Vancomycin Minimum Inhibitory Concentration Research Articles

Reduced Vancomycin Susceptibility in Clostridioides difficile Is Associated With Lower Rates of Initial Cure and Sustained Clinical Response.

Epidemiologic studies have shown decreasing vancomycin susceptibility among clinical Clostridioides difficile isolates, but the impact on patient outcomes is unknown. We hypothesized that reduced vancomycin susceptibility would be associated with decreased rates of sustained clinical response (SCR). This multicenter cohort study included adults with C. difficile infection (CDI) treated with oral vancomycin between 2016 and 2021. Clostridioides difficile isolates underwent agar dilution vancomycin susceptibility testing, ribotyping, and Sanger sequencing of the vancomycin resistance vanR gene. Reduced susceptibility was defined as vancomycin minimum inhibitory concentration (MIC) >2 μg/mL. The primary outcome was 30-day SCR; secondary outcomes were 14-day initial cure, 30-day recurrence, and 30-day mortality. Exploratory analysis assessed the association between the VanR Thr115Ala polymorphism, susceptibility, and outcomes. A high proportion (34% [102/300]) of C. difficile isolates exhibited reduced vancomycin susceptibility (range, 0.5-16 μg/mL; MIC50/90 = 2/4 μg/mL). Ribotype 027 accounted for the highest proportion (77.4% [41/53]) of isolates with reduced vancomycin susceptibility. Overall, 83% (249) of patients achieved 30-day SCR. Reduced vancomycin susceptibility was associated with lower rates of 30-day SCR (76% [78/102]) than vancomycin-susceptible strains (86% [171/198]; P = .031). A significantly lower rate of 14-day initial cure was also observed among individuals infected with strains with reduced vancomycin susceptibility (89% vs 96%; P = .04). Reduced susceptibility remained an independent predictor of 30-day SCR in multivariable modeling (odds ratio, 0.52 [95% confidence interval, .28-.97]; P = .04). Reduced vancomycin susceptibility in C. difficile was associated with decreased odds of 30-day SCR and lower 14-day initial cure rates in the studied patient cohort.

Determination of Vancomycin Minimum Inhibitory Concentration in Methicillin-resistant Staphylococcus Aureus by Various Phenotypic Methods: A Cross-sectional Study

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) has become a global threat, causing nosocomial and community-acquired infections, thus significantly contributing to morbidity and mortality. These organisms often exhibit Multidrug Resistance (MDR) to various groups of antimicrobials. The emergence of reduced susceptibility to vancomycin and resistance further exacerbates the problem, leaving clinicians with few therapeutic options to treat serious, life-threatening infections. Aim: To determine the vancomycin susceptibility of MRSA using various phenotypic methods. Materials and Methods: The present cross-sectional study was conducted in the Department of Microbiology, SHKM Government Medical College, Nalhar, Haryana, India, from February 2019 to January 2020. All MRSA isolates were included, totaling 66 MRSA isolates. MRSA isolates were screened using the cefoxitin disc (30 μg) according to the Clinical and Laboratory Standards Institute (CLSI) recommended disc diffusion method. The Minimum Inhibitory Concentration (MIC) of vancomycin was determined using phenotypic methods such as broth dilution, agar dilution and Epsilometer test (E-test). Demographic details such as age, sex, site of the sample and diagnosis were recorded. Statistical analysis was performed using the Pearson’s product-moment correlation. The significance level was set at a probability of <0.05 with a confidence interval of 95%. Results: A total of 66 (30.3%) isolates of Staphylococcus aureus (S. aureus) were identified as MRSA using standard laboratory tests and were studied for vancomycin MIC using phenotypic methods: Broth dilution, agar dilution and E-test. Vancomycin- intermediate S. aureus (VISA) was observed in 54.5%, 42.4% and 51.5% of MRSA by E-test, agar dilution and broth dilution, respectively. The presence of Vancomycin-resistant S. aureus (VRSA) was not detected in the region. When compared with broth dilution, E-test results demonstrated higher accuracy (97%) than agar dilution (90.9%). Conclusion: The present study highlights the emergence of VISA in more than 40% of the MRSA in the region. The higher MIC of vancomycin emphasises the need for strict adherence to antibiotic prescription guidelines to prevent further emergence of vancomycin resistance.

Characterization of the Pathogen Distribution and Drug Resistance in Bloodstream Infections During COVID-19 Pandemic in a Tertiary Hospital in Eastern China: Comparison with the Pre-Pandemic Period.

