Antibiotic Treatment Regimens Research Articles

Epidemiological and Clinical Insights into Acinetobacter baumannii: A Six-Year Study on Age, Antibiotics, and Specimens.

This six-year retrospective study provides an in-depth analysis of the epidemiological and clinical patterns associated with Acinetobacter baumannii (A. baumannii) infections, focusing on age distribution, antibiotic resistance profiles, and specimen types. The research examines the incidence and characteristics of both non-Multi-Drug Resistant (non-MDR) and Multi-Drug Resistant (MDR) A. baumannii strains by reviewing patient records from January 2016 to December 2022. Through a statistical analysis, the study highlights the incidence rates across diverse age groups and explores the impact of antibiotic treatment regimens on infection outcomes. Additionally, it identifies the primary clinical specimen types for each strain, noting an association between non-MDR A. baumannii and midstream urine samples, while MDR A. baumannii strains were more frequently found in respiratory, wound, peripheral, and central line swaps/specimens. The results indicate that in 2016, non-MDR A. baumannii infections were notably more frequent compared to MDR A. baumannii cases. However, a significant shift occurred in 2021 and 2022, with a marked decrease in non-MDR A. baumannii cases and an increase in MDR A. baumannii infections. Antibiotic susceptibility testing revealed that non-MDR strains were commonly tested against cefazolin, ceftazidime, ciprofloxacin, gentamicin, nitrofurantoin, oxacillin, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole. In contrast, MDR strains were frequently tested against amikacin, cefepime, colistin, meropenem, imipenem, and tigecycline. This study enhances the understanding of A. baumannii clinical behaviour and resistance patterns, offering valuable insights to support future research and inform strategies for infectious disease management and control.

Comparative safety of different antibiotic regimens for the treatment of outpatient community-acquired pneumonia among otherwise healthy adults.

Evidence is limited about the comparative safety of antibiotic regimens for treatment of community-acquired pneumonia (CAP). We compared the risk of adverse drug events (ADEs) associated with antibiotic regimens for CAP treatment among otherwise healthy, non-elderly adults. We conducted an active comparator new-user cohort study (2007-2019) of commercially-insured adults 18-64 years diagnosed with outpatient CAP, evaluated via chest x-ray, and dispensed a same-day CAP-related oral antibiotic regimen. ADE follow-up duration ranged from 2-90 days (e.g., renal failure [14 days]). We estimated risk differences [RD] per 100 treatment episodes and risk ratios using propensity score weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes. Of 145,137 otherwise healthy CAP patients without comorbidities, 52% received narrow-spectrum regimens (44% macrolide, 8% doxycycline) and 48% received broad-spectrum regimens (39% fluoroquinolone, 7% β-lactam, 3% β-lactam + macrolide). Compared to macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (e.g., β-lactam: nausea/vomiting/abdominal pain [RD per 100, 0.32; 95% CI, 0.10-0.57]; non-Clostridioides difficile diarrhea [RD per 100, 0.46; 95% CI, 0.25-0.68]; vulvovaginal candidiasis/vaginitis [RD per 100, 0.36; 95% CI, 0.09-0.69]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding. Broad-spectrum antibiotics were associated with increased risk of ADEs among otherwise healthy adults treated for CAP in the outpatient setting. Antimicrobial stewardship is needed to promote judicious use of broad-spectrum antibiotics and ultimately decrease antibiotic-related ADEs.

Application of the estimand framework for an emulated trial using reference based multiple imputation to investigate informative censoring

