Use Of Quinolones Research Articles

Revolutionizing Quinolone Development for DNA Gyrase Targeting; Discovering the Promising Approach to Fighting Microbial Infections

Abstract: DNA gyrase is a type II topoisomerase enzyme that can cause negative supercoiling in DNA by using the energy produced by ATP hydrolysis. There are two main types of topoi-somerases: type I and type II. Type I enzymes cut a single strand of DNA and are further clas-sified as type IA if they connect to a 5′ phosphate of DNA, or type IB if they link to a 3′ phos-phate. Type II topoisomerases break both strands, creating a staggered double-strand break. Antimicrobial resistance is a major concern for the global healthcare system. Resistance is the ability of microorganisms to neutralize and withstand antimicrobial drugs previously used to treat microbial infections. Some known classes of DNA gyrase inhibitors are coumarins, cyclo-thialidines, and quinolones. Antimicrobial medicines such as quinolones have been widely used to treat microbiological diseases. However, the increased use of quinolones has led to the emer-gence of quinolone-resistant bacteria, which poses a serious risk to public health. Microorgan-isms can cause resistance due to changes in the target enzymes, DNA gyrase, and topoisomerase IV, which are responsible for transcription and DNA replication. Additionally, differences in drug entry and efflux may also play a role in resistance. Plasmids that produce the Qnr protein can mediate resistance to quinolones by protecting the quinolone targets from inhibition. This review aims to revolutionize the discovery of quinolone-based antibiotics, specifically targeting DNA gyrase, a critical enzyme in bacterial DNA replication, to enhance the efficacy and spec-ificity of anti-microbail agents against microbial infections.

Returned Rate and Changed Patterns of Systemic Antibiotic Use in Ambulatory Care in Hungary after the Pandemic-A Longitudinal Ecological Study.

The COVID-19 pandemic affected the epidemiology of infectious diseases and changed the operation of health care systems and health care seeking behavior. Our study aimed to analyze the utilization of systemic antibiotics in ambulatory care in Hungary after the COVID-19 pandemic and compare it to the period before COVID. We defined three periods (24 months each): Before COVID, COVID, and After COVID. Monthly trends in systemic antibiotic (J01) use were calculated using the WHO ATC-DDD index and expressed as DDD/1000 inhabitants/day (DID) and number of exposed patients per active agent. The data were further categorized by the WHO AWaRe classification. In the After COVID period, we detected almost the same (11.61 vs. 11.11 DID) mean monthly use of systemic antibiotics in ambulatory care compared to the Before COVID period. We observed a decrease in the seasonality index in the After COVID period (46.86% vs. 39.86%). In the After COVID period, the use of cephalosporins and quinolones decreased significantly, while in the case of macrolides, a significant increase was observed compared to the Before COVID period, with excessive azithromycin use (66,869 vs. 97,367 exposed patients). This study demonstrated significant changes in the pattern of ambulatory care antibiotic use in Hungary.

Mucositis-associated bloodstream infections in adult haematology patients with fever during neutropenia: risk factors and the impact of mucositis severity

PurposeHaematology patients with high-risk neutropenia are prone to mucosal-barrier injury-associated laboratory-confirmed bloodstream infections (MBI-LCBI). We assessed risk factors for MBI-LCBI including candidaemia in neutropenic haematology patients with fever.MethodsThis prospective observational study was performed in six dedicated haematology units in the Netherlands. Eligible haematology patients had neutropenia < 500/mL for ≥ 7 days and had fever. MBI-LCBIs were classified according to Centers for Disease Control (CDC) definitions and were followed until the end of neutropenia > 500/mL or discharge.ResultsWe included 416 patients from December 2014 until August 2019. We observed 63 MBI-LCBIs. Neither clinical mucositis scores nor the blood level of citrulline at fever onset was associated with MBI-LCBI. In the multivariable analysis, MASCC-score (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05 to 1.29 per point decrease), intensive chemotherapy (OR 3·81, 95% CI 2.10 to 6.90) and Pichia kudriavzevii (formerly Candida krusei) colonisation (OR 5.40, 95% CI 1.75 to 16.7) were retained as risk factors for MBI-LCBI, while quinolone use seemed protective (OR 0.42, 95% CI 0.20 to 0.92). Citrulline level (OR 1.57, 95% CI 1.07 to 2.31 per µmol/L decrease), active chronic obstructive pulmonary disease (OR 15.4, 95% CI 1.61 to 14.7) and colonisation with fluconazole-resistant Candida (OR 8.54, 95% CI 1.51 to 48.4) were associated with candidaemia.ConclusionIn haematology patients with fever during neutropenia, hypocitrullinaemia at fever onset was associated with candidaemia, but not with bacterial MBI-LCBI. Patients with intensive chemotherapy with a low MASCC-score and colonisation with Pichia kudriavzevii had the highest risk of MBI-LCBI.Trial registrationClinicalTrials.gov (NCT02149329) at 19-NOV-2014.