To explore the characteristics of the pathogen distribution and drug resistance in bloodstream infections (BSIs) during the COVID-19 pandemic in a tertiary hospital in eastern China, and to compare them with those before the pandemic. Non-repetitive strain data of BSIs were retrospectively obtained before the COVID-19 pandemic (Pre-Pandemic, n=2698) and during the COVID-19 pandemic (Pandemic, n=2922), the distribution of pathogens and drug resistance were compared between the two groups. The main pathogens of BSIs were Gram-negative bacteria (57.91%), followed by Gram-positive bacteria (32.58%), fungi and anaerobic bacteria accounting for 5.48% and 3.39%, respectively. Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus were the top 3 isolates. The proportion of Serratia marcescens, Enterobacter aerogenes, Enterococcus faecium, Enterococcus faecalis and Candida tropicalis were significantly increased, while those of Pseudomonas aeruginosa, Streptococcus sanguinis and Streptococcus pneumoniae were significantly decreased when compared to the Pre-Pandemic (P<0.05). Carbapenem-resistant Enterobacterales (CRE) significantly elevated during the Pandemic (17.4% vs 14.4%, P=0.041); the detection of carbapenem-resistant Pseudomonas aeruginosa (CRPA) significantly ascended (39.0% vs 24.4%, P=0.016); and the proportion of carbapenem-resistant Acinetobacter baumannii (CRAB) maintained stable (78.8%). Gram-positive bacteria had the lowest resistance to linezolid, vancomycin and tigecycline, which remained a stable trend with the Pre-Pandemic (<5.0%). The isolate rates of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) were 38.9% and 1.0%, respectively. Staphylococcus aureus showed a decrease in the isolation rate of vancomycin minimum inhibitory concentration (MIC) ≤ 0.5 μg/mL (χ2=7.676, P=0.006) and an increase with vancomycin MIC=1 μg/mL (χ2=9.008, P=0.003). The pathogen distribution and drug resistance of BSIs during the COVID-19 pandemic were transformed from Pre-Pandemic and accompanied by increasing bacterial resistance. Clinical management of antibiotic application and infection control should be strengthened.

Puerperal mastitis caused by limited community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clones.

To outline the epidemiology of puerperal mastitis caused by methicillin-resistant Staphylococcus aureus (MRSA) and evaluate the effect of an infection control bundle on its incidence. A surge in MRSA puerperal mastitis was noted in a community hospital in September 2009. MRSA samples from mastitis cases and the environment underwent typing using multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec), gene encoding surface protein A (spa), accessory gene regulator (agr), and pulsed-field gel electrophoresis (PFGE). The phenotypic characteristics, including superantigen toxin profiles, gene encoding Panton-Valentine leucocidin (pvl), and minimal inhibitory concentration (MIC) against vancomycin, were ascertained. Subsequently, an infection control bundle emphasizing contact precautions was introduced, and mastitis incidence rates pre- and post-intervention were compared. The majority of cases occurred within 6 weeks post-delivery in first-time mothers. Of the 42 S. aureus isolates (27 from mastitis and 15 from colonized staff and environmental sources), 25 (92.6%) clinical and 3 (20%) colonized MRSA were identified as ST59-SCCmecVT-spa t437-agr group I with a vancomycin MIC of 1 mg/L, pvl-positive, and predominantly with a consistent toxin profile (seb-selk-selr). PFGE revealed 13 patterns; pulsotype B exhibited clonal relatedness between two clinical and three colonized MRSA samples. Post-intervention, the incidence of both mastitis and MRSA mastitis notably decreased from 13.01 to 1.78 and from 3.70 to 0.99 episodes per 100 deliveries, respectively. Distinct community-associated MRSA (CA-MRSA) clones were detected among puerperal mastitis patients and colonized staff. The outbreak was effectively controlled following the implementation of a targeted infection control bundle.

Methicillin-Resistant Staphylococcus aureus Bacteremia Treated With Vancomycin Calculated by Area-Under-the-Curve in Patients With Elevated Vancomycin Minimum Inhibitory Concentrations.

Purpose: Vancomycin is recommended as first-line treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, dosed by area-under-the-curve (AUC) with an assumed minimum inhibitory concentration (MIC) of 1 mcg/mL via broth microdilution. The purpose of this study was to compare effectiveness of AUC-based and trough-based dosing in MRSA bacteremia with an MIC > 1 mcg/mL via Etest. Methods: This was a retrospective, observational cohort that compared vancomycin dosed by AUC or trough between January 1, 2017 and September 1, 2022. The primary outcome was a composite of treatment failure defined as peristent bacteremia ≥ 7 days, inpatient mortality within 90 days, or microbiologic relapse or readmission within 30 days. Secondary outcomes compared nephrotoxicity, hospital and ICU length of stay, MIC differences, and difference in exposure measured by AUC. Results: Twenty-four patients in each group met inclusion criteria. For the primary outcome, there was no statistical difference in treatment failure between trough and AUC groups, respectively [10 (41.7%) vs 10 (41.7%), P = 1.000]. There was no statistical difference in secondary outcomes, with incidence of nephrotoxicity [3 (12.5%) trough vs 2 (8.33%) AUC, P = 1.000] and median AUC exposure over treatment course [502.9 mcg.h/mL (454.1-599.9) vs 474 mcg.h/mL (435.3-533), P = .312] similar between groups. Conclusion: There was no statistically significant difference in treatment failure for vancomycin by AUC or trough with an Etest MIC > 1 mcg/mL. Overall exposure to vancomycin and incidence of nephrotoxicty were numerically higher in the trough group, suggesting that dosing by AUC may limit exposure without impact on treatment failure.