BackgroundThe ICH E9 (R1) addendum on Estimands and Sensitivity analysis in Clinical trials proposes a framework for the design and analysis of clinical trials aimed at improving clarity around the definition of the targeted treatment effect (the estimand) of a study.MethodsWe adopt the estimand framework in the context of a study using “trial emulation” to estimate the risk of pneumocystis pneumonia, an opportunistic disease contracted by people living with HIV and AIDS having a weakened immune system, when considering two antibiotic treatment regimes for stopping antibiotic prophylaxis treatment against this disease. A “while on treatment” strategy has been implemented for post-randomisation (intercurrent) events. We then perform a sensitivity analysis using reference based multiple imputation to model a scenario in which patients lost to follow-up stop taking prophylaxis.ResultsThe primary analysis indicated a protective effect for the new regime which used viral suppression as prophylaxis stopping criteria (hazard ratio (HR) 0.78, 95% confidence interval [0.69, 0.89], p < 0.001). For the sensitivity analysis, when we apply the “jump to off prophylaxis” approach, the hazard ratio is almost the same compared to that from the primary analysis (HR 0.80 [0.69, 0.95], p = 0.009). The sensitivity analysis confirmed that the new regime exhibits a clear improvement over the existing guidelines for PcP prophylaxis when those lost to follow-up “jump to off prophylaxis”.ConclusionsOur application using reference based multiple imputation demonstrates the method’s flexibility and simplicity for sensitivity analyses in the context of the estimand framework for (emulated) trials.

Bacterial Culture Results and Antibiograms in Chronic Rhinosinusitis Patients in Mekong Delta, Vietnam

Background The inappropriate use of antibiotics for chronic rhinosinusitis, exceeding established guidelines, is a growing concern in Vietnam. This practice is contributing to the emergence and spread of antibiotic-resistant bacteria. Objective This study aimed to evaluate the results of culture and antibiogram of bacteria on patients in the Mekong Delta, Vietnam, who were treated for chronic rhinosinusitis in 2022-2023. Methods It is a cross-sectional study, including 113 patients who came for treatment with a diagnosis of chronic rhinosinusitis at Can Tho University of Medicine and Pharmacy Hospital, Mekong Delta, Vietnam, from 2022-2023. The bacterial cultures were identified, and their antibiograms were performed in the Microbiology laboratory of Can Tho University of Medicine and Pharmacy. Statistical analysis was performed with SPSS version 20.0. Results The rate of bacterial growth was 97.35%. The cultured bacterial composition had 8 genera, 22 species, and 116 samples, of which 2 bacterial species were cultured, accounting for 5.45%. Antibiogram showed that Streptococcus pneumonia was resistant to cefaclor (83.33%), cefuroxime (100%), trimethoprim+ sulfamethoxazole (100%), and susceptible to chloramphenicol (100%) and vancomycin (100%). Streptococcus haemolyticus was resistant to amoxicillin+clavulanic acid (85.71%) and ampicillin (100%) and susceptible to linezolid (100%) and rifampin (100%). Streptococcus epidermidis was resistant to amoxicillin+clavulanic acid (82.35%), ampicillin (100%), penicillin (100%) and susceptible to linezolid (91.18%) and rifampin (88.24%). Streptococcus aureus was resistant to amoxicillin+clavulanic acid (95%) and ampicillin+sulbactam (90%), and susceptible to linezolid (90%) and synercid (95%). Pseudomonas aeruginosa was resistant to amikacin (100%), meropenem (100%) and tobramycin (90%). Conclusion This study offers some useful information to doctors in the Mekong Delta and across Vietnam. It can be used as a good orientation in choosing the most appropriate antibiotics for treating patients with chronic rhinosinusitis. It is important to be conscious of the current trend of the bacteriological profiles and to regulate the antibiotic treatment regime to improve the effectiveness and reduce antibiotic resistance rate.

Shorter versus longer duration antibiotic regimens for treatment of suspected neonatal sepsis.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the safety and effectiveness of shorter versus longer duration antibiotic regimens for the treatment of suspected neonatal sepsis.

