Beta-lactam Beta-lactamase Inhibitors Research Articles

Predicting early appropriate therapy for patients infected by carbapenem-resistant Gram-negative pathogens in intensive care units in Italy

BackgroundAntibiotic resistance among Gram-negative bacteria in intensive care units (ICUs) is linked with high morbidity and mortality in patients. In this study, we estimated the therapeutic coverage of various antibiotics, focusing on cefiderocol and comparators, administered empirically against an infection of unknown origin in the ICU.MethodsIn the ARTEMIS surveillance study, susceptibilities of 624 Italian Gram-negative isolates to amikacin, aztreonam-avibactam, cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, colistin, imipenem-relebactam, meropenem, and meropenem-vaborbactam were tested by broth microdilution, and results were interpreted by European Committee on Antimicrobial Susceptibility Testing breakpoints. The susceptibility rates from the ARTEMIS study were extrapolated to Gram-negative isolates obtained from 5,774 patients in Italian ICUs in 2021. The sum of the predicted susceptibilities of individual pathogens represented the overall likelihood of in vitro activity of each antibiotic as early targeted therapy for ICU patients.ResultsA total of 624 Italian Gram-negative isolates included 206 Pseudomonas aeruginosa, 138 Acinetobacter baumannii, 187 Klebsiella pneumoniae, and 93 Escherichia coli. Against A. baumannii, K. pneumoniae, P. aeruginosa, and E. coli, the overall susceptibility rates for cefiderocol were 87.7%, 96.8%, 99%, and 100%, respectively; and for comparator agents, 8.7–96.4%, 25.7–100%, 73.3–100%, and 89.2–100%, respectively. Among the subset of meropenem-resistant isolates, susceptibility rates of A. baumannii, K. pneumoniae, and P. aeruginosa to cefiderocol were 86.4%, 96.2% and 100%, respectively. Corresponding susceptibility rates to comparator agents were 0–96.8%, 0–100%, and 6.4–100%, respectively. There were no meropenem-resistant isolates of E. coli. The extrapolation of data to isolates from Italian ICUs showed that the highest likelihood of therapeutic coverage, both overall and among meropenem-resistant isolates, was reported for colistin (96.8% and 72.2%, respectively) and cefiderocol (95.7% and 71.4%, respectively). All other antibiotics were associated with a likelihood below 73% overall and between 0% and 41.4% for meropenem-resistant isolates.ConclusionsBased on confirmed susceptibility rates and reported ICU prevalence of multiple Gram-negative species, cefiderocol showed a higher predicted therapeutic coverage and utility in ICUs compared with comparator beta-lactam–beta-lactamase inhibitor antibiotics. Cefiderocol may be a promising early treatment option for patients at high risk of carbapenem-resistant Gram-negative bacterial infections in the ICU.

Comparison of beta-lactam/ beta-lactamase inhibitors with carbapenem for urinary bacteremia caused by ceftriaxone resistant Escherichia coli and klebsiella species

Background: The debate, whether to treat ceftriaxone resistant (CROr) gram negative urinary tract infection with bacteremia (bUTI) with Beta-lactam/beta lactamase inhibitors (BL/BLI) or Carbapenem is going on. Carbapenem are expensive in our part of the world. Our aim was to see the efficacy of BL/BLI in the treatment of bUTI caused by CROr Escherichia coli (E-coli) or Klebsiella species (spp.) To compare microbiological clearance, clinical failure, new bacteremia and mortality between patients with bUTI who receive BL/BLI or Carbapenem. Material and Methods: A retrospective chart review was done at a tertiary care hospital of kidney diseases from October 2021 till June 2022. We included all adult patients with bUTI caused by CROr E-coli or Klebsiella spp, and they were excluded if bacteremia with no clear source or received antibiotics other than BL/BLI or carbapenems or received for less than 48 hours duration. Demographic characteristics, comorbidities, and clinical outcome were compared between BL/BLI and carbapenem groups. Results: A total of 41 files were reviewed. The demographics, risk factors and clinical features were comparable. We did not find statistically significant difference in microbiological clearance, clinical failure, and mortality between BL/BLI and Carbapenem groups. Conclusion: BL/BLI combinations are as efficacious as Carbapenems in CROr bUTI in terms of microbiological clearance. The clinical success and mortality were same in both groups. Keywords: bUTI, Klebsiella spp, Carbapenems, BL/BLI, Mortality, Disease severity, Microbiological clearance.

