Panel Of Antibiotics Research Articles

BlaGES-producing ST654 comprises a quarter of all carbapenem-resistant Pseudomonas aeruginosa in blood isolates from 15 hospitals.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) are of major clinical concern. We analyzed 85 P. aeruginosa blood isolates non-susceptible to carbapenems collected during 2021-2023 from 15 medical centers in Israel. We aimed to determine the prevalence of high-risk clones, examine clonality, test antibiotic susceptibility, and assess the presence of acquired resistance genes, including carbapenemases. Whole-genome sequencing was performed using Illumina sequencing technology. Susceptibly was determined using the broth microdilution method. In the entire sample, 43.5% were high-risk clones. A main clade (27.1% of isolates) found in multiple hospitals comprised 19 isolates belonging to the high-risk ST654 clone and four closely related isolates. The isolates in this main clade harbored a broad set of resistance genes, including GES-type genes, and 91% had a mutated outer membrane protein (OprD). Isolates in the main clade were uniformly tobramycin (TOB) resistant and 83% were ceftolozane/tazobactam resistant. In the entire sample, we found high resistance to most antipseudomonal agents, including new beta-lactam/beta-lactamase inhibitor combinations. No uniform susceptibility to an antipseudomonal agent was found. Carbapenemases were carried by 9.4% of isolates (5.9% blaGES-5 and 3.5% blaNDM-1) and oprD was mutated in 67% of isolates. Thus, the epidemiology of CRPA is explained by a combination of clonal expansion of a dominant high-risk clade and sporadic occurrence of mutated strains. Our findings highlight the importance of susceptibility testing using a wide panel of antibiotics when CRPA is detected. Prevention measures tracking and controlling emerging high-risk clades and clones are crucial to limit the spread of CRPA.

Occurrence and characterization of ESKAPE organisms on the hands of veterinary students before patient contact at a veterinary academic hospital, South Africa

ObjectiveThis study aimed to investigate the presence of ESKAPE organisms on the hands of students working in the intensive care unit (ICU) at a veterinary academic hospital.MethodsA cross-sectional study was conducted among students working in an ICU at a veterinary academic hospital in South Africa. Students were sampled before the start of the ICU shift using a modified glove-juice method. Standard microbiological techniques and a series of polymerase chain reaction (PCR) assays were used to identify and characterize the bacteria. All the isolates were tested for resistance against a specific panel of antibiotics using the disk diffusion method. Proportions of bacterial species and their antimicrobial-susceptibility profiles were calculated.ResultsAt screening, all the veterinary students (n = 62) carried at least one of the ESKAPE organisms on their hands. Escherichia coli was the most isolated organism (76%, 47/62), followed by P. aeruginosa (48%, 30/62), A. baumannii (47%, 29/62), E. faecium (35%, 22/62), K. pneumoniae (27%, 17/62), and S. aureus (24%, 15/62). A reduced proportion of isolates were recovered from the samples, E. coli (26%, 12/47), E. faecium (23%, 5/22), P. aeruginosa (43%, 13/30), A. baumannii (24%,7/29), K. pneumoniae (41%, 7/17), and S. aureus (20%, 3/15). Most of the organisms showed a high proportion of resistance to at least one antibiotic. Multidrug resistance was reported among just over half (56%, 5/9) of E. coli, 40% (2/5) of E. faecium, 100% (13/13) of P. aeruginosa, and 33% (1/3) of S. aureus isolates.ConclusionStudents working in the ICU carry several organisms belonging to the ESKAPE group of organisms before contact with patients. Moreover, MDR resistance was common among this group of organisms. The findings of the present study underscore the importance of infection prevention and control (IPC) strategies to help reduce the likelihood of the spread of these organisms to personnel, owners, family members, and patients.