Double trouble: an unusual case of Klebsiella pneumoniae invasive syndrome with liver abscess, gallbladder empyema and infective endocarditis

BackgroundKlebsiella pneumoniae invasive syndrome (KPIS) is characterized by primary pyogenic liver abscess associated with metastatic infections. Although rare, Klebsiella endocarditis carries a high mortality risk.Case presentationA 60-year-old lady with type II diabetes mellitus presented with fever, malaise, right hypochondriac pain and vomiting for two weeks. Ultrasound abdomen revealed a collection within liver, and distended gallbladder with echogenic debris within. 3 days after ultrasound guided pigtail drainage of gallbladder empyema, newly presence murmur detected. Pus, urine, and blood cultures obtained were positive for Klebsiella pneumonia. Echocardiogram exhibited oscillating mass attached to anterior mitral valve leaflet. After 6 weeks of intravenous ceftriaxone, follow-up echocardiogram and ultrasound showed complete resolution of mitral valve vegetation, hepatic and gallbladder collection.ConclusionConcomitant extrahepatic infective endocarditis (IE) should raise concerns in daily practice for patients with Klebsiella pneumoniae liver abscesses, despite the rarity of Klebsiella endocarditis. In the absence of diagnostic suspicion, antibiotic treatment regimens may be shortened, and adverse effects from IE infection may ensue.

Efficacy of Antibiotic Regimens for Meningitis in Young Infants Aged 0-59 Days: A Systematic Review.

Meningitis is associated with high mortality risk in young infants, yet the optimal treatment regimen is unclear. To systematically evaluate the efficacy of antibiotic regimens to treat meningitis in young infants aged 0 to 59 days on critical clinical outcomes. MEDLINE, Embase, CINAHL, WHO Global Index Medicus, and Cochrane Central Registry of Trials. We included randomized controlled trials (RCTs) of young infants with meningitis (population) comparing the efficacy of antibiotic regimens (interventions) with alternate regimens (control) on clinical outcomes. We extracted data on study characteristics and assessed risk of bias in duplicate. Grading of Recommendations Assessment, Development, and Evaluation was used to assess certainty of evidence. Of 1088 studies screened, only 2 RCTs were identified. They included 168 infants from 5 countries and were conducted between 1976 and 2015. Neither study compared current World Health Organization-recommended regimens. One multisite trial from 4 countries compared intrathecal gentamicin plus systemic ampicillin/gentamicin to systemic ampicillin/gentamicin and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or adverse events (no events in either trial arm). Another trial in India compared a 10-day versus 14-day course of antibiotics and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or other outcomes. Trial data on the efficacy of antibiotic regimens in young infant meningitis are scarce. Rigorous RCTs are needed to inform recommendations for optimal antibiotic regimens for meningitis treatment in this vulnerable population, particularly within the context of changing epidemiology and increasing antimicrobial resistance.

Shorter versus longer duration antibiotic regimens for treatment of culture-positive neonatal sepsis.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the safety and effectiveness of shorter versus longer duration antibiotic regimens for the treatment of culture-positive neonatal sepsis with or without meningitis.

Analysis of antibiotic regimens and outcomes in spinal brucellosis: insights from a retrospective cohort study in Makkah, Saudi Arabia.

Brucellosis is a zoonotic disease that is widely spread across the globe, with the number of cases increasing annually. Spinal brucellosis is known to affect about half of patients with brucellosis. Nevertheless, data on the optimal antibiotic regimens for spinal brucellosis are limited. Therefore, this study aims to compare antibiotic treatment regimens for spinal brucellosis at our center in Makkah, Saudi Arabia. This is a retrospective cohort study of an 11-year period from 2010 to 2021 conducted at a single center in Makkah, Saudi Arabia. All patients with spinal brucellosis were included. Patients were excluded if the duration of the received antibiotic regimen or follow-up was poorly documented. Data analysis was conducted using RStudio (R version 4.1.1). Categorical variables of each regimen used by the patients were presented as frequencies and percentages, while numerical variables were summarized using the median and interquartile range (IQR). A total of 35 patients were included; the median (IQR) age of the patients was 58.0 (48.0 to 63.0) years. The most frequently reported symptoms upon admission included low back pain (83.3%). The most frequently administered regimen was the combination of streptomycin + doxycycline + rifampicin (SDR) (20 patients, 55.6%), followed by the combination of streptomycin + rifampicin + trimethoprim/sulfamethoxazole (SRT) (eight patients, 22.2%). Overall, out of the total 35 patients who received first-line treatment, only six patients experienced therapy failure. Out of the total six patients who experienced first-line treatment failure with SDR (five patients, 83%) and SDT (one patient, 17%), surgery was indicated for three patients. Surgical intervention was deemed necessary in 12 patients (34%). Three patients chose not to undergo surgical intervention but still showed complete improvement upon completing the treatment duration. One patient experienced a postoperative complication, resulting in paraplegia. In this study, we found that among 35 patients, treatment failure was observed only in six patients who received triple therapy. In addition, surgical intervention was indicated in 12 patients; however, three patients refused surgery and improved ultimately after changing or extending the duration of the antibiotic regimen.