The Prevalence of Multidrug-Resistant Enterobacteriaceae among Neonates in Kuwait.

Increasing numbers of neonates with serious bacterial infections, due to resistant bacteria, are associated with considerable morbidity and mortality rates. The aim of this study was to evaluate the prevalence of drug-resistant Enterobacteriaceae in the neonatal population and their mothers in Farwaniya Hospital in Kuwait and to determine the basis of resistance. Rectal screening swabs were taken from 242 mothers and 242 neonates in labor rooms and wards. Identification and sensitivity testing were performed using the VITEK® 2 system. Each isolate flagged with any resistance was subjected to the E-test susceptibility method. The detection of resistance genes was performed by PCR, and the Sanger sequencing method was used to identify mutations. Among 168 samples tested by the E-test method, no MDR Enterobacteriaceae were detected among the neonates, while 12 (13.6%) isolates from the mothers' samples were MDR. ESBL, aminoglycosides, fluoroquinolones, and folate pathway inhibitor resistance genes were detected, while beta-lactam-beta-lactamase inhibitor combinations, carbapenems, and tigecycline resistance genes were not. Our results showed that the prevalence of antibiotic resistance in Enterobacteriaceae obtained from neonates in Kuwait is low, and this is encouraging. Furthermore, it is possible to conclude that neonates are acquiring resistance mostly from the environment and after birth but not from their mothers.

1805. Safety Outcomes Following Beta-Lactam use in Patients with a Documented Beta-Lactam Allergy

Abstract Background Management of bacterial infections typically consist of beta-lactam antibiotics. Individuals with histories of beta-lactam allergy are more likely to receive alternative broad-spectrum antibiotics which may be less efficacious or lead to increased adverse events. Patients can be prescribed full doses of structurally non-related beta-lactam antibiotics due to the low similarity of side chains between these medications and penicillin, and the low incidence of penicillin allergies being true allergies. Nevertheless, there is a lack of data regarding safety outcomes in patients who are treated with a beta lactam with a documented allergy. Methods This was a single-center retrospective observational study of patients with a documented beta-lactam allergy who received at least one dose of any beta-lactam antimicrobial excluding aztreonam from SUNY Downstate Health Sciences University between January 2015 – October 2021. Electronic medical records were reviewed for relevant study data. The primary outcome was the incidence of allergic reaction on full dose beta lactam with a documented allergy in the medical record. Results Baseline characteristics are summarized in Table 1. Two patients experienced a suspected allergic reaction while on beta-lactam therapy. Anaphylaxis was not reported and pharmacologic rescue agents were not required for each case. The antimicrobial agent was changed after the reaction was noted in both cases. Conclusion Patients who were administered beta-lactam antimicrobials with beta-lactam allergy had low rates of allergic reaction. The rate of allergic reactions observed is similar to the incidence of allergy in patients without documented allergies reported in the literature. Administration of beta-lactams with dissimilar side chains such as beta-lactam beta-lactamase inhibitors and third and fourth generation cephalosporins were safely administered to patients with a documented allergy. Disclosures All Authors: No reported disclosures.

Control of Healthcare-Associated Carbapenem-Resistant Acinetobacter baumannii by Enhancement of Infection Control Measures.