Modulating Microbial Resistance: Transcription Factor Regulation of Antibiotic Resistance in Escherichia coli

Abstract Introduction/Objective Antibiotic resistance is a global health emergency, with resistance detected to all antibiotics currently in clinical use and only a few novel drugs in the development pipeline. Antibiotics target key biological processes in bacteria, such as protein synthesis, cell wall synthesis, DNA replication and protein translation. Cells tightly control their internal states in different environments by regulating their transcriptional program through the activity of transcription factors (TFs) that control the expression of multiple downstream effector genes. We hypothesized that efficacy of specific antibiotics can be adjusted by altering the transcriptional states of bacteria prior to treatment, using TF knockout (KO) and over- expression (O-E) strains. Methods/Case Report Aim: Calculate the IC50 of 9 TF KO strains and 9 TF O-E strains across across a panel of representative antibiotics. A previous barcode screen study had identified TF KOs which were associated with antibiotic resistance/susceptibility. A serial antibiotic dilution was prepared in M9 media. E. coli TF KO and O-E strains were cultured for 24 hours in M9 media+Antibiotic (37°C, shaking). Each strain/antibiotic combination contained a technical replicate. Growth was measured by OD, allowing for calculation of growth curves, drug response curves, IC50, and EC50. Strain-specific IC50 and EC50 were compared to wild-type (WT) IC50 and EC50 as a measure of drug resistance/susceptibility. Results (if a Case Study enter NA) Experiments demonstrated consistent, TF-specific patterns of drug susceptibility. Compared to WT, TF KO strains demonstrated altered antibiotic IC50s (drug susceptibility). Compared to WT, TF O-E strains also demonstrated altered antibiotic IC50s (drug susceptibility). Conclusion Hypothesis Weakly Supported – TF states affect IC50s (Abx resistance). The relationships outlined in initial screen were consistently represented in experimental trials. Strain resistance/susceptibility is directly related to TF system and drug mechanism of action. For example, drugs that inhibited ribosomal function demonstrated greater effectiveness against KO/O-E strains that relied more heavily on protein synthesis pathways. Drug resistance is not binary but is shaped by a number of internal cellular factors, including gene regulation by TFs.

Assessment of carbapenem resistance and carbapenemase genes in wastewater from cattle slaughterhouses: Implications for environmental antibiotic resistance surveillance

The objectives of the study were to determine the prevalence of carbapenem-resistant Gram-negative bacteria and assess the potential risks associated with cattle slaughterhouse wastewater. A total of 270 wastewater samples were collected from 10 different cattle slaughterhouses for microbiological analysis. Conventional culture methods were employed, followed by disc diffusion, the Modified Carbapenem Inactivation Method (mCIM), and the Modified Hodge Test (MHT) to identify carbapenem resistance. The Vitek® 2 compact system was used for species identification and antibiotic susceptibility profiling. Conventional and quantitative PCR (qPCR) were performed to detect specific carbapenemase genes (blaKPC, blaNDM, and blaOXA-48). Among the collected 72 carbapenem-resistant isolates, one Pseudomonas fluorescens, one Aeromonas hydrophila, and two Aeromonas sobria exhibited resistance to meropenem. Additionally, six P. fluorescens and two A. hydrophila isolates demonstrated intermediate resistance to meropenem. Furthermore, five carbapenem-resistant isolates were identified as Stenotrophomonas maltophilia, known to be inherently resistant to most antibiotics. Ten different antibiotics were evaluated in the antibiotic resistance panel and all Aeromonas isolates were found to be resistant to cefazolin and one A. hydrophila was detected as multi-drug resistant. The revealed data indicates that slaughterhouse wastewater can serve as a reservoir for antibiotic-resistant opportunistic pathogens. However, it may not pose a substantial risk for the distribution of carbapenemases, thereby mitigating concerns related to potential public health and environmental hazards associated with this aspect of slaughterhouse operations. This study contributes to understanding of antibiotic resistance in livestock-related environments and underscores the importance of continued monitoring and surveillance.

Nitrofurantoin susceptibility profile versus other antibiotics tested in uropathogens- a retrospective study from India

Introduction. Urinary Tract Infection (UTI) is one of the most common bacterial infections encountered by clinicians worldwide. The emergence of multidrug-resistant uropathogens necessitates a review of their susceptibility profiles. This study aims to assess the susceptibility trends of uropathogens to a panel of drugs, with special emphasis on Nitrofurantoin (NFT). Methods. A retrospective analysis was conducted on 2,099 mid-stream clean catch urine samples processed by standard microbiological methods. Clinical and Laboratory Standards Institute (CLSI) guidelines (2019) were followed. Statistical analysis was performed. Results. Out of all samples, 212 were culture positive. Escherichia coli (34.9%) and Enterococcus spp. (15.1%) were the most common Gram-negative and Gram-positive organisms, respectively. Gram-negative isolates were most susceptible to Colistin (97.38%), followed by NFT (69.35%). Gram-positive uropathogens were most sensitive to Linezolid (100%), followed by Vancomycin and NFT, each with 92.45% susceptibility. Conclusion. The increase in antibiotic resistance among various uropathogens underscores the need for surveillance data to inform the appropriate selection of antibiotics. Our study highlights that, among the panel of antibiotics tested, NFT appears to be a viable alternative for treating multidrug-resistant uropathogens.