Adaptive cell wall thickening in Enterococcus faecalis is associated with decreased vancomycin susceptibility

ObjectivesEnterococcus faecalis can adopt both a commensal and a nosocomial lifestyle, resisting numerous antibiotics. In this study, we aim to investigate the relationship between the cell wall (CW) thickness and decreased susceptibility to vancomycin (VD) in van-gene negative clinical isolates of E. faecalis (nMIC 8 = 2, nMIC 4 = 3, ST30, ST40, and ST59). MethodsThe CW thickness was assessed in VD strains and compared with vancomycin susceptible isolates of the same sequence type (ST) (Vancomycin susceptible [VS]; nMIC 2 = 5). The VD and VS strains were subjected to serial passage (evolved [ev]) with and without vancomycin selection. Subsequent measurements of CW thickness and vancomycin MICs were performed. ResultsThe VD strains exhibited increased CW thickness when compared with ST-related VS strains (ΔCW thickness VD vs. VS ST30 25 nm, ST59 15 nm, and ST40 1 nm). Serial passages without vancomycin selection led to a decrease in CW thickness and vancomycin MIC in VD strains (ΔCW thickness VD vs. evVD ST30 22 nm, ST59 3 nm, and ST40 2 nm). Serial passages with vancomycin selection caused an increase in CW thickness and vancomycin MIC in ST-related VS strains (ΔCW thickness VS vs. evVS ST30 22 nm, ST59 16 nm, and ST40 1 nm). DiscussionAdaptive changes in CW thickness were observed in response to vancomycin exposure. Increased CW thickness correlated with decreased vancomycin susceptibility, whereas decreased CW thickness correlated with increased vancomycin susceptibility. Core single nucleotide polymorphisms in the evolved mutants were mostly found in genes encoding proteins associated with the cytoplasm or the cytoplasmic membrane. The potential relevance of these adaptive changes is underlined by the observed phenotypes in clinical isolates. Our findings emphasize the importance of monitoring adaptive changes, as vancomycin-resistant enterococci infections are a growing concern.

Molecular and Clinical Features of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus in Tertiary Care Hospitals in South India

Objectives: This study aimed to detect heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) among methicillin-resistant S. aureus (MRSA) isolated from healthcare-associated infections and identify staphylococcal cassette chromosome mec (SCCmec) types. Methods: This study was conducted from February 2019 to March 2020 and included patients admitted in 4 tertiary care hospitals in Karnataka, India. Isolation and identification of MRSA were done using standard bacteriological methods. Antimicrobial susceptibility testing was done using Kirby–Bauer disc diffusion; macrolide-lincosamide-streptogramin B phenotypes were identified using the D test. The minimum inhibitory concentration (MIC) of vancomycin was determined using agar dilution. hVISA were confirmed by the modified population analysis profile-area under the curve test. SCCmec types and the Panton- Valentine leukocidin (pvl) gene were detected using multiplex polymerase chain reaction. Results: Of 220 MRSA stains, 14 (6.4%) were hVISA. None of the MRSA isolates was vancomycin-intermediate or -resistant and all hVISA were susceptible to linezolid and teicoplanin. The macrolide-streptogramin B phenotype was present in 42.9% of hVISA; 92.9% of the hVISA strains had vancomycin MIC in the range of 1–2 μg/mL. Majority of the hVISA and vancomycin-susceptible MRSA were isolated from patients with skin and soft tissue infections. SCCmec III and IV were present in 50% and 35.7% of hVISA, respectively; 14.3% of the hVISA harboured SCCmec V. Conclusion: The prevalence rate of hVISA among MRSA was 6.4%. Therefore, MRSA strains should be tested for hVISA before starting vancomycin treatment. None of the isolates was vancomycin-intermediate or -resistant and all the hVISA strains were susceptible to linezolid and teicoplanin. The majority of the hVISA were isolated from patients with skin and soft tissue infections and harboured SCCmec III and IV. Keywords: MRSA; Hospital Infection; Molecular Typing; Vancomycin; India.