Antimicrobial stewardship and infection control measures are equally important in the control of antimicrobial-resistant organisms. We conducted a retrospective analysis of the incidence rate of hospital-onset carbapenem-resistant Acinetobacter baumannii (CRAB) infection (per 1000 patient days) in the Queen Mary Hospital, a 1700-bed, university-affiliated teaching hospital, from period 1 (1 January 2007 to 31 December 2013) to period 2 (1 January 2014 to 31 December 2019), where enhanced infection control measures, including directly observed hand hygiene before meal and medication rounds to conscious patients, and the priority use of single room isolation, were implemented during period 2. This study aimed to investigate the association between enhanced infection control measures and changes in the trend in the incidence rate of hospital-onset CRAB infection. Antimicrobial consumption (defined daily dose per 1000 patient days) was monitored. Interrupted time series, in particular segmented Poisson regression, was used. The hospital-onset CRAB infection increased by 21.3% per year [relative risk (RR): 1.213, 95% confidence interval (CI): 1.162–1.266, p < 0.001], whereas the consumption of the extended spectrum betalactam-betalactamase inhibitor (BLBI) combination and cephalosporins increased by 11.2% per year (RR: 1.112, 95% CI: 1.102–1.122, p < 0.001) and 4.2% per year (RR: 1.042, 95% CI: 1.028–1.056, p < 0.001), respectively, in period 1. With enhanced infection control measures, the hospital-onset CRAB infection decreased by 9.8% per year (RR: 0.902, 95% CI: 0.854–0.953, p < 0.001), whereas the consumption of the extended spectrum BLBI combination and cephalosporins increased by 3.8% per year (RR: 1.038, 95% CI: 1.033–1.044, p < 0.001) and 7.6% per year (RR: 1.076, 95% CI: 1.056–1.097, p < 0.001), respectively, in period 2. The consumption of carbapenems increased by 8.4% per year (RR: 1.84, 95% CI: 1.073–1.094, p < 0.001) in both period 1 and period 2. The control of healthcare-associated CRAB could be achieved by infection control measures with an emphasis on directly observed hand hygiene, despite an increasing trend of antimicrobial consumption.

PYOPERITONEUM SECONDARY TO PYOMETRA RUPTURE IN A CARCINOMA CERVIX PATIENT DUE TO ACTINOMYCES TURICENSIS AND PEPTOSTREPTOCOCCUS ANAEROBIUS : A CASE REPORT

We present a rare case of Pyoperitoneum secondary to Pyometra rupture in a carcinoma cervix patient due to dual pathogens- Actinomyces turicensis and Peptostreptococcus anaerobius. Escherichia coli, Enterococcus species, Bacteroides fragilis and Peptostreptococcus species are among the most common organisms isolated from cases of Pyometra. Though Actinomyces turicensis, a Gram positive bacilli belong to the genus Actinomycetes can be part of the normal microbiome of the genital tract, it has been described as a potential pathogen in genital, skin and soft tissue, urinary tract infections and even bacteraemia. The patient responded well to Metronidazole and beta lactam-beta lactamase inhibitor combinations. Hence the pathogenic role of these pathogens should not be ignored especially in patients who are immunocompromised.

Widespread emergence of OmpK36 loop 3 insertions among multidrug-resistant clones of Klebsiella pneumoniae.

Mutations in outer membrane porins act in synergy with carbapenemase enzymes to increase carbapenem resistance in the important nosocomial pathogen, Klebsiella pneumoniae (KP). A key example is a di-amino acid insertion, Glycine-Aspartate (GD), in the extracellular loop 3 (L3) region of OmpK36 which constricts the pore and restricts entry of carbapenems into the bacterial cell. Here we combined genomic and experimental approaches to characterise the diversity, spread and impact of different L3 insertion types in OmpK36. We identified L3 insertions in 3588 (24.1%) of 14,888 KP genomes with an intact ompK36 gene from a global collection. GD insertions were most common, with a high concentration in the ST258/512 clone that has spread widely in Europe and the Americas. Aspartate (D) and Threonine-Aspartate (TD) insertions were prevalent in genomes from Asia, due in part to acquisitions by KP sequence types ST16 and ST231 and subsequent clonal expansions. By solving the crystal structures of novel OmpK36 variants, we found that the TD insertion causes a pore constriction of 41%, significantly greater than that achieved by GD (10%) or D (8%), resulting in the highest levels of resistance to selected antibiotics. We show that in the absence of antibiotics KP mutants harbouring these L3 insertions exhibit both an in vitro and in vivo competitive disadvantage relative to the isogenic parental strain expressing wild type OmpK36. We propose that this explains the reversion of GD and TD insertions observed at low frequency among KP genomes. Finally, we demonstrate that strains expressing L3 insertions remain susceptible to drugs targeting carbapenemase-producing KP, including novel beta lactam-beta lactamase inhibitor combinations. This study provides a contemporary global view of OmpK36-mediated resistance mechanisms in KP, integrating surveillance and experimental data to guide treatment and drug development strategies.