A 10-year Retrospective Review of Patient-to-Patient Transmitted Pathogens in Culture-Positive Burn Wounds at a Tertiary Burn Center

Introduction: Burn wound infection can progress to sepsis and is a significant source of morbidity and mortality. Prevalence of multidrug-resistant organisms are high in burn patients; these organisms can be transmitted between patients leading to poor outcomes. Objectives: To characterize patient-to-patient transmission of pathogens causing burn wound colonization at a single tertiary hospital burn center in Hamilton, Canada from 2011 to 2020. Methods: Retrospective chart review of patients admitted to the burn trauma unit at Hamilton General Hospital between 2011 and 2020. Antibiotic susceptibility panels of pathogens cultured from burn patients’ wound swab/tissue cultures were compared against pathogens cultured from other burn/nonburn patients with overlapping admission dates. Pathogens were categorized into likely, possible, or unlikely transmission, or normal skin flora on a case-by-case basis. Results: There were 173 burn patients with positive wound culture and 613 nonburn patients included in the study. Included burn patients had median age 52 years, mostly male (73%) with flame injury (65%), and median total body surface area 18%. There were 18 patients (10%) with likely transmission and 54 patients (31%) with possible transmission. Most frequently implicated pathogens for likely patient-to-patient transmission were methicillin-resistant Staphylococcus aureus (MRSA) (7 patients) and methicillin-resistant coagulase-negative Staphylococci (4 patients). Both burn and nonburn patients were implicated. Conclusion: The burden of patient-to-patient transmission in culture-positive burn wounds was estimated to be between 10% and 41%. Greater care should be taken to avoid patient-to-patient transmission of pathogens to minimize burn infection morbidity and mortality. Prospective studies should be conducted with genomic sequencing and correlation with clinical outcomes.

Cell envelope structural and functional contributions to antibiotic resistance in Burkholderia cenocepacia.

Antibiotic activity is limited by the physical construction of the Gram-negative cell envelope. Species of the Burkholderia cepacia complex (Bcc) are known as intrinsically multidrug-resistant opportunistic pathogens with low permeability cell envelopes. Here, we re-examined a previously performed chemical-genetic screen of barcoded transposon mutants in B. cenocepacia K56-2, focusing on cell envelope structural and functional processes. We identified structures mechanistically important for resistance to singular and multiple antibiotic classes. For example, susceptibility to novobiocin, avibactam, and the LpxC inhibitor, PF-04753299, was linked to the BpeAB-OprB efflux pump, suggesting these drugs are substrates for this pump in B. cenocepacia. Defects in peptidoglycan precursor synthesis specifically increased susceptibility to cycloserine and revealed a new putative amino acid racemase, while defects in divisome accessory proteins increased susceptibility to multiple β-lactams. Additionally, disruption of the periplasmic disulfide bond formation system caused pleiotropic defects on outer membrane integrity and β-lactamase activity. Our findings highlight the layering of resistance mechanisms in the structure and function of the cell envelope. Consequently, we point out processes that can be targeted for developing antibiotic potentiators.IMPORTANCEThe Gram-negative cell envelope is a double-layered physical barrier that protects cells from extracellular stressors, such as antibiotics. The Burkholderia cell envelope is known to contain additional modifications that reduce permeability. We investigated Burkholderia cell envelope factors contributing to antibiotic resistance from a genome-wide view by re-examining data from a transposon mutant library exposed to an antibiotic panel. We identified susceptible phenotypes for defects in structures and functions in the outer membrane, periplasm, and cytoplasm. Overall, we show that resistance linked to the cell envelope is multifaceted and provides new targets for the development of antibiotic potentiators.