A Comparison of the Minimum Inhibitory Concentration of Antibiotics in Staphylococcus Species Isolated From Orthopedic and Respiratory Medicine Infections.

Antibiotic susceptibility is very important for the successful treatment of orthopedic infections, particularly for implant-related infections. While the minimum inhibitory concentrations (MICs) of Staphylococcus species were well investigated for the isolates from the respiratory tract, investigations for orthopedic pathogens are very limited. We investigated the antibiotic MIC values of Staphylococcus species isolated from orthopedic infections and compared them with those of respiratory medicine isolatesused as a control. The MICs of vancomycin (VCM), arbekacin (ABK), teicoplanin (TEIC), linezolid (LZD), and rifampicin (RFP) of a total of consecutive 259 (89 orthopedic and 170 respiratory) Staphylococcus speciesisolated in our laboratory from January 2013 to July 2016 were retrospectively reviewed. Differences between the MICs of each antibiotic in orthopedic and respiratory samples were determined. The number of methicillin-sensitive Staphylococcus aureus (MSSA) with a VCM MIC of <0.5 μg/mL among respiratory isolates was significantly higher than that among orthopedic isolates, while those with a MIC of 2 μg/mL were significantly lower (P = 0.0078). The proportion of methicillin-resistant coagulase-negative staphylococci (MRCNS) isolates with a VCM MIC of 2 μg/mL was significantly higher in orthopedic samples than that of methicillin-resistant Staphylococcus aureus (MRSA) (P < 0.001) in respiratory isolates. The proportion of MRCNS orthopedic isolates with an RFP MIC of >2 μg/mL was significantly higher (P = 0.0058) than that of other orthopedic staphylococci. The VCM MICs of Staphylococcus species from orthopedic infections were higher than those of respiratory samples, particularly MRCNS from implant-related samples.

In vitro activity of fidaxomicin and combinations of fidaxomicin with other antibiotics against Clostridium perfringens strains isolated from dogs and cats

BackgroundPrevious studies have demonstrated that fidaxomicin, a macrocyclic lactone antibiotic used to treat recurrent Clostridioides difficile-associated diarrhea, also displays potent in vitro bactericidal activity against Clostridium perfringens strains isolated from humans. However, to date, there is no data on the susceptibility to fidaxomicin of C. perfringens strains of animal origin. On the other hand, although combination therapy has become popular in human and veterinary medicine, limited data are available on the effects of antibiotic combinations on C. perfringens. We studied the in vitro response of 21 C. perfringens strains obtained from dogs and cats to fidaxomicin and combinations of fidaxomicin with six other antibiotics.ResultsWhen tested by an agar dilution method, fidaxomicin minimum inhibitory concentrations (MICs) ranged between 0.004 and 0.032 µg/ml. Moreover, the results of Etest-based combination assays revealed that the incorporation of fidaxomicin into the test medium at a concentration equivalent to half the MIC significantly increased the susceptibility of isolates to metronidazole and erythromycin in 71.4% and 61.9% of the strains, respectively, and the susceptibility to clindamycin, imipenem, levofloxacin, and vancomycin in 42.9–52.4% of the strains. In contrast, ¼ × MIC concentrations of fidaxomicin did not have any effect on levofloxacin and vancomycin MICs and only enhanced the effects of clindamycin, erythromycin, imipenem, and metronidazole in ≤ 23.8% of the tested strains.ConclusionsThe results of this study demonstrate that fidaxomicin is highly effective against C. perfringens strains of canine and feline origin. Although fidaxomicin is currently considered a critically important antimicrobial that has not yet been licensed for veterinary use, we consider that the results reported in this paper provide useful baseline data to track the possible emergence of fidaxomicin resistant strains of C. perfringens in the veterinary setting.

Vancomycin versus daptomycin for the treatment of confirmed gram-positive catheter-related bloodstream infections in oncology patients

ObjectiveTo analyse the effectiveness and safety of daptomycin versus vancomycin on the management catheter-related bloodstream infections in oncology patients. MethodA retrospective study was carried out including all patients admitted at the Medical Oncology Unit between 2010 and 2018 with positive blood cultures confirmed catheter-related bloodstream infections due to gram-positive microorganism, who were treated with either vancomycin or daptomycin. The primary end point was all cause 30-days mortality, 30-days hospital readmission and length of hospital stay (length of hospital stay). ResultsA total of 70 patients with catheter-related bloodstream infections were included in the present study: vancomycin was administered to 61.4% (n = 43) and daptomycin to 38.6% (n = 27) of patients. 78.5% (n = 55) of isolated bacteria showed a vancomycin minimum inhibitory concentration ≤ 1 µg/ml. No differences were observed between the two groups of patients regarding the 30-day mortality rate rate (32.6% [n = 14] versus 29.6% [n = 8]; p = 0.797), the 30-day re-admission rate (30.2% [n = 13] versus 29.6°% [n = 8]; p = 0.957) or the length of hospital stay (18.9 versus 16.5 days; p = 0.562). Nephrotoxicity rate was equivalent in both groups: a 7% (n = 3) of vancomycin goup versus a 7.4% (n = 2) of daptomycin group (p = 0.946). ConclusionsOur results show that both antibiotics are equivalent in their safety and effectiveness. Therefore, vancomycin should continue being the treatment of chose for gram-positive catheter-related bloodstream infections, in particular at hospital centres with a low prevalence of strains that show diminished susceptibility to vancomycin.