Pharmacokinetic evaluation of cefiderocol for the treatment of multidrug resistant Gram-negative infections

ABSTRACT Introduction Cefiderocol is a siderophore cephalosporin antibiotic and first of its kind approved by the Food and Drug Administration for the treatment of complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) in patients 18 years or older caused by susceptible organisms. Cefiderocol’s unique mechanism of iron chelation improves Gram-negative membrane penetration as the bacteria’s iron uptake mechanism recognizes the chelated iron antibiotic and iron for entry. This also allows for the evasion of cefiderocol from cell entry-related resistance mechanisms. Areas covered This review covers the mechanism of action, resistance mechanisms, pharmacokinetics in various patient populations, and pharmacodynamics. Relevant literature evaluating efficacy and safety are discussed. Expert opinion Limited treatment options are available for the treatment of carbapenem-resistantorganisms. Clinical trials have demonstrated that cefiderocol is no worse than alternative treatment options for cUTIs and HABP/VABP, but more data are currently available to support the use of beta-lactam beta-lactamase inhibitor agents, where susceptible. Mortality differences demonstrated in patients with pneumonia and bloodstream infections must further be explored and logistical and practical considerations regarding susceptibility testing and use as monotherapy vs. combination therapy must be considered prior to confidently recommending cefiderocol for regular use in systemic infections.

New evidence for managing Gram-negative bloodstream infections.

Gram-negative bloodstream infections (GNBSI) are common and carry considerable mortality. Treatment is complicated by increasing antimicrobial resistance, posing a challenge for timely appropriate antibiotics and limiting the choices of effective definitive therapy. The present review aims to summarize recent studies addressing the management of GNBSI. New rapid diagnostic tests (RDT) for pathogen identification and antibiotic susceptibility are associated with improved antimicrobial stewardship and reduced length of stay. No mortality benefit or patient-related outcomes are reported. Data regarding the use of new beta-lactam beta-lactamase inhibitors (BLBLIs) for treating multidrug resistance Gram-negative bacteria is supportive, though questions regarding combinations, optimal dosing, mode of administration, and resistance emergence remain to be clarified. Current data regarding cefiderocol necessitates further studies in order to support its use in GNBSI. Shortened (≤7 days) duration of therapy and early oral step down for GNBSI are supported by the literature. The role of repeated blood cultures should be further defined. RDTs should be implemented to improve antibiotic stewardship. Clinical implications on patient-related outcomes should be evaluated. New BLBLIs show promise in the treatment of GNBSI. Additional data are needed regarding the use of cefiderocol. Antibiotic therapy should be shortened and early oral step down should be considered.

1621. Novel Beta-lactam Beta-lactamase Inhibitors Against Alternative Antibiotics for the Treatment of Complicated Urinary Tract Infections and Pyelonephritis Caused by Carbapenem-resistant Enterobacterales