Antibiotic Prescribing Practices on Hospital Discharge for Management of Urinary Tract Infections: A Single Center Study

Background: Appropriate antibiotic use has been described as one of the key strategies in tackling antibiotic resistance. Although the majority of antimicrobial therapy is completed following discharge, there lacks clear guidance in addressing antibiotic stewardship in the outpatient setting. Particularly, broader coverage as well as longer durations of therapy are often encountered following hospitalization. In our study we examine the various antibiotic prescribing practices on hospital discharge for management of urinary tract infections (UTI). Methods: We conducted a single-center, retrospective observational chart review of patients discharged from St. Francis Hospital and Medical Center in Hartford between May and July 2022. Medical records were reviewed for patients who were prescribed antibiotic therapy for management of UTI and met inclusion criteria. Variables of interest included type of UTI treated, antibiotic used, duration of antibiotics during and following hospitalization, fluoroquinolone use, as well reported adverse events. Total duration of therapy was defined as days on susceptible antimicrobials with appropriate source control. Results: A total of 84 patients met inclusion criteria. 44 received treatment for simple UTI (sUTI) and 40 for complicated UTI (cUTI). Figure 1 shows the various organisms identified on culture. The most common antimicrobials prescribed on discharge were cefpodoxime and ciprofloxacin [figure 2]. Quinolones were prescribed in 11.4% of sUTIs and 39.1% of cUTIs on hospital discharge. Of those, only one patient had no alternative to quinolone use due to drug allergies. The mean duration of therapy for treatment of sUTI was 6.4 days total (SD 2.40) with 3.9 days outpatient (SD 1.78). The mean duration of therapy for treatment of cUTI was 10.9 days total (SD 3.62) with 6.7 days outpatient (SD 2.99). Comparison of mean durations is shown in figure 3. In 49% of all cases (including both sUTI and cUTI) patients received greater than 7 days of antimicrobial therapy. Conclusion: There is increased evidence favoring shorter courses of antimicrobial therapy for management of both simple and complicated UTIs. A 7-day course has been shown as effective duration of therapy for cUTI with appropriate source control, regardless of presence of bacteremia. Results from our single center-study show both sUTI and cUTI are subject to unnecessarily prolonged durations of therapy on hospital discharge. In addition we noted a significant use of fluoroquinolones in cUTI treatment. We believe stewardship interventions at time of discharge may particularly benefit shorter courses of therapy for cUTI as well as reduced quinolone use.

Antibiotic use during radical surgery in stage I-III colorectal cancer: correlation with outcomes?

AimsAccumulating evidence indicates that the use of antibiotics (ATBs) in cancer patients is potentially correlated with patient prognosis. Interestingly, the use of these agents is not uncommon in colorectal cancer (CRC) patients during surgery; however, their prognostic value in the clinic has never been addressed.Materials and methodsData on ATB use during surgery, including the cumulative defined daily dose (cDDD) and the number of categories, were collected. Differences in the clinical data between the low and high cDDD subgroups and between subgroups with ≤ 4 and >4 categories. Additionally, the disease-free survival (DFS) and overall survival (OS) among these subgroups and the specific categories were compared. Finally, a Cox proportional hazard model was used to validate the risk factors for the outcome.ResultsThe number of categories, rather than the cDDD, was a significant predictor of both DFS (P = 0.043) and OS (P = 0.039). Patients with obstruction are more likely to have a high cDDD, whereas older patients are more likely to have multiple categories. There were no significant differences in the DFS (log rank = 1.36, P = 0.244) or OS (log rank = 0.40, P = 0.528) between patients in the low- and high-cDDD subgroups, whereas patients with ≤ 4 categories had superior DFS (log rank = 9.92, P = 0.002) and OS (log rank = 8.30, P = 0.004) compared with those with >4 categories. Specifically, the use of quinolones was harmful to survival (DFS: log rank = 3.67, P = 0.055; OS: log rank = 5.10, P = 0.024), whereas the use of macrolides was beneficial to survival (DFS: log rank = 12.26, P < 0.001; OS: log rank = 9.77, P = 0.002). Finally, the number of categories was identified as an independent risk factor for both DFS (HR = 2.05, 95% CI: 1.35–3.11, P = 0.001) and OS (HR = 1.82, 95% CI: 1.14–2.90, P = 0.012).ConclusionsThe cDDD of ATBs during surgery in stage I-III CRC patients did not correlate with outcome; however, patients in multiple categories or a specific category are likely to have inferior survival. These results suggest that particular caution should be taken when selecting ATBs for these patients in the clinic.