Genomic Characteristics of an Extensive-Drug-Resistant Clinical Escherichia coli O99 H30 ST38 Recovered from Wound.

Antibiotic-resistant Escherichia coli is one of the major opportunistic pathogens that cause hospital-acquired infections worldwide. These infections include catheter-associated urinary tract infections (UTIs), ventilator-associated pneumonia, surgical wound infections, and bacteraemia. To understand the mechanisms of resistance and prevent its spread, we studied E. coli C91 (ST38), a clinical outbreak strain that was extensively drug-resistant. The strain was isolated from an intensive care unit (ICU) in one of Kuwait's largest hospitals from a patient with UTI. This study used whole-genome sequencing (Illumina, MiSeq) to identify the strain's multi-locus sequence type, resistance genes (ResFinder), and virulence factors. This study also measured the minimum inhibitory concentrations (MIC) of a panel of antibiotics against this isolate. The analysis showed that E. coli C-91 was identified as O99 H30 ST38 and was resistant to all antibiotics tested, including colistin (MIC > 32 mg/L). It also showed intermediate resistance to imipenem and meropenem (MIC = 8 mg/L). Genome analysis revealed various acquired resistance genes, including mcr-1, bla CTX-M-14, bla CTX-M-15, and bla OXA1. However, we did not detect bla NDM or bla VIM. There were also several point mutations resulting in amino acid changes in chromosomal genes: gyrA, parC, pmrB, and ampC promoter. Additionally, we detected several multidrug efflux pumps, including the multidrug efflux pump mdf(A). Eleven prophage regions were identified, and PHAGE_Entero_SfI_NC was detected to contain ISEc46 and ethidium multidrug resistance protein E (emrE), a small multidrug resistance (SMR) protein family. Finally, there was an abundance of virulence factors in this isolate, including fimbriae, biofilm, and capsule formation genes. This isolate has a diverse portfolio of antimicrobial resistance and virulence genes and belongs to ST38 O99 H30, posing a serious challenge to treating infected patients in clinical settings.

Amikacin once every other day versus Daily Meropenem for Treatment of Urinary Tract Infection with Escherichia Coli

Background and Aim: Urinary tract infection (UTI) is a common medical challenge, especially in the light of increased antibiotic resistance. This work aimed to compare between amikacin (3 doses, once each other day) with a daily dose of meropenem (once daily for seven days) for the treatment of urinary tract infection caused by Escherichia Coli. 
 Patients and Methods: 70 patients with confirmed UTI infection by E. Coli were included and divided for two groups. The first was treated by amikacin 15mg/kg once every 48 hours for seven days. The second group was treated by meropenem 1 g three times daily for one week. Then, urinary culture and sensitivity was re-performed and tested against the commonest panel of antibiotics. The clinical manifestations were documented before treatment and one week after treatment.
 Results: There was no significant difference between groups regarding patient demographics or manifestations of UTI. 54.3% in amikacin and 65.7% in meropenem groups reported previous UTI. The clinical manifestations of UTI include dysuria, frequent urination, flank pain, abdominal pain, fever and suprapubic pain. The treatment was associated with eradication of E. Coli in 60.0% and 54.3% in Amikacin and meropenem respectively, with no significant differences between groups at the end of the first week and at that time, the most sensitive drugs were nitrofurantoin (34.3%) followed by meropenem (22.9%) and amikacin (18.6%). However, the highest resistance was registered for cefepime and cefotaxime (41.4%) followed by ceftazidime-clavulanic acid (40.0%). Clinical manifestations of UTI were significantly reduced in both groups one week after treatment with no significant differences between groups.
 Conclusion: Amikacin could be considered as is an effective and safe alternative to meropenem for treatment of UTI due to E. Coli.