#784 Peritoneal dialysis-related infections by Kocuria kristinae: cases from a Mexican hospital

Abstract Background and Aims Kocuria species, gram-positive actinobacteria, are typically found in the environment, on human skin and as oral flora. These microorganisms are considered saprophytes and non-pathogenic. They rarely cause infections. Patients generally have some compromise due to underlying conditions, including solid tumors, hematologic malignancies, or metabolic disorders. There are few cases in the literature of peritoneal dialysis-associated peritonitis due to these germs. Reports of exit site infections or tunnel infections are even rarer or doesn't exist. Method Retrospective description of 4 cases of exit site and/or tunnel infections due to Kocuria kristinae over a 3-year period in a single center. Results Four cases of exit site infection were evaluated, with an average age of 63.2 ± 8.8 years. Half of the patients were diabetic. No patient had a history of peritoneal dialysis-related infection. The dialysis modality for all patients was CAPD (Continuous Ambulatory Peritoneal Dialysis). All patients presented symptoms of exit site infection, such as erythema and purulent discharge, but none of them had peritonitis. Three cases were treated with quinolones, and one received linezolid. One case received two antibiotic treatment regimens without an adequate response, and tunnel infection developed, required the removal of the dialysis catheter and a change in modality to HD (hemodialysis). Conclusion Exit site infections due to Kocuria are extremely rare. Despite the absence of specific management guidelines, the response to treatment is usually adequate. Due to the theoretical ability to produce biofilm, Kocuria infections should be considered a potential risk for recurrence and refractory disease. To our knowledge, there are no reports of exit site infections due to Kocuria.

Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.

Impact of Pseudomonas aeruginosa on resource utilization and costs in patients with exacerbated non-cystic fibrosis bronchiectasis

Aims Non‐cystic fibrosis bronchiectasis (NCFB) is a chronic progressive respiratory disorder occurring at a rate ranging from 4.2 to 278.1 cases per 100,000 persons, depending on age, in the United States. For many patients with NCFB, the presence of Pseudomonas aeruginosa (PA) makes treatment more complicated and typically has worse outcomes. Management of NCFB can be challenging, warranting a better understanding of the burden of illness for NCFB, treatments applied, healthcare resources used, and subsequent treatment costs. Comparing patients diagnosed with exacerbated NCFB, with or without PA on antibiotic utilization, treatments, and healthcare resources utilization and costs was the purpose of this study. Materials and methods This was a retrospective cohort study of commercial claims from IQVIA’s PharMetrics Plus database (January 1,2006–December 31, 2020). Study patients with a diagnosis of NCFB were stratified into two groups based on the presence or absence of PA, then followed to identify demographic characteristics, comorbid conditions, antibiotic treatment regimen prescribed, healthcare resources utilized, and costs of care. Results The results showed that patients with exacerbated NCFB who were PA+ had significantly more oral antibiotic fills per patient per year, more inpatient admissions with a longer length of stay, and more outpatient encounters than those who were PA−. For costs, PA+ patients also had significantly greater total healthcare costs per patient when compared to those who were PA−. Conclusion Exacerbated NCFB with PA+ was associated with increased antibiotic usage, greater resource utilization, and increased costs. The major contributor to the cost differences was the use of inpatient services. Treatment strategies aimed at reducing the need for inpatient treatment could lessen the disparities observed in patients with NCFB.

Bicyclomycin generates ROS and blocks cell division in Escherichia coli.