BackgroundThere is little data on the comparative efficacy or safety of carbapenem-resistant Enterobacterales (CRE)-targeted beta-lactam beta-lactamase inhibitors (BL-BLI), including ceftazidime/avibactam (CZA) and meropenem/vaborbactam (MVB), versus alternative antibiotics for the treatment of CRE complicated urinary tract infections/acute pyelonephritis (cUTI/AP). The objective of this study was to evaluate rates of clinical failure in patients with CRE cUTI/AP treated with CRE-targeted BL-BLI vs. alternative regimens.MethodsThis was a multicenter, retrospective cohort study of adults admitted with a CRE cUTI/AP treated with CRE-active antibiotic(s), including combination therapy, for at least 48 hours between January 2012 and June 2019. Exclusion criteria included CRE colonization, non-urinary source co-infection, non-Enterobacterales cUTI/AP, or mortality within 48 hours of index culture. The primary outcome was clinical failure, defined as continued symptoms or recurrence at 30 days from index culture. Secondary outcomes included 90-day recurrence and 30-day readmission. Safety outcomes included treatment-limiting adverse effects, non-treatment limiting nephrotoxicity, and C. difficile infection.ResultsA total of 47 patients were included (BL-BLI, n=16; alternative, n=31). Alternative regimens contained aminoglycosides, carbapenems, polymyxins, and tigecycline and utilized combination therapy more often (32.3% vs. 6.3%, p=0.046). Clinical failure occurred in 12.5% of patients in the BL-BLI group vs. 38.7% in the alternative group (p=0.063). Higher rates of 90-day recurrence (25.8% vs. 18.8%) and 30-day readmissions (51.6% vs. 31.3%) occurred in the alternative group vs. the BL-BLI group but were not statistically significant (Table 2). There were clinically significant rates of nephrotoxicity in the alternative group (45.2%) compared to the BL-BLI group (18.8%), contributing largely to the difference in treatment-limiting adverse effects (29% vs. 0%, p=0.017).Table 1: Antibiotic Data Table 2: Efficacy Outcomes Table 3: Safety Outcomes ConclusionIn this retrospective study, no difference in clinical failure resulted among groups; however, there was significantly more treatment-limiting adverse effects in the alternative group compared to the BL-BLI-based regimens, driven by nephrotoxicity.Disclosures All Authors: No reported disclosures

Cost-Effectiveness Analysis of New Beta-Lactam Beta-Lactamase Inhibitor Antibiotics Versus Colistin for the Treatment of Carbapenem-Resistant Infections.

Introduction: Carbapenem-resistant organisms (CROs) present a serious public health problem. Limited treatment options has led to increased use of colistin and polymyxin. Since 2014, the US Food and Drug Administration approved 4 new beta-lactam beta-lactamase inhibitor (BLBLI) combination antibiotics with activity against CROs. These new antibiotics have been shown to be more effective and less toxic than colistin and polymyxin but are considerably more expensive. This study evaluated the cost-effectiveness of the new BLBLIs versus colistin-based therapy for the treatment of CROs. Methods: A decision-tree microsimulation model was used to evaluate the cost effectiveness of the new BLBLIs versus colistin-based therapy for the treatment of CROs. Treatment groups differed in risk of mortality and risk of an acute kidney injury (AKI). The relative risk of mortality was determined by creating a meta-analysis comparing new BLBLIs to colistin. Cost inputs included medication costs and the cost to treat an AKI. The primary outcomes include quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). Model inputs included: clinical outcomes and adverse events (30-day mortality and AKI); cost of treatment and adverse drug events; and health utilities. A 3% discount was applied for outcomes. A lifetime horizon was used from the perspective of the US healthcare system with a willingness-to-pay (WTP) threshold of $100 000. A sensitivity analysis was done to incorporate uncertainty. Results: The meta-analysis found the treatment with a new BLBLI was associated with a 50% decrease in the relative risk of 30-day mortality compared to colistin (RR 0.47, 95% CI 0.25-0.88). Treatment with a new BLBLI cost $16 200 and produced 11.5 QALYs, on average. The average colistin based regimen cost $3500 and produced 8.3 QALYs. The new BLBLIs were determined to be cost-effective with an ICER of $3900 per QALY gained. Treatment with a BLBLI remained cost-effective under all uncertainty scenarios tested. Conclusion: New BLBLIs are cost-effective compared to colistin for the treatment of CROs and are associated with improved mortality and fewer AKI events. The use of colistin should be reserved for cases where new BLBLIs are not available or there is documented resistance to these new antibiotics.