Systematic review on the safety of the use of quinolones in the pediatric population

Background: The safety of fluoroquinolones in the pediatric population has been a matter of concern due to the potential for adverse effects such as growth cartilage toxicity. Despite their broad antimicrobial spectrum and efficacy, the prescription of fluoroquinolones in children and adolescents is limited by the risk of arthralgias and other side effects. This study aims to evaluate the safety of fluoroquinolones in pediatric patients and the impact of regulatory actions on their prescription. Material and methods: A systematic review of studies investigating the safety of fluoroquinolones in the pediatric population was conducted. Studies that met specific inclusion criteria were selected, and relevant information on the decrease in fluoroquinolone prescriptions and their adverse effects was extracted. Results: In the study on the safety and tolerability of quinolones in the pediatric population, 22% (199/904) of patients experienced adverse events following treatment with quinolones. Gastrointestinal disorders, such as nausea and diarrhea, were the most frequent, affecting 12% (108/904) of patients. This was followed by skin rashes and effects on the central nervous system, at 5% (45/904) and 3% (27/904) respectively. Moxifloxacin demonstrated good tolerability across all age cohorts, without significant joint or neuropathic adverse findings. Specific safety studies of moxifloxacin confirmed its safety, showing no significant differences in safety variables compared to other antibiotics. Conclusion: It is crucial to continue monitoring the safety of fluoroquinolones in the pediatric population to ensure an adequate balance between the benefits and risks of their use.

Comparative genomic analysis of Brazilian Mesomycoplasma ovipneumoniae strains revealed genomic differences associated with the geographic origin and health status and mutations in the gyrA

Sheep respiratory disease (SRD) is a multifactorial illness commonly affecting sheep. Mesomycoplasma (Mycoplasma) ovipneumoniae is one of the most important etiological agents of SRD and should be better understood, especially in countries where it was recently detected, such as Brazil. Also, the intensive use of quinolones in mycoplasmal infections increases the selective pressure for resistance to this drug class, and no data about antimicrobial resistance in Brazil is available. Therefore, this study aimed to perform a comparative genomic analysis of newly isolated Brazilian M. ovipneumoniae strains, identify point mutations in target genes that may be associated with antibiotic resistance, and perform a phylogenomic analysis of these strains with available genome representatives of M. ovipneumoniae. Glucose-fermenting fried egg-like colonies identified as M. ovipneumoniae were obtained after a culture of tracheobronchial lavage from infected sheep. The genomes were sequenced, de novo assembled and comparatively evaluated. Important putative virulence factors were detected in all isolates: the analysis of the average nucleotide homology of all these genes with the M. ovipneumoniae ATCC 29419 revealed associations between clpB, lgt, tuf, and dnaJ genes and geographic location. In addition, nucleotide substitutions in a few positions of the Quinolone-Resistant Determinant Region of the gyrA gene, including the Ser83Ala, were detected. The phylogenomic analysis showed that the Brazilian isolates belonged to two different clades corresponding to geographic location, and the isolates from São Paulo showed high similarity, which differs from isolates from Rio de Janeiro. This first genomic analysis of the Brazilian M. ovipneumoniae genomes demonstrates strain segregation according to location and health status, reinforcing the importance of continuous surveillance and diagnostics of this bacteria causing sheep respiratory disease in the Brazilian flocks.

Risk factors for bacteremia and mortality due to multidrug-resistant Acinetobacter baumannii: a retrospective study.