Emergence of carbapenem resistant gram-negative pathogens with high rate of colistin resistance in Egypt: A cross sectional study to assess resistance trends during the COVID-19 pandemic

The current study investigated the temporal phenotypic and genotypic antimicrobial resistance (AMR) trends among multi-drug resistant and carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa recovered from Egyptian clinical settings between 2020 and 2021. Bacterial identification and antimicrobial sensitivity of 111 clinical isolates against a panel of antibiotics were performed. Molecular screening for antibiotic resistance determinants along with integrons and associated gene cassettes was implemented. An alarming rate (98.2%) of these isolates were found to be phenotypically resistant to carbapenem. Although 23.9 % K. pneumoniae isolates were phenotypically resistant to colistin, no mobile colistin resistance (mcr) genes were detected. Among carbapenem-resistant isolates, blaNDM and blaOXA-48-like were the most prevalent genetic determinants and were significantly overrepresented among K. pneumoniae. Furthermore, 84.78% of K. pneumoniae isolates co-produced these two carbapenemase genes. The plasmid-mediated quinolone resistance genes (qnrS and qnrB) were detected among the bacterial species and were significantly more prevalent among K. pneumoniae. Moreover, Class 1 integron was detected in 82% of the bacterial isolates. This study alarmingly reveals elevated resistance to last-resort antibiotics such as carbapenems as well as colistin which impose a considerable burden in the health care settings in Egypt. Our future work will implement high throughput sequencing-based antimicrobial resistance surveillance analysis for characterization of novel AMR determinants. This information could be applied as a step forward to establish a robust antibiotic stewardship program in Egyptian clinical settings, thereby addressing the rising challenges of AMR.

High frequency of antimicrobial resistance in Salmonella and Escherichia coli causing diarrheal diseases at the Yirimadio community health facility, Mali

BackgroundDiarrhoea is a public health problem, especially in developing countries where it is the second leading cause of child mortality. In Low Income Countries like in Mali, self-medication and inappropriate use of antibiotics due to the scarcity of complementary diagnostic systems can lead to the development of multidrug-resistant bacteria causing diarrhoea. The objective of this work was to determine the microorganisms responsible for diarrhoea in children under 15 years of age and to characterize their sensitivity to a panel of antibiotics used in a peri-urban community in Mali. The study involved outpatient children visiting the Yirimadio Community Health Centre and diagnosed with diarrhoea. Stool samples from those patients were collected and analysed by conventional stools culture and the susceptibility to antibiotics of detected bacteria was determined by the disc diffusion method in an agar medium.ResultOverall, 554 patients were included. Children under the age of 3 years accounted for 88.8% (492 of 554) of our study population. Two bacterial species were isolated in this study, Escherichia coli 31.8% (176 of 554) and Salmonella 2.9% (16 of 554). In the 176, E. coli strains resistance to amoxicillin and to cotrimoxazole was seen in 93.8% (165 of 176) and 92.6% ( 163 of 176), respectively. The ESBL resistance phenotype accounted for 39,8% (70 of 176) of E. coli. Sixteen (16) strains of Salmonella were found, of which one strain (6.3%) was resistant to amoxicillin and to amoxicillin + clavulanic acid. Another one was resistant to chloramphenicol (6.3%). Two strains of Salmonella were resistant to cotrimoxazole (12.5%) and two others were resistant to cefoxitin (12.5%).ConclusionsThe data suggest that E. coli is frequently involved in diarrhoea in children under 3 years of age in this peri-urban setting of Bamako, Mali, with a high rate of resistance to amoxicillin and cotrimoxazole, the most widely used antibiotics in the management of diarrhoea in this setting.

Comparative molecular profiling of multidrug-resistant Pseudomonas aeruginosa identifies novel mutations in regional clinical isolates from South India.

We sought to analyse the antibiotic susceptibility profiles and molecular epidemiology of MDR clinical Pseudomonas aeruginosa isolates from South India using non-MDR isolates as a reference. We established a comprehensive clinical strain library consisting of 58 isolates collected from patients across the South Indian state of Kerala from March 2017 to July 2019. The strains were subject to antibiotic susceptibility testing, modified carbapenem inactivation method assay for carbapenemase production, PCR sequencing, comparative sequence analysis and quantitative PCR of MDR determinants associated with antibiotic efflux pump systems, fluoroquinolone resistance and carbapenem resistance. We performed in silico modelling of MDR-specific SNPs. Of our collection of South Indian P. aeruginosa clinical isolates, 74.1% were MDR and 55.8% were resistant to the entire panel of antibiotics tested. All MDR isolates were resistant to levofloxacin and 93% were resistant to meropenem. We identified seven distinct, MDR-specific mutations in nalD, three of which are novel. mexA was significantly overexpressed in strains that were resistant to the entire test antibiotic panel while gyrA and gyrB were overexpressed in MDR isolates. Mutations in fluoroquinolone determinants were significantly associated with MDR phenotype and a novel GyrA Y100C substitution was observed. Carbapenem resistance in MDR isolates was associated with loss-of-function mutations in oprD and high prevalence of NDM (blaNDM-1) within our sample. This study provides insight into MDR mechanisms adopted by P. aeruginosa clinical isolates, which may guide the potential development of therapeutic regimens to improve clinical outcomes.