Ceftazidime/avibactam and ceftolozane/tazobactam for the treatment of extensively drug-resistant Pseudomonas aeruginosa post-neurosurgical infections: three cases and a review of the literature.

PurposePost-neurosurgical infection caused by extensively drug resistant Pseudomonas aeruginosa (XDR-PA) are becoming a matter of great concern due to limited therapeutic options. Although not approved for these indications, the new BetaLactam-BetaLactamase Inhibitor combinations (BLBLIs) could represent a valid salvage treatment. We describe one nosocomial meningitis and two cervical osteomyelitis due to an XDR-PA who were treated with ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T) and review the literature.MethodsThe first and the third patients developed an osteomyelitis following cervical stabilization surgery due to an XDR-PA. Although the first patient started treatment with a high dose of C/T, resistance to C/T occurred, so therapy was switched to CZA plus aztreonam. The third patient switched to aztreonam plus CZA due to development of acute kidney injury during therapy with colistin. The second patient had an XDR-PA meningitis following the insertion of an external ventricular catheter and he was treated with C/T plus meropenem and amikacin.ResultsAll three cases reported were successfully conservatively treated thanks to the use of the new BLBLIs with different combinations. Only few experiences demonstrated an equally favorable outcome: one patient treated with C/T plus fosfomycin for otogenic meningitis caused by an XDR-PA and another case of XDR-PA post-surgical meningitis with CZA in combination with colistin. Finally, the combination of CZA plus aztreonam has proven to be effective on XDR-PA only in limited mostly in vitro studies.ConclusionThese recently developed antibiotics, C/T and CZA are promising and complementary therapy options against post-neurosurgical hard-to-treat P. aeruginosa infections. Further prospective real-life studies are required to validate these findings in this special setting.

Ceftazidime-Avibactam Combination Therapy Compared to Ceftazidime-Avibactam Monotherapy for the Treatment of Severe Infections Due to Carbapenem-Resistant Pathogens: A Systematic Review and Network Meta-Analysis.

Ceftazidime-avibactam (CZA) is a novel beta-lactam beta-lactamase inhibitor combination approved for the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and for hospital-acquired/ventilator-associated pneumonia. The aim of this systematic review (PROSPERO registration number: CRD42019128927) was to evaluate the effectiveness of CZA combination therapy versus CZA monotherapy in the treatment of severe infections. The databases included in the search, until 12 February 2020, were MEDLINE by PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials. We included both randomized controlled trials (RCTs) and non-randomized studies published in peer-reviewed journals and in the English language. The primary outcome was all-cause mortality (longest follow-up) evaluated in patients with the diagnosis of infection with at least one pathogen; secondary outcomes were clinical and microbiological improvement/cure. Thirteen studies were included in the qualitative synthesis: 7 RCTs and 6 retrospective studies All the six retrospective studies identified carbapenamase-producing Enterobacteriaceae (CRE) as the cause of infection and for this reason were included in the network meta-analysis (NMA); the quality of the studies, assessed using the New Castle-Ottawa Scale, was moderate-high. In all the six retrospective studies included in the NMA, CZA was used in large part for off-label indications (mostly blood stream infections: 80–100% of patients included). No difference in mortality rate was observed in patients undergoing CZA combination therapy compared to CZA monotherapy [n = 503 patients, direct evidence OR: 0.96, 95% CI: 0.65–1.41].

