolates were MRS infections. All MRS isolates were multidrug resistant. The ccrC and class-C2 mec, which were SCCmec type V, were the most prevalent (66.7%) among the 12 MRS isolates. The predominant SCCmec type V was found in S. aureus, S. intermedius group, S. lentus, S. xylosus, and S. arlettae. Treatment failure is a concern with the emergence of highly resistant MRS in dogs associated with superficial pyoderma. The detection of type V SCCmec MRS has previously been reported among veterinarians and dog owners but not in Northern Thailand. These infections serve as a reminder to improve infection prevention and control measures including reducing environmental contamination and potential zoonotic exposures to MRS. In addition, educational awareness of these risks in small animal hospitals needs to be increased among veterinary hospital staff, clients, and patients.

Ceftaroline In-vitro Activity against Methicillin Resistant Staphylococcal Isolates in a Rural Tertiary Healthcare Centre

Introduction: The emergence of Methicillin Resistant (MR) staphylococcal infections had led to fewer therapeutic options. Ceftaroline fosamil is the only cephalosporin approved by United States of America (USA) Food and Drug Administration (FDA) till now which has activity against MR staphylococcal isolates. Until now, studies on in-vitro activity of ceftaroline are limited. Aim: To know the susceptibility pattern of Methicillin Resistant Staphylococcus aureus (MRSA) and Methicillin Resistant Coagulase Negative Staphylococci (MRCoNS) against ceftaroline in a rural tertiary health care centre. Materials and Methods: The present cross-sectional study was conducted in a tertiary care hospital in rural part of Karnataka between two months (July and August 2019). A total of 50 consecutive, non repetitive clinical isolates of MRSA and MRCoNS were obtained. Antibiotic susceptibility testing was done according to Clinical and Laboratory Standards Institute (CLSI) guidelines. The Minimum Inhibitory Concentration (MIC) of ceftaroline was detected using E-strips (Biomerieux). The CLSI breakpoints applied for the interpretation of ceftaroline MIC- Sensitive: ≤1 μg/mL; Susceptible Dose Dependent (SDD): 2-4 μg/ mL and resistant ≥8 μg/mL). Staphylococcus aureus American Type Culture Collection (ATCC) 29213 was used as a quality control. Statistical analysis was done using microsoft excel. Percentages were used in this study to analyse variables. Results: Out of 50 MR staphylococcal isolates, 10 (20%) were MRSA and 40 (80%) were MRCoNS. Of the MR staphylococcal isolates tested, 49 (98%) were sensitive to ceftaroline. The MIC 50 and MIC 90 for the 50 MR staphylococci was 0.25 μg/mL and 1 μg/mL, respectively. Conclusion: Ceftaroline demonstrated a potent in-vitro activity against MR staphylococci. So it can be used as an effective drug in the treatment of such infections.

New acridine derivatives as promising agents against methicillin-resistant staphylococci – From tests to in silico analysis

The present study describes the antibacterial activity of several new derivatives of tacrine or cyclopentaquinoline bound to either 6-hydrazinenicotinic acid or 4-fluorobenzoic acid through an aliphatic chain against methicillin-resistant staphylococcal strains. All derivatives showed antibacterial activity against all tested methicillin-resistant staphylococci. Of these, compounds 6, 18, 23 and 24 exhibited the highest activity, ranging from 4.87 to 19.5 μg/mL MBC (Minimum Bactericidal Concentration) depending on the bacterial strain. These values were not much greater than that for vancomycin, the reference standard for the treatment of methicillin-resistant Staphylococci infections in humans. In addition, all synthesized compounds underwent a quantitative structure-activity relationship analysis. Correlation and multicollinearity tests were used to select descriptors as independent variables for multiple linear regression models to quantify the relationships between biological activity and the structural parameters.

Minocycline Combined with Vancomycin for the Treatment of Methicillin-Resistant Coagulase-Negative Staphylococcal Prosthetic Joint Infection Managed with Exchange Arthroplasty.

Introduction: Treatment of methicillin-resistant (MR) staphylococcal prosthetic joint infections (PJIs) remains a matter of discussion, with vancomycin-rifampin combination therapy being the preferred treatment for DAIR and one-stage exchange arthroplasty strategies. This study analyzes the outcomes of patients with chronic methicillin-resistant coagulase-negative staphylococcal PJIs treated with vancomycin-minocycline combination therapy.Methods: This prospective, single center cohort study included all chronic MR coagulase-negative staphylococcal PJIs (01/2004-12/2014) treated with exchange arthroplasty and at least 4 weeks of minocycline-vancomycin. The following endpoints were considered: reinfection including relapse (same microorganism) and a new infection (different microorganism) and PJI-related deaths. Their outcomes were compared with PJIs treated with rifampin-vancomycin during the same period.Results: Thirty-four patients (median age, 69 years) with 22 hip and 12 knee arthroplasty infections were included. Sixteen (47%) had previously been managed in another center. Median vancomycin MIC of strains was 3 mg/L. Nineteen underwent one-stage, 15 two-stage exchange arthroplasty. After a median [IQR] follow-up of 43 [26-68] months, 2 patients relapsed and 6 developed a new PJI. Compared to 36 rifampin-vancomycin treated PJIs, relapse- or reinfection-free survival rates didn't differ, but more new infections developed in the minocycline group (6 vs 3; P 0.3).Conclusions: Minocycline-vancomycin combination therapy for chronic MR coagulase-negative staphylococcal PJIs seems to be an interesting therapeutic alternative.