This research aimed to determine the relationships between the risk factors for nosocomial multidrug-resistant Acinetobacter baumannii (MDRAB) bacteremia and associated mortality. We analyzed 144 patients treated for A. baumannii bacteremia, including 120 patients with MDRAB bacteremia, from March 2015 to March 2020, in this retrospective study. The overall bacteremia-related mortality rate was 48.6%. The mortality rates were 25.0% and 53.3% for non-MDRAB and MDRAB bacteremia, respectively. Risk factors for the development of MDRAB bacteremia were prior use of cephalosporins [odds ratio (OR): 8.62; P<.001], carbapenems (OR: 15.04; P<.001), or quinolones (OR: 5.02; P=.040); indwelling urinary catheters (OR: 21.38; P<.001); and respiratory tract as the source of bacteremia (OR: 75.33; P<.001). Patients with elective surgeries were inclined to develop non-MDRAB bacteremia (OR: 0.45; P=.029). High scores in the Acute Physiology and Chronic Health Evaluation II (OR: 1.321; P<.001) and Sequential Organ Failure Assessment (OR: 1.326; P<.001) were risk factors for mortality from MDRAB infection. In summary, higher mortality rates occur in patients with MDRAB bacteremia, and risk factors include prior use of cephalosporins, carbapenems, or quinolones. Urinary catheters and the respiratory tract as sources of the infection increase the risk of MDRAB bacteremia.

Quinolone Use during the First Trimester of Pregnancy and the Risk of Atopic Dermatitis, Asthma, and Allergies of Offspring during 2011 to 2020.

Many pregnant women receive antibiotic treatment for infections. We investigated the association between quinolone use in the first trimester of pregnancy and the risk of adverse health outcomes for the child in Korea. This nationwide, population-based cohort study used data on mother-child pairs from the National Health Insurance claims database. This study cohort included 2,177,765 pregnancies from January 1, 2011, to December 31, 2020, and 87,456 women were prescribed quinolones during pregnancy. After propensity score matching, the final number of study subjects was 84,365 for both quinolone and non-antibiotic users. We examined the subjects' exposure to quinolone antibiotics. The main outcome measures were absolute and relative risks of atopic dermatitis, asthma, and allergies. We adjusted for potential confounders. Quinolones were prescribed at least once during the first trimester in 4.01% of pregnancies. Quinolone users had significantly higher absolute risks than non-antibiotic users for atopic dermatitis, asthma, and allergies, with significantly elevated risk ratios (RRs) for these conditions (atopic dermatitis: RR, 1.09; 95% confidence interval [CI], 1.08-1.11, asthma: RR, 1.04; 95% CI, 1.03-1.05, and allergies: RR, 1.10; 95% CI, 1.08-1.13). We found that quinolone exposure during the first trimester of pregnancy increased the risk of atopic dermatitis, asthma, and allergies. This study could provide physicians with useful information when selecting antibiotics for pregnant women.

Effective extraction and determination of 24 quinolones in water and egg samples using a novel magnetic covalent organic framework combined with UPLC-MS/MS.

The excessive use of quinolones (QNs) has seriously threatened human health. In this study, a novel functionalized magnetic covalent organic framework Fe3O4@SiO2@Ah-COF was fabricated with biphenyl-3,3',5,5'-tetracarbaldehyde and hydrazine hydrate (85%) as monomers and was used as a magnetic solid-phase extraction (MSPE) absorbent for the determination of 24 QNs in water and egg samples through ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The extraction parameters of MSPE were optimized, including pH, adsorbent dosage, adsorption time, and eluent type. An effective and rapid detection method was then established, which showed good linearity (R2 ≥ 0.9990), low limits of detection (0.003-0.036 μg L-1) and low limits of quantitation (0.008-0.110 μg L-1) for QNs. The good recoveries of 24 QNs in water and egg samples were in the range of 70.3-106.1% and 70.4-119.7%, respectively, with relative standard deviations lower than 10% (n = 5). As a result, Fe3O4@SiO2@Ah-COF is a promising magnetic adsorbent, and the established method was successfully applied for the determination of 24 QNs in water and egg samples.

Regional and National Trends in Consumption of Antimicrobials in Pakistan; Pre and Post-COVID (2019-2021).