Predominance of Multidrug-Resistant Gram-Negative Organisms as Cause of Surgical Site Infections at a Private Tertiary Care Hospital in Mumbai, India

AbstractBackground: This study aims to study the incidence, microbial aetiology and antimicrobial susceptibility of surgical site infections (SSIs) at a private tertiary care hospital in Mumbai, India, and compare it with previously published data from the same institute as well as literature. Methods: This is a prospective observational study done over 6 years (January 2013–December 2018) at a 750-bed private multi-specialty hospital in Mumbai, India, among all patients undergoing clean and clean-contaminated surgeries. Standard guidelines for preventing, diagnosing and classifying SSIs were followed. The incidence rates of SSI (overall and specialty specific), microbial aetiology and antibiotic susceptibility of SSI were calculated and expressed as percentages. Results: A total of 55,553 patients underwent clean and clean-contaminated surgeries during the study period. The overall SSI rate was 1.0% (555 cases). The SSI rate in clean surgeries was 0.97% and in clean-contaminated surgeries was 1.03%. Sixty-five per cent of SSIs were due to Gram-negative bacilli, 30% were due to Gram-positive cocci and 4% were due to Candida. Klebsiella pneumoniae (19%), Escherichia coli (17%), Pseudomonas aeruginosa (13%), Staphylococcus aureus (12%) and Enterococcus (10%) were the top five organisms. The overall susceptibility rate of the Gram-negative isolates to beta-lactam–beta-lactamase inhibitor combinations was 60% and carbapenems was 73%. The prevalence of methicillin resistance in S. aureus was 44% and coagulase-negative Staphylococcus was 84%. The crude mortality rate was 1%. Conclusions: Although the SSI rate is comparable to established international benchmarks, the predominance of multidrug-resistant Gram-negative organisms is a matter of serious concern.

A retrospective analysis of antibiogram on urinary isolates in a tertiary care hospital, Trivandrum, India

Background: Antimicrobial resistance among bacterial strains is an emerging problem. Urinary tract infections are one of the most common bacterial infections in humans both in the hospital and the community settings. Gram-negative bacilli are the common pathogens isolated in urine. These uropathogens have developed resistance to commonly prescribed antimicrobial agents. This severely limits the effective empirical treatment options. Objective of this study was to determine the prevalence and antibiotic susceptibility patterns of bacterial uropathogens isolated from patients attending a tertiary care hospital Trivandrum.Methods: Urine samples received for culture in the laboratory between 6 month periods was cultured in MacConkey agar and blood agar plates. The growth from urine cultures was processed for identification and antibiotic susceptibility as per standard methods. The details of urinary pathogens grown from urine samples and their Antibiogram profile were collected from the records.Results: Out of 924 specimens investigated for significant bacteriuria, 226 shows positive cultures. E.coli and Klebsiella were the predominant pathogens isolated. Antibiotics like 3rd generation cephalosporins, fluoroquinolones, and cotrimoxazole are the usual empirical treatment options, these organisms have developed resistance towards the latter which might make the empirical therapy less effective.Conclusions: Gram-negative bacilli were the predominant pathogens isolated and many were resistant to the commonly prescribed antibiotics. Routine surveillance and monitoring studies need to be constantly conducted to update clinicians on the prevalent pathogens for the rational and empirical treatment of bacteriuria. Beta-lactam beta-lactamase inhibitors, aminoglycosides, carbapenem, and nitrofurantoin showed low resistance so they should be considered as empirical treatment options.

Nasal carriage of methicillin-resistant Staphylococcus aureus among health-care workers at a tertiary care hospital in Northern India

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to all beta-lactam antibiotics, including penicillins, cephalosporins, carbapenems, and betalactamase inhibitors. MRSA remains a public health problem globally. MRSA infection increases morbidity, risk of mortality, increased financial burden, and loss of productivity. A major source of MRSA in the hospital environment can be asymptomatically colonized health-care workers (HCWs). Objectives: The aim of the study is to screen nasal swabs collected from HCWs of our hospital for colonization with S. aureus and detect methicillin resistance among them. Materials and Methods: In this cross-sectional study, consenting HCWs were consecutively enrolled. Nasal swabs were collected aseptically from study participants and processed using standard microbiological protocols for the recovery of S. aureus and MRSA. Methicillin resistance was detected by cefoxitin disc diffusion method according to the CLSI guidelines. Results: Out of a total of 184 HCWs studied, the prevalence of S. aureus carriage in anterior nares was 14.6%. The overall MRSA prevalence was 3.8%. Highest carriage rates for MRSA were found in laboratory technicians (7.1%) followed by nursing staff (4.4%). The ophthalmology department had the highest MRSA carriage rate of 22%. Conclusions: Our findings demonstrate that nasal carriage of MRSA among HCWs is relatively low in this study compared to other Indian studies done in tertiary care centres. Further studies are needed to evaluate the incidence of infections due to MRSA in this population.