Detection of Biofilm Production and Antibiotic Resistance Pattern in Clinical Isolates from Orthopaedic Implants Associated Infections

Introduction: Orthopaedic Implant associated infection is the major problem which leads to implant failure and economic burden to the patient. Implant-associated infections are due to the formation of biofilm at the implantation site leading to multidrug resistant organism. Aim: This study was done to evaluate the causative organisms, their antibiotic sensitivity pattern and their ability to form biofilm over the Implants used in Orthopaedic surgeries. Material and methods: This study was carried out in the department of Microbiology, Adichunchanagiri institute of Medical sciences from September 2019 to August 2022. Swabs from 100 patients who had undergone orthopaedic implant or prosthetic surgery and presented with signs and symptoms of infection were collected and processed as per standard procedures. All the isolates were subjected to detect biofilm production by Congo red agar method, MRSA detection by Cefoxitin disc diffusion test, vancomycin resistant Enterococcus by using Vancomycin (Minimum inhibitory concentration) MIC strips and Extended spectrum β lactamases (ESBL) production by phenotypic confirmatory combined-disc test. Results: Out of the 100 samples processed, culture positivity was observed in 72 specimens. Among them, Staphylococcus aureus 19(26%) was the predominant isolate and 44 (61%) are biofilm producers. 17 (89%) were MRSA (Methicillin resistance Staphylococcus aureus) strains and 15(37%) were ESBL producing strains. Conclusion: The appropriate pre- and post- operative care should be taken to prevent orthopaedic implant associated infections. Staphylococcus spp was the commonest isolate and its ability to produce biofilm indicates the need for an appropriate antibiotic policy and screening for MRSA carriers to reduce the infection. Keywords: Orthopaedic implant, Infection, Biofilm, MRSA, ESBL

Profiling daptomycin resistance among diverse methicillin-resistant Staphylococcus aureus lineages in China.

Daptomycin (DAP) is effective against methicillin-resistant Staphylococcus aureus (MRSA). However, reduced susceptibility to DAP in MRSA may lead to treatment failures. We aim to determine the distribution of DAP minimum inhibitory concentrations (MICs) and DAP heteroresistance (hDAP) among MRSA lineages in China. A total of 472 clinical MRSA isolates collected from 2015 to 2017 in China were examined for DAP susceptibility. All isolates (n = 472) were found to be DAP susceptible, but 35.17% (166/472) of them exhibited a high DAP MIC (MIC >0.5 µg/mL). The high DAP MIC group contained a larger proportion of isolates with a higher vancomycin or teicoplanin MIC (>1.5 µg/mL) than the low DAP MIC group (19.3% vs 7.8%, P < 0.001; 22.3% vs 8.2%, P < 0.001). We compared the clonal complex (CC) distributions and clinical characteristics in MRSA isolates stratified by DAP MIC. CC5 isolates were less susceptible to DAP (MIC50 = 1 µg/mL) than CC59 isolates (MIC50 = 0.5 µg/mL, P < 0.001). Population analysis profiling revealed that 5 of 10 ST5 and ST59 DAP-susceptible MRSA isolates investigated exhibited hDAP. The results also showed that CC5 MRSA with an agrA mutation (I238K) had a higher DAP MIC than those with a wild-type agrA (P < 0.001). The agrA-I238K mutation was found to be associated with agr dysfunction as indicated by the loss of δ-hemolysin production. In addition, agr/psmα defectiveness was associated with hDAP in MRSA. Whole-genome sequencing analysis revealed mutations in mprF and walR/walK in DAP-resistant subpopulations, and most DAP-resistant subpopulations (6/8, 75%) were stable. Our study suggests that the increased DAP resistance and hDAP in MRSA may threaten the effectiveness against MRSA infections.