Pyridylpiperazine efflux pump inhibitor boosts in vivo antibiotic efficacy against K. pneumoniae

Antimicrobial resistance is a global problem, rendering conventional treatments less effective and requiring innovative strategies to combat this growing threat. The tripartite AcrAB-TolC efflux pump is the dominant constitutive system by which Enterobacterales like Escherichia coli and Klebsiella pneumoniae extrude antibiotics. Here, we describe the medicinal chemistry development and drug-like properties of BDM91288, a pyridylpiperazine-based AcrB efflux pump inhibitor. In vitro evaluation of BDM91288 confirmed it to potentiate the activity of a panel of antibiotics against K. pneumoniae as well as revert clinically relevant antibiotic resistance mediated by acrAB-tolC overexpression. Using cryo-EM, BDM91288 binding to the transmembrane region of K. pneumoniae AcrB was confirmed, further validating the mechanism of action of this inhibitor. Finally, proof of concept studies demonstrated that oral administration of BDM91288 significantly potentiated the in vivo efficacy of levofloxacin treatment in a murine model of K. pneumoniae lung infection.

2952. Impacts of an evidence-based, pre-populated order panel on antimicrobial prescribing trends in ambulatory patients with community-acquired pneumonia

Abstract Background Optimizing antimicrobial regimens for outpatients with community-acquired pneumonia (CAP) represents an area of opportunity for ambulatory antimicrobial stewardship programs. A pre-populated, antibiotic order panel for outpatient respiratory syndromes was implemented in the Mayo Clinic Enterprise on 1/4/2021. For CAP, it provides national guideline adherent regimens (i.e., selection, dosing, and durations) by patient comorbidity and beta-lactam allergy status. We aimed to assess impacts of panel use on antibiotic prescribing in outpatients with CAP. Methods This retrospective review included Mayo Clinic outpatient encounters from Minnesota in 2021 and 2022. Eligible encounters used a CAP-related primary ICD-10 code, conveyed intention to treat CAP in encounter notes, and were performed by primary care, emergency department, or urgent care clinicians who managed ≥1 CAP patient with the panel and ≥1 without the panel during the study period. Encounters were excluded if patients were already receiving antibiotics at the time of encounter. The primary outcome was adherence (drug and duration) to guideline recommendations. Secondary outcomes included utilization rate by agent and therapy duration. Outcomes were analyzed with Kruskal-Wallis rank sum and Pearson’s chi-squared tests (α level = 0.05). Results 352 encounters (134 panel vs. 218 non-panel) were included. Prescribing was guideline adherent in 61.9% and 29.4% (p< 0.01) of panel and non-panel encounters, respectively. The most common reason for guideline non-adherence during panel use was inappropriate drug selection (n = 45/51, 88.2%). This was predominantly driven by use of the incorrect section of the treatment panel based on patient comorbidity status (n = 30/45, 66.7%). Individual antibiotic utilization rates differed between panel and non-panel cohorts (Table 1), with higher rates of amoxicillin and amoxicillin/clavulanate use and lower rates of azithromycin and doxycycline use in the panel cohort. Durations >5 days were more common in the non-panel as compared to the panel cohort (34.4% vs. 7.5%, p < 0.01). Conclusion Use of a pre-populated antimicrobial order panel in outpatients with CAP resulted in greater adherence to national guideline recommendations. Disclosures Paschalis Vergidis, MD, MSc, AbbVie: Advisor/Consultant|Ansun: Grant/Research Support|Cidara: Grant/Research Support|Scynexis: Grant/Research Support

Monitoring the battleground: exploring antimicrobial resistance and virulence factors in wound bacterial isolates.