The role of reactive oxygen species (ROS) in the killing exerted by antibiotics on bacteria is debated. Evidence attributes part of toxicity of many antibiotics to their ability to generate ROS by interfering with cellular metabolism, but some studies dismiss the role of ROS. Bicyclomycin (BCM) is a broad-spectrum antibiotic that is the only known compound to inhibit E. coli transcription terminator factor Rho with no known other cellular targets. In the present study, we addressed this question by checking whether the induction of oxidative stress could explain the increased sensitivity to Bicyclomycin in the hns deleted strain even in Δkil background in E. coli. BCM evoked the generation of ROS in E. coli cells. BCM is known to cause the cell filamentation phenotype in E. coli. Performing fluorescence microscopic analysis, we show that bicyclomycin-dependent cell filamentation is associated with SOS response. RecA-GFP filaments were found to colocalize with the damaged DNA sites in the cell. Further analysis revealed that the genomic DNA was partitioned but the cell septum formation was severely affected under BCM treatment. Furthermore, we observed biofilm formation by E. coli after BCM treatment. We hypothesize that ROS production after BCM treatment could lead to cell filamentation in bacteria. A better understanding of the mode of toxicity of BCM will help us design better antibiotic treatment regimes for clinical practices, including combinatorial drug therapies. The cell filamentation phenotype observed after BCM treatment makes this antibiotic a promising drug for phage-antibiotic synergy (PAS) therapy.

Abiotrophia defectiva Endophthalmitis Post-Keratoplasty – A Case Report and Literature Review

ABSTRACT Purpose To report the first case of acute Abiotrophia defectiva endophthalmitis post-keratoplasty and review the current literature. Methods A 47-year-old male, post-keratoplasty, presented with vision loss and severe anterior chamber reaction. Diagnostic investigations included vitreous cultures and molecular analysis. Results Abiotrophia defectiva was identified. Despite aggressive treatment, visual acuity remained low. We reviewed a total of 14 post-procedural cases of A. defectiva endophthalmitis, focusing on antibiotic and steroidal treatment regimens and long-term prognosis. Conclusion We emphasize aggressive treatment of external disease prior to intraocular surgery. In cases of A. defectiva endophthalmitis, we advocate judicious use of steroids.

Comparison of Empiric Antibiotic Treatment Regimens for Hospitalized, Non-severe Community-acquired Pneumonia: A Retrospective, Multicenter Cohort Study

PurposeConsensus guidelines for hospitalized, non-severe community-acquired pneumonia (CAP) recommend empiric macrolide + β-lactam or respiratory fluoroquinolone monotherapy in patients with no risk factors for resistant organisms. In patients with allergies or contraindications, doxycycline + β-lactam is a recommended alternative. The purpose of this study was to compare differences in outcomes among guideline-recommended regimens in this population. MethodsThis retrospective, multicenter cohort study included patients ≥18 years of age with CAP who received respiratory fluoroquinolone monotherapy, empiric macrolide + β-lactam, or doxycycline + β-lactam. Major exclusion criteria included patients with immunocompromising conditions, requiring vasopressors or invasive mechanical ventilation within 48 hours of admission, and receiving less than 2 days of total antibiotic therapy. The primary outcome was in-hospital mortality. Secondary outcomes included clinical failure, 14- and 30-day hospital readmission, and hospital length of stay. Safety outcomes included incidence of new Clostridioides difficile infection and aortic aneurysm ruptures. FindingsOf 4685 included patients, 1722 patients received empiric respiratory fluoroquinolone monotherapy, 159 received empiric doxycycline + β-lactam, and 2804 received empiric macrolide + β-lactam. Incidence of in-hospital mortality was not observed to be significantly different among empiric regimens (doxycycline + β-lactam group: 1.9% vs macrolide + β-lactam: 1.9% vs respiratory fluoroquinolone monotherapy: 1.5%, P = 0.588). No secondary outcomes were observed to differ significantly among groups. ImplicationsWe observed no differences in clinical or safety outcomes among three guideline-recommended empiric CAP regimens. Empiric doxycycline + β-lactam may be a safe empiric regimen for hospitalized CAP patients with non-severe CAP, although additional research is needed to corroborate these observations with larger samples.