Evaluation of antibiotic susceptibility in enterococci isolated from blood culture samples

Aims: Increased vancomycin resistance in enterococci is an important cause of life-threatening bloodstream infections in hospitalized patients. The aim of this study is to determine the antibiotic susceptibility rates of Enterococcus strains isolated from blood cultures in hospitalized patients in Antalya Training and Research Hospital. &#x0D; Methods: The antibiotic resistance rates of Enterococcus strains isolated from blood cultures of patients hospitalized in the service and intensive care units (ICU) between 1 January 2018 and 30 December 2022 were examined retrospectively. Blood samples were studied with the BacT/ALERT 3D culture system (Biomerieux, France). Bacterial identification was performed using conventional methods, Matrix Assisted Laser Desorption-Ionization Time-of-Flight Mass Spectrometer (MALDI-TOF MS) and VITEK 2 (Biomerieux, France) systems. Antimicrobial susceptibility tests were performed with VITEK 2 (Biomerieux, France) systems. Ampicillin, vancomycin, teicoplanin, high-level gentamicin resistance (HLGR) and linezolid susceptibility of isolated strains were evaluated according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Vancomycin minimal inhibitory concentration (MIC) values of vancomycin resistant strains were studied by microdilution gradient strip test (Bioanalyse).&#x0D; Results: A total of 623 strains of enterococci were isolated from blood culture samples. Of the enterococci, 305 (48.9%) were identified as Enterococcus faecalis, 281 (45.6%) Enterococcus faecium, 12 (1.9%) Enterococcus avium, 11 (1.8%) Enterococcus gallinarum, 7 (1.2%) Enterococcus casseliflavus, 2 (0.4%) Enterococcus durans and 1 Enterococcus hirae (0.2%). Ampicillin and HLGR resistance rates of isolated E. faecalis strains were 11 (3.6%) and 72 (23.6%), respectively, and all strains were found to be susceptible to vancomycin, teicoplanin and linezolid. The ampicillin, vancomycin, teicoplanin and HLGR resistance rates of E. faecium strains were determined as 229 (81.5%), 36 (12.8%), 30 (10.7%) and 142 (50.5%), respectively, and all strains were found to be susceptible to linezolid. &#x0D; Conclusion: In infections caused by enterococci, identification and determination of antibiotic susceptibility rates according to culture antibiogram results would be the right approach. Knowing the current susceptibility rates of enterococci isolated from blood culture samples in our hospital will contribute for clinicians' planning of empirical treatment.

A US-based national surveillance study for the susceptibility and epidemiology of Clostridioides difficile isolates with special reference to ridinilazole: 2020-2021.

We have previously reported on the susceptibility and epidemiology of Clostridioides difficile isolates from six geographically dispersed medical centers in the United States. This current survey was conducted with isolates collected in 2020-2021 from six geographically dispersed medical centers in the United States, with specific attention to susceptibility to ridinilazole as well as nine comparators. C. difficile isolates or stools from patients with C. difficile antibiotic-associated diarrhea were collected and referred to a central laboratory. After species confirmation of 300 isolates at the central laboratory, antibiotic susceptibilities were determined by the agar dilution method [M11-A9, Clinical and Laboratory Standards Institute (CLSI)] against the 10 agents. Ribotyping was performed by PCR capillary gel electrophoresis on all isolates. Ridinilazole had a minimum inhibitory concentration (MIC) 90 of 0.25 mcg/mL, and no isolate had an MIC greater than 0.5 mcg/mL. In comparison, fidaxomicin had an MIC 90 of 0.5 mcg/mL. The vancomycin MIC 90 was 2 mcg/mL with a 0.7% resistance rate [both CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria]. The metronidazole MIC 90 was 1 mcg/mL, with none resistant by CLSI criteria, and a 0.3% resistance rate by EUCAST criteria. Among the 50 different ribotypes isolated in the survey, the most common ribotype was 014-020 (14.0%) followed by 106 (10.3%), 027 (10%), 002 (8%), and 078-126 (4.3%). Ridinilazole maintained activity against all ribotypes and all strains resistant to any other agent tested. Ridinilazole showed excellent in vitro activity against C. difficile isolates collected between 2020 and 2021 in the United States, independent of ribotype.

Genetic alterations in methicillin-susceptible Staphylococcus aureus associated with high vancomycin minimum inhibitory concentration