Methicillin and Inducible Clindamycin-resistant Staphylococcus aureus Isolates from Clinical Samples in Abia State

Staphylococcus aureus is a major bacterial pathogen that causes different community and hospital-acquired infections. S. aureus resistant to methicillin has become a big and expanding problem of concern in many developing countries. Clindamycin has also been discovered to be a preferred therapeutic alternative for the treatment of both methicillin susceptible and resistant staphylococcal infections. This study examined the prevalence of Methicillin-resistant Staphylococcus aureus (MRSA) in clinical samples of patients in Abia state, Nigeria using standard recommended procedures. A total of 750 clinical specimens of blood and urine samples, wound, ear, nasal, high vaginal and ear swabs were collected from three major health facilities in Abia state, Nigeria. Each sample was cultured for bacterial isolates and examined for colonial and cellular morphology while biochemical identification was performed. Antimicrobial susceptibility test was performed on Mueller-Hinton agar (MHA) by disc diffusion method and MRSA screening was done using cefoxitin disc. A total of 265 (35.3%) S. aureus isolates were recovered, out of which 126(47.5%) were from males and 139(52.5%) were from females, however there was no association between the prevalence and gender (p-value = 0.05) and also prevalence and age (p-value = 0.52). Of the 265 S. aureus isolates recovered, 164(61.9%) were MRSA. All 100% of the MRSA were susceptible to vancomycin, 120(73.2%) to clindamycin, 92(56.1%) to gentamycin. All 100% were resistant to ceftazidine, 157(95.7%) to cloxacillin, 146(89.0%) to augmentin, 136(82.9%) to ceftriaxone and 103(61.6%) to erythromycin. The MRSA strains showed much higher resistance rate than their MSSA counterparts to all tested antibiotic except clindamycin. 64(39.0%) of the MRSA were resistant to 4 classes of antibiotics indicating multi drug resistance (MDR). The overall prevalence of inducible clindamycin resistance among methicillin resistant isolates was 29(17.7%). This implies that 17.7% could have been misidentified as clindamycin susceptible by Kirby-Bauer disk diffusion method. In conclusion prevalence of MRSA was high and it is important to routinely carry out the D-test for detection of inducible clindamycin resistance if clindamycin is considered as a treatment option.

Graphene–Gold Nanostructures Hybrid Composites Screen-Printed Electrode for the Sensitive Electrochemical Detection of Vancomycin

The most important and well-known glycopeptide antibiotic, vancomycin (VAN), is used for the treatment of severe bacterial infections like methicillin-resistant staphylococcal infections and endocarditis caused by enterococci and sepsis. Taking into account the problem of the development of antibiotic resistance as well as its toxicity, both correlated with the VAN concentration (CVAN) in biological samples, there is need for better and more accessible quantification methods for this antibiotic. Considering all of the above, herein, we present a simple electrochemical method for VAN sensing based on a hybrid graphene-gold nanostructure nanocomposite electrode, which allows double detection directly in the oxidation domain and also indirectly, in reduction, using the electro-active gold nanostructures as a probe to monitor the current changing due to the interaction between gold and VAN. The developed method was able to successfully detect VAN in the linear range of 1–100 µM with a limit of detection (LOD) of 0.29 µM for the direct approach and 0.5 µM for the indirect one. The selectivity of the method was tested in the presence of other antibiotics and drugs. This method was successfully applied for the detection of VAN from human serum samples.

Early Bayesian Dose Adjustment of Vancomycin Continuous Infusion in Children: a Randomized Controlled Trial.

Methicillin-resistant staphylococcal infections are a global burden. Area under the serum concentration-time curve to minimum inhibitory concentration (AUC/MIC) ratio is the pharmacokinetic (PK) parameter that best predicts vancomycin efficacy. Its therapeutic range is narrow, difficult to achieve because of a wide intersubject variability, especially in children, and is not routinely targeted since the AUC is rarely available. We investigated if an early Bayesian dose adjustment would increase the rate of vancomycin target attainment, in the first 24 hours of treatment (H24), in children.We conducted a single-centre randomized controlled trial in 4 pediatric departments of Necker-Enfants Malades hospital (Paris, France). Patients aged 3 months to 17 years for whom intravenous vancomycin was started were eligible and randomized in a 1:1 ratio: routine care were compared with an early vancomycin therapeutic drug monitoring (3h after treatment initiation) followed by an early Bayesian dose adjustment using a previously published population-based PK model that included age, bodyweight and serum creatinine as covariates. The primary outcome was the proportion of patients of each group achieving vancomycin therapeutic range at H24, defined by AUC0-24/MIC≥400 and AUC0-24 ≤800mg-h/L.Ninety-nine patients were enrolled: 49 were randomized to the Bayesian group and 50 to the control group. Modified intention-to-treat analysis included 82 patients: 85% of Bayesian group patients achieved H24 vancomycin target versus 57% of control group patients (p=0.007) with no difference regarding iatrogenic events. Early Bayesian dose adjustment increased the proportion of children achieving vancomycin target at H24, which may improve clinical outcomes of methicillin-resistant staphylococcal infections.