Gut microbiome and antibiotic resistance effects during travelers' diarrhea treatment and prevention.

The travelers' gut microbiome is potentially assaulted by acute and chronic perturbations (e.g., diarrhea, antibiotic use, and different environments). Prior studies of the impact of travel and travelers' diarrhea (TD) on the microbiome have not directly compared antibiotic regimens, and studies of different antibiotic regimens have not considered travelers' microbiomes. This gap is important to be addressed as the use of antibiotics to treat or prevent TD-even in moderate to severe cases or in regions with high infectious disease burden-is controversial based on the concerns for unintended consequences to the gut microbiome and antimicrobial resistance (AMR) emergence. Our study addresses this by evaluating the impact of defined antibiotic regimens (single-dose treatment or daily prophylaxis) on the gut microbiome and resistomes of deployed servicemembers, using samples collected during clinical trials. Our findings indicate that the antibiotic treatment regimens that were studied generally do not lead to adverse effects on the gut microbiome and resistome and identify the relative risks associated with prophylaxis. These results can be used to inform therapeutic guidelines for the prevention and treatment of TD and make progress toward using microbiome information in personalized medical care.

Empiric antibiotic treatment for periprosthetic joint infections: a national survey in The Netherlands.

Early periprosthetic joint infection (PJI) is generally treated by means of debridement, antibiotics and implant retention (DAIR). Subsequently, empiric antibiotic therapy is commenced directly after surgery which is important for the successful treatment of PJI. The aim of this study is to evaluate current nationwide empiric antibiotic treatment regimens for PJI in the Netherlands. An electronic 15-question survey addressing the empiric antibiotic treatment strategy for PJI following THA or TKA was sent to orthopaedic surgeons in all Dutch hospitals in April 2019. Orthopaedic surgeons active in every single Dutch orthopaedic hospital (n=69) were approached. At least one surgeon in every hospital completed the survey (100% response rate). A protocol dictating the empiric antibiotic treatment following DAIR was used in 87% (60 hospitals). Among all hospitals, 72% (50 hospitals) used antibiotic monotherapy and 28% (19 hospitals) used combination therapy. Cefazolin was the most commonly used regimen in centres opting for monotherapy (42%, 29 hospitals). Similar regimens were used for the empiric treatment of suspected early PJI after revision surgery and for acute hematogenous PJI. In septic patients, combination therapy was preferred (64%). 81% (56 hospitals) incubated tissue biopsies for a minimum of 10 days whereas 16% (9 hospitals) indicated an incubation period of 7 days or less. Even in a small country such as the Netherlands there seems to be no uniformity regarding empiric antibiotic treatment for PJI. Increased uniformity regarding empiric treatment could be an important first step in improving PJI treatment.

Repurposing of statins for Buruli Ulcer treatment: antimicrobial activity against Mycobacterium ulcerans.

Mycobacterium ulcerans causes Buruli Ulcer, a neglected infectious skin disease that typically progresses from an early non-ulcerative lesion to an ulcer with undermined edges. If not promptly treated, these lesions can lead to severe disfigurement and disability. The standard antibiotic regimen for Buruli Ulcer treatment has been oral rifampicin combined with intramuscular streptomycin administered daily for 8 weeks. However, there has been a recent shift toward replacing streptomycin with oral clarithromycin. Despite the advantages of this antibiotic regimen, it is limited by low compliance, associated side effects, and refractory efficacy for severe ulcerative lesions. Therefore, new drug candidates with a safer pharmacological spectrum and easier mode of administration are needed. Statins are lipid-lowering drugs broadly used for dyslipidemia treatment but have also been reported to have several pleiotropic effects, including antimicrobial activity against fungi, parasites, and bacteria. In the present study, we tested the susceptibility of M. ulcerans to several statins, namely atorvastatin, simvastatin, lovastatin and fluvastatin. Using broth microdilution assays and cultures of M. ulcerans-infected macrophages, we found that atorvastatin, simvastatin and fluvastatin had antimicrobial activity against M. ulcerans. Furthermore, when using the in vitro checkerboard assay, the combinatory additive effect of atorvastatin and fluvastatin with the standard antibiotics used for Buruli Ulcer treatment highlighted the potential of statins as adjuvant drugs. In conclusion, statins hold promise as potential treatment options for Buruli Ulcer. Further studies are necessary to validate their effectiveness and understand the mechanism of action of statins against M. ulcerans.