There are many reports on gene mutations observed in methicillin-resistant Staphylococcus aureus (MRSA) showing reduced susceptibility to vancomycin. However, there are limited studies on the genetic alterations that contribute to high vancomycin minimum inhibitory concentrations (MICs) in methicillin-susceptible S. aureus (MSSA). This study aimed to compare MSSA strains with high vancomycin MICs with those with low MICs, and to identify specific genetic alterations associated with increased vancomycin MICs. In total, 124 MSSA strains were analysed, with 62 having vancomycin MICs of 1-2 mg/L (MS-HV) and the remaining 62 having MICs <1 mg/L (MS-LV) as control. Polymerase chain reaction amplification and sequencing were conducted to identify point mutations and amino acid changes in the vraSR, graRS and walRK operons and rpoB gene. The number of single nucleotide polymorphisms (SNPs) and specific mutations in the indicated gene were compared between the two groups. The MS-HV strains had a significantly higher median number of SNPs in studied genes than the MS-LV strains (5 vs 3; P < 0.0001), with higher frequency of SNPs in the graR and walK genes. The MS-HV strains also displayed a significantly higher prevalence of specific mutations in the graR gene (V135I, I136V and V136I) compared with the MS-LV strains. The odds of having a high vancomycin MIC was 5.54 times higher in strains with a mutation in the graR gene, and 5.32 times higher in strains with a mutation in the walK gene, compared with those without these mutations. Mutations in the graR and walK genes may contribute to reduced vancomycin susceptibility in MSSA. This study gives key insights into the mechanisms underlying this phenomenon.

A statistical genomics framework to trace bacterial genomic predictors of clinical outcomes in Staphylococcus aureus bacteremia

Outcomes of severe bacterial infections are determined by the interplay between host, pathogen, and treatments. While human genomics has provided insights into host factors impacting Staphylococcus aureus infections, comparatively little is known about S.aureus genotypes and disease severity. Building on the hypothesis that bacterial pathoadaptation is a key outcome driver, we developed a genome-wide association study (GWAS) framework to identify adaptive mutations associated with treatment failure and mortality in S.aureus bacteremia (1,358 episodes). Our research highlights the potential of vancomycin-selected mutations and vancomycin minimum inhibitory concentration (MIC) as key explanatory variables to predict infection severity. The contribution of bacterial variation was much lower for clinical outcomes (heritability <5%); however, GWASs allowed us to identify additional, MIC-independent candidate pathogenesis loci. Using supervised machine learning, we were able to quantify the predictive potential of these adaptive signatures. Our statistical genomics framework provides a powerful means to capture adaptive mutations impacting severe bacterial infections.

Association between ratio of area under the concentration–time curve to minimum inhibitory concentration of vancomycin and clinical outcomes in Enterococcus faecium bacteremia

The purpose of this study was to evaluate the relationship between the treatment resolution of Enterococcus faecium bacteremia and the pharmacodynamic targets of vancomycin. This is a retrospective single-center cohort study involving patients with E. faecium bacteremia on vancomycin therapy hospitalized between January 2010 and December 2021. The average vancomycin area under the concentration–time curve (AUC)0 –24 was computed using the Bayesian approach. The minimum inhibitory concentration (MIC) was determined using the broth microdilution method, and The AUC24/MIC value over the initial 24–48 h of therapy was calculated. We assessed 30-day mortality, as the primary outcome. Classification and regression tree analysis (CART) was used to identify the vancomycin AUC24/MIC target associated with 30-day mortality. Eighty-seven patients with E. faecium bacteremia were included in this study, with 14 (16.1%) being non-survivors. In the CART analysis, vancomycin AUC/MIC ≥414.3 was associated with a higher treatment success. In multivariate analysis, an AUC/MIC ≥414.3 was a significant factor for treatment success (adjusted odds ratio = 17.5, 95% confidence interval, 3.7–83.9). Our findings suggest that a target vancomycin AUC/MIC ≥414.3 is a good prognostic indicator and could be useful for treatment monitoring of E. faecium bacteremia.

Biofilm Formation and Antimicrobial Susceptibility Pattern of &lt;i&gt;Staphylococcus aureus&lt;/i&gt; Clinical Isolates from Two Healthcare Facilities in Zaria

Background: Antibiotic resistance is a public health challenge worldwide. There is a huge global concern about the increased drug- resistant S. aureus and the development of multiple resistance to several drugs. A well-designed surveillance study has been found to be a fundamental approach in the control of antimicrobial resistance.&#x0D; Objective: This study investigated the biofilm formation and antimicrobial susceptibility pattern of Staphylococcus aureus from two healthcare facilities in Zaria.&#x0D; Methods: A total of 200 presumptive Staphylococcal isolates from clinical specimens were collected and identified by conventional methods. Staphylococcus aureus isolates were tested against a panel of antibiotics using the modified Kirby- Bauer disk diffusion method, Methicillin-resistant Staphylococcus aureus (MRSA) were tested using cefoxitin disk, and Micro broth dilution method for Vancomycin Minimum Inhibitory Concentration (MIC). The biofilmforming ability of the isolates were analyzed quantitatively using the microtitre plate method.&#x0D; Results: Of the 200 presumptive staphylococcal isolates, 22(11%) were Staphylococcus aureus. The antibiotic resistance pattern of the isolates shows high resistance to tigecycline (100%), vancomycin (100%), clindamycin (40.9%), and tetracycline (40.9). The occurrence of MRSA in this study was 18.8% and MDR (was 68.2%). The biofilm-forming ability of the Staphylococcus aureus isolates is; weak biofilm formers 16 (72.7%), moderate biofilm formers 5 (22.7%), and strong biofilm former 1 (4.5%).&#x0D; Conclusion: There is need for more research to ascertain the relationship between biofilm formation and antimicrobial resistance in Staphylococcus aureus. Close monitoring of antimicrobial resistance is necessary as it helps to design tangible actions that will yield the greatest impact to control the spread of resistant organisms.