Antibiotic resistance poses a grave global public health threat, exacerbated by widespread and often inappropriate antibiotic usage. Vigilant surveillance of antibiotic utilization and emergence of antimicrobial resistance (AMR) is essential. Of particular concern in the era of AMR is the persistent issue of chronic wound infections. To address this, we conducted a comprehensive evaluation of wound isolates from chronic wounds at Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH) in Kenya, to identify relevant bacteria and assess their drug resistance patterns.Wound samples were collected and processed using standard microbiological methods. Bacterial isolates were identified and assessed for their susceptibility to a panel of antibiotics using the Kirby-Bauer disk diffusion method. A total of 103 bacterial isolates were obtained from the wound samples, with a higher prevalence in male patients (59%). Staphylococcus aureus (20.7 %) emerged as the most predominant pathogen, followed by Klebsiella spp. (14.8 %), Pseudomonas aeruginosa spp. (14.8 %) and Escherichia coli (4.4 %) in wound samples. High levels of antibiotic resistance were observed among the isolates, with the highest resistance rates reported for cotrimoxazole (48.1 %), clindamycin (25.9 %) and erythromycin (25.9 %). Furthermore, among the isolates, 75 % produced haemolysin and protease, while 50 % produced lipase and phospholipase, factors that enhance virulence and survival. The findings of this study highlight the alarmingly high prevalence of antibiotic resistance among bacterial pathogens isolated from chronic wounds in Kenya. This poses a major challenge to the effective management of chronic wound infections. There is an urgent need to implement effective antimicrobial stewardship programs and develop new antibiotics to combat the growing threat of antibiotic resistance.

Antibiotic resistance and virulence genes profiling of Vibrio cholerae and Vibrio mimicus isolates from some seafood collected at the aquatic environment and wet markets in Eastern Cape Province, South Africa.

The current study determines the density of Vibrio spp. and isolates V. cholerae and Vibrio mimicus from fish-anatomical-sites, prawn, crab and mussel samples recovered from fish markets, freshwater and brackish water. Virulence and antibiotic resistance profiling of isolates were carried out using standard molecular and microbiology techniques. Vibrio spp. was detected in more than 90% of samples [134/144] and its density was significantly more in fish than in other samples. Vibrio. cholerae and V. mimicus were isolated in at least one sample of each sample type with higher isolation frequency in fish samples. All the V. cholerae isolates belong to non-O1/non-O139 serogroup. One or more V. cholerae isolates exhibited intermediate or resistance against each of the eighteen panels of antibiotics used but 100% of the V. mimicus were susceptible to amikacin, gentamycin and chloramphenicol. Vibrio cholerae exhibited relatively high resistance against polymyxin, ampicillin and amoxicillin/clavulanate while V. mimicus isolates exhibited relatively high resistance against nitrofurantoin, ampicillin and polymixin. The multiple-antibiotic-resistance-index [MARI] for isolates ranges between 0 and 0.67 and 48% of the isolates have MARI that is >0.2 while 55% of the isolates exhibit MultiDrug Resistance Phenotypes. The percentage detection of acc, ant, drf18, sul1, mcr-1, blasvh, blaoxa, blatem, blaoxa48, gyrA, gyrB and parC resistance-associated genes were 2%, 9%, 14%, 7%, 2%, 25%, 7%, 2%, 2%, 32%, 25% and 27% respectively while that for virulence-associated genes in increasing other was ace [2%], tcp [11%], vpi [16%], ompU [34%], toxR [43%], rtxC [70%], rtxA [73%] and hyla [77%]. The study confirmed the potential of environmental non-O1/non-O139 V. cholerae and V. mimicus to cause cholera-like infection and other vibriosis which could be difficult to manage with commonly recommended antibiotics. Thus, regular monitoring of the environment to create necessary awareness for this kind of pathogens is important in the interest of public health.

Exploring Antibiotic-Potentiating Effects of Tobramycin-Deferiprone Conjugates in Pseudomonas aeruginosa.