Bacterial etiology, antibiotic resistance profile and foot ulcer associated amputations in individuals with Type II diabetes mellitus

ObjectiveIn this study, bacterial etiology, antibiotic resistance profile and clinical outcomes of foot ulcer associated amputations in persons with diabetes were analyzed. MethodsA total of 126 persons with Diabetic Foot Ulcer (DFU) admitted in surgical ward from June 2016 to May 2018 were included in this study. Foot ulcers were categorized as per Wagner's classification. Tissue samples obtained from the ulcers were processed for bacterial cultures using conventional techniques. Antibiotic sensitivity of the isolates was done by Kirby-Bauer’s Disc Diffusion method. ResultsOut of 126 persons with diabetes, 74.6% of them had diabetes for 1–5 years. The minimum and maximum levels of HbA1c were 3% and 10.7%, respectively. Majority (58.7%) of the persons with diabetes had foot ulcers for less than a month. Wagner’s grade 3 ulcer was found to be high (38.1%) among the studied patients. Amputation due to foot ulcer was done in 28.6% of patients of which most of them were under insulin therapy. About 75% of amputated patients had DFU which was complicated by Gram-negative bacterial (GNB) infections. Escherichia coli (27.4%) was the predominant bacterium isolated among the GNB where as Staphylococcus aureus (13.4%) was the predominant one among Gram-positive bacteria. S. aureus isolates were highly resistant to penicillin (85%) followed by gentamicin (45.5%) and ciprofloxacin (40.9%). Enterobacteriaceae isolates showed high level of resistance to co-trimoxazole (84.4%). Imipenem was the most sensitive drug (100%) against GNB isolated from DFU. ConclusionIn this study, the Gram-negative bacteria are the major aetiological agents isolated from the amputated patients with diabetes mellitus. Incidence of multi-drug resistant bacteria associated DFU could be the major burden and limit the availability of antibiotic treatment regimens.

1173 What Influences Taylor Spatial Frame Effectiveness in the Treatment of Tibial Osteomyelitis? A Major Trauma Centre Perspective

Abstract Aim Treatment of tibial osteomyelitis can be challenging, with numerous complications possible during rehabilitation. We report on the usage of the Taylor Spatial Frame (TSF) and analyse factors that affect outcomes. Method Between 2015-2020, 51 patients were treated with TSF for osteomyelitis at a Major Trauma Centre. Demographic, infection, and treatment factors were collected, with microbiology results, antibiotic treatment regimes, and time to partial weight-bear (PWB) and full weight-bear (FWB) prescriptions also noted. Outcomes of complications and time to union were obtained. Results Radiological union was achieved at mean 11.0 months. Mean follow up was 24.1 months. Six/three patients were further treated with fusion/amputation respectively. Mean treatment time with TSF was 12.1 months. 78% had some complications, with pin-site infection, malunion, and non-union being most prevalent. Staphylococcus epidermidis in bone debridement microbiology was significantly negatively associated with pin-site infection (OR = 0.093, 95% CI [0.011-0.828] ) and malunion (OR = 0.698 95% CI[0.573-0.849]), and enterococcus with non-union (OR = 0.775, 95% CI [0.656-0.916] ), during the treatment period. Time to union was significantly positively associated with time from admission to debridement (p = 0.035), time TSF was in (p = 0.021), presence of any complications (p = 0.045), bone loss complication (p = 0.037), time to FWB prescription (p = 0.001). Conclusions We have analysed the effectiveness of TSF in the treatment of tibial osteomyelitis, and elucidated the most important injury, treatment and rehabilitation factors that affect outcome. The negative bacterial-complication cross associations could be due to successful eradication as culture specific antibiotics were used postoperatively. Earlier patient full weight bearing could enhance callous formation leading to faster union.