Emergence of clinical &lt;i&gt;vanA&lt;/i&gt;-type vancomycin-resistant &lt;i&gt;Staphylococcus aureus&lt;/i&gt; isolates in National Orthopaedic Hospital Dala, Kano, Nigeria

Background: The increasing prevalence of multi drug resistance (MDR) in strains of Staphylococcus aureus is a major challenge in the selection of an appropriate therapeutic agents, especially in persistent orthopaedic infections. This study investigated the patterns of antimicrobial resistance and identified the genetic determinants of resistance in S. aureus isolates from orthopaedic patients.&#x0D; Methodology: This was a descriptive cross-sectional study of hospitalized patients at National Orthopaedic Hospital Dala (NOHD), Kano, Nigeria from whom urine samples, and nasal and wound swabs were collected for isolation of S. aureus. Samples were cultured on standard media and S. aureus isolated and identified using both conventional biochemical tests and a standard rapid diagnostic kit. The antibiotic susceptibility was determined to a panel of 15 antibiotics using the modified Kirby-Bauer disc diffusion method. Vancomycin minimum inhibitory concentration (MIC) of each isolate was determined using vancomycin Epsilon-test strip. mecA and vanA were detected by multiplex polymerase chain reaction (PCR) assay.&#x0D; Results: From the total of 134 samples, S. aureus was isolated from 36 (26.8%); 10 (7.4%) from urine, 13 (9.7%) from nasal swab, and 13 (9.7%) from wound swab. Thirty-four (94.4%) isolates were phenotypically methicillin (cefoxitin) resistant (MRSA), while 2 (5.6%) isolates were methicillin sensitive (MSSA). Phenotypic resistance rate of the S. aureus isolates was highest to gentamicin (94.4%), followed by penicillin (88.8%), cephalosporins and fluoroquinolones (87.4%), while rate was lowest to vancomycin (11.1%, 4/36). Seventeen (47.2%) were MDR, 16 (44.4%) were extensively drug resistant (XDR), and 2 (5.6%) were pan-drug resistant (PDR) S. aureus isolates. The mecA gene was detected in 4 (11.8%) of the 34 phenotypic MRSA isolates and vanA genes in 2 (50.0%) of the 4 phenotypic VRSA isolates.&#x0D; Conclusion: The detection of vanA and mecA in clinical S. aureus isolates in this study is an indication that clinical VRSA has emerged in MRSA population in Nigeria. This emergence can pose a major threat to primary care-givers and a public health challenge among the daily inhabitants of National Orthopaedic Hospital Dala (NOHD), Kano and the community at large.

SPECIATION AND ANTIMICROBIAL SUSCEPTIBILITY OF ENTEROCOCCI FROM PATIENTS IN A TERTIARY CARE HOSPITAL

Introduction: Enterococci have evolved from normal commensals to multidrug resistant pathogen. Enterococci are often reported in association with hospital-acquired infections. Management of Enterococcal infections has become challenging due to the emergence of multidrug resistant strains. Objectives: To speciate and detect the antibiotic susceptibility of Enterococci isolated from different clinical specimens.Materials and Methods: Atotal of 100 Enterococci strains isolated from clinical samples were tested using standard microbiological procedures. The minimum inhibitory concentration (MIC) for vancomycin was tested by agar dilution and E-strip methods. Results: Enterococci infections were more common in age groups, 21-40 years and 41-60 years with male preponderance. Isolates of Enterococci were more frequently associated with post operative wound infection (26%). E. faecalis (55%) was the predominant species, followed by E. faecium (45%). E. faecium showed 80% resistance to penicillin and ampicillin, while E. faecalis showed 38% resistance. All Enterococci isolates were 100% sensitive to vancomycin, linezolid and teicoplanin by the disc diffusion method; however, MIC for vancomycin by agar dilution and E-strip methods showed one strain of E. faecium resistant to vancomycin. Conclusion: Enterococci identication to the species level should be stressed in routine laboratory practice. Vancomycin resistance detection in Enterococci by the MIC method should be preferred as it helps reduce the morbidity and mortality due to Vancomycin resistant Enterococci.