Metal ions, including Fe3+, affect the target site binding of some antibiotics and control the porin- and siderophore-mediated uptake of antibiotics. Amphiphilic tobramycins are an emerging class of antibiotic potentiators capable of synergizing with multiple classes of antibiotics against Gram-negative bacteria, including Pseudomonas aeruginosa. To study how the antibiotic-potentiating effect of amphiphilic tobramycins is affected by the presence of intermolecular iron chelators, we conjugated the FDA-approved iron chelator deferiprone (DEF) to tobramycin (TOB). Three TOB-DEF conjugates differing in the length of the carbon tether were prepared and tested for antibacterial activity and synergistic relationships with a panel of antibiotics against clinical isolates of P. aeruginosa. While all TOB-DEF conjugates were inactive against P. aeruginosa, the TOB-DEF conjugates strongly synergized with outer-membrane-impermeable antibiotics, such as novobiocin and rifampicin. Among the three TOB-DEF conjugates, 1c containing a C12 tether showed a remarkable and selective potentiating effect to improve the susceptibility of multidrug-resistant P. aeruginosa isolates to tetracyclines when compared with other antibiotics. However, the antibacterial activity and antibiotic-potentiating effect of the optimized conjugate was not enhanced under iron-depleted conditions, indicating that the function of the antibiotic potentiator is not affected by the Fe3+ concentration.

Biofilm Formation and Antimicrobial Susceptibility Pattern of <i>Staphylococcus aureus</i> 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.
 Objective: This study investigated the biofilm formation and antimicrobial susceptibility pattern of Staphylococcus aureus from two healthcare facilities in Zaria.
 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.
 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%).
 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.

Antibiotic sensitivity pattern of coagulase negative staphylococci in a tertiary care hospital of Southern Rajasthan

Coagulase negative staphylococci have been recognized as one of the important cause of hospital acquired infections in recent past. It has become difficult to manage these infections due to emergence of multidrug resistance to them. The aim of this study was to determine antibiotic sensitivity trend of all Coagulase negative Staphylococci isolates using modified Kirby- Bauer disk diffusion technique. To assess the antibiotic sensitivity for coagulase negative staphylococci, Kirby-Bauer disc diffusion method on Muller-Hinton agar was used. The study findings were interpreted on the basis of CLSI standards. All coagulase negative staphylococci isolates were given a predetermined panel of antibiotics. Methicillin-resistant coagulase negative staphylococci were identified using Cefoxitin disk. The sensitivity to Linezolid, Vancomycin and Rifampicin was found in all 500 isolates of coagulase negative staphylococci in our study. However, they were resistant to Penicillin G (65%), Cefoxitin (56%), Ciprofloxacin (57%), Levofloxacin (32%), Gentamicin (21%), Erythromycin (67%), Clindamycin (60%), Cotrimoxazole (51%) Tetracycline (9%). As CoNS have emerged as an important agent of hospital acquired infections, hence there is need of identification, speciation and resistance pattern of isolates for better management of patients.

Developing home cleaning intervention through community engagement to reduce infections and antimicrobial resistance in Ghanaian homes

Globally Antimicrobial Resistance (AMR) constitutes a health crisis, particularly in developing countries, where infectious disease are commonly fatal. There is clear evidence for microbial exposure and infection transmission within the home. Personal and environmental hygiene are the best ways of reducing household infections thus decreasing the need for antibiotics and consequently diminishing AMR. Despite this being an obvious step, research efforts to understand the home environment and its impact on AMR, cleaning and possible interventions on household cleaning are limited. We combined design and microbiology methods in an innovative mixed-method approach. A traditional survey design (n = 240), a design ethnography (n = 12), a co-design workshop and a pre-intervention microbiological dust sample analysis was undertaken to provide insights for codesign workshops in which new cleaning practices might be developed to minimise any AMR bacteria present in the household environments located in the Greater Accra Region of Ghana. Microbiological analysis of household dust showed that 36.6% of bacterial isolates detected were found to carry at least one resistance to the panel of antibiotics tested. Four scenarios were generated from an economic segmentation of the survey data. 50 ethnographic insights were ‘presented’ and descriptions of 12 bacteria species that showed resistance to one or more antibiotics (representing 176 bacterial isolates that showed resistance to one or more antibiotics found in the dust samples) were presented to the participants in a codesign workshop. An intervention, a new regime of cleaning practices agreed through the co-design workshop and practiced for thirty days, was made in (n = 7) households. The high prevalence of multidrug resistance observed in this study indicate the need for antibiotics surveillance program, not only in hospital settings but also in the household environment. There is, thus, an urgent need for targeting of interventions at the household level. Activating knowledge through community engagement in the research helps in increasing public perception and breaking down the scientist-public barrier.