Treatment Modalities and Antimicrobial Stewardship Initiatives in the Management of Intra-Abdominal Infections.

Antimicrobial stewardship programs (ASPs) focus on improving the utilization of broad spectrum antibiotics to decrease the incidence of multidrug-resistant Gram positive and Gram negative pathogens. Hospital admission for both medical and surgical intra-abdominal infections (IAIs) commonly results in the empiric use of broad spectrum antibiotics such as fluoroquinolones, beta-lactam beta-lactamase inhibitors, and carbapenems that can select for resistant organisms. This review will discuss the management of uncomplicated and complicated IAIs as well as highlight stewardship initiatives focusing on the proper use of broad spectrum antibiotics.

Incidence and Antibiotic Susceptibility Profile of Staphylococcus aureus on Door Handles in Ahmadu Bello University, Zaria

Pathogenic microorganisms implicated in most diseases are transferable through contact with infected persons or objects. In this study, door handles in the Faculty of Pharmaceutical Sciences and Amina female hostel in Ahmadu Bello University, Zaria, Nigeria were evaluated for the presence of Staphylococcus aureus and their antibiotics susceptibility profile was tested, using standard microbiological methods. The results showed that out of the 143 door handles sampled (Amina female hostel = 89, Pharmacy main block = 40, Pharmacy old block = 14), the incidence of Staphylococcus aureus was 50.7%(34) [with highest occurrence in Amina female hostel (35.8%), followed by Pharmacy main block (8.9%) and Pharmacy old block (6.0%)], E. coli was observed to be the second most common organism (9%) followed by Shigella dysentery 7.5%, while Salmonella typhi, Seretia spp. and Pseudomonas aeruginosa were both 6% respectively. The antibiotic susceptibility profile of the isolates showed that they were 100% susceptible to Ciprofloxacin, Erythromycin and Tetracycline, 97% susceptible to Mupirocin, and Cotrimoxazole, and 92% to Pefloxacin and Oxacillin. Their levels of resistance to these antibiotics were very low (3% resistance to Mupirocin and Cotrimoxazole, 8% to Pefloxacin and Oxacillin), while their resistances to Amoxicillin, Cefuroxin sodium and Cefotaxime were very high (100%). An evaluation of the pattern of resistance of the isolates showed that 76.5% of the isolates had MAR index of ≤0.4 while 70.6% of the isolates were multidrug resistant; exhibiting resistance to some commonly used Fluoroquinolone, Cephalosporine (CEP), and Betalactam/Betalactamase inhibitors (BET) groups of antibiotics (73.5%). The high incidence of Staphylococcus aureus in this study suggests poor hygiene among students, and the possibility of transferring pathogenic Staphylococcus aureus through door handles in a densely populated environ during disease outbreak is probable. To curb the spread of pathogenic and resistant Staph. aureus, this study suggests that door handles in A.B.U, Zaria should be replaced with silver coated surfaces with antimicrobial properties, and frequent use of disinfectant/hand sanitizer is recommended. Also proper periodic antibiotic surveillance should be encouraged to have referable documentaries in disease outbreak.

In vitro antibacterial activity of beta lactam-beta lactamase inhibitor combinations against clinical isolates of Acinetobacter spp.

In vitro antibacterial activity of beta lactam-beta lactamase inhibitor combinations against clinical isolates of Acinetobacter spp.

In vitro antibacterial activity of beta lactam-beta lactamase inhibitor combinations against clinical Isolates of acinetobacter

In vitro antibacterial activity of beta lactam-beta lactamase inhibitor combinations against clinical Isolates of acinetobacter