Efforts to combat antimicrobial resistance, a growing public health problem in Pakistan, have been hampered by the lack of high-quality national and provincial-level antimicrobial consumption data. The singular objective of this retrospective study was to measure antimicrobial consumption over 3 years between 2019 and 2021. The study was designed to estimate antimicrobial consumption at National and Regional levels. Antimicrobial consumption data was collected by IQVIA covering 110 districts of Pakistan in which 88% of sales are census (accurate sales collected directly from distributors), whereas 12% of sales (sales of 300 pharmacies) are projected on the national level. To determine the usage for 3 consecutive years, the consumption of antibiotics was calculated as defined daily doses (DDD) of antibiotics per 1000 inhabitants per day (DID). The results of our study demonstrated a steep increase in the consumption of antimicrobials from 2019 to 2021. An increase in consumption of most classes of antibiotics was observed both nationally and Regionally. Quinolones, penicillins (co-amoxiclav), macrolides, and third-generation cephalosporins remained the most frequently used antibiotics nationally. A 40% increase in intravenous use of antimicrobials was observed between 2019 and 2021 at the national level. Moxifloxacin, Levofloxacin, Ciprofloxacin, and linezolid were the most commonly used intravenous antibiotics. Region 7 (Peshawar) demonstrated the highest consumption, followed by Region 1 (Karachi) and Region 6 (Faisalabad). Among the most commonly used antibiotics, the use of third-generation cephalosporin (cefixime), quinolones, penicillins (amoxicillin + clavulanic acid), and macrolides (azithromycin) was most noticeable in all regions, particularly in those with the higher consumption of antibiotics. Although the increase in consumption of all antibiotics is concerning, the steep increase in the use of watch and reserve category antibiotics during the study period calls for immediate actions to limit and regulate their usage.

2195. Impact of Optimizing Urine Culture Susceptibility Reports on Prescribing of Antimicrobials in Outpatients at the Atlanta VA Health Care System (AVAHCS)

Abstract Background To encourage appropriate prescribing in uncomplicated urinary tract infections (UTIs), the AVAHCS optimized urine susceptibility reports by adding comments guiding selection of narrow-spectrum beta-lactams for Enterococcus spp and certain Enterobacterales (E. coli, K. pneumoniae, Proteus spp) and hiding the susceptibility of levofloxacin for Enterococcus spp. The purpose of this study is to determine the impact of these changes on antibiotic selection in outpatients. Methods This study was a retrospective chart review of patients with positive urine cultures for the target organisms from March - December 2019 and March - December 2022. Patients were included if they had urine cultures that resulted with one of the target organisms and received UTI treatment. Those excluded had positive blood cultures or were hospitalized at the time of sample collection, had a previous urine culture or received treatment for UTI within 30 days, had a urological procedure in the preceding 12 months, or had a polymicrobial culture result. The primary outcome was the percent change in the use of quinolones before and after implementation. Secondary outcomes included the percent change in the use of aminopenicillins and cephalosporins for Enterococcus spp and Enterobacterales, respectively. Results For Enterococcus spp, there was a 29.2% decrease in the selection of quinolones as definitive therapy. There was a 37.1% increase in the use of aminopenicillins as definitive therapy. For Enterobacterales, there was a 15% decrease in the selection of quinolones as definitive therapy. There was a 13.3% increase in the use of first-generation cephalosporins as definitive therapy. Conclusion For Enterococcus spp UTI, following suppression of levofloxacin from the C&amp;S reports and addition of provider comments, quinolones were less likely to be prescribed and aminopenicillins were more likely to be prescribed. In Enterobacterales UTI, following addition of prescriber comments, quinolones were less likely to be prescribed and first-generation cephalosporins were more likely to be prescribed, though the increase was less pronounced than was seen in the Enterococcus spp group. These results suggest the combination of susceptibility suppression and comments was more impactful than a comment alone. Disclosures All Authors: No reported disclosures

2949. Emergency Department (ED) Discharge Antibiotic Prescription Review by Hospital Pharmacists at a Large Academic Medical Center

Abstract Background Direct patient discharge from the Emergency Department (ED) presents an ideal time to promote antimicrobial stewardship (AS). On March 1, 2021 we initiated a pilot program where ED pharmacists conduct a review of discharge antibiotic prescriptions (abx Rxs). The aim of this program is to ensure appropriate discharge abxs. Willow Pharmacy Epic Analysts, ED and AS pharmacists collaborated on this program which included Epic integration of Rx Discharge Track Board, ED Discharge InBasket, ED Discharge Rx iVent and AS-led education sessions. Methods Data for 2022 ED patients with discharge abx Rxs and iVents were extracted via Epic Reports. The first encounter per patient was included. We compared discharge abx Rxs and patient outcome data in Pharmacy vs No Pharmacy Review Groups (PRG, NPRG). Pharmacy iVents were used as a process measure. Results Among 5747 ED adult patients with discharge abx Rxs, 2638 (46%) were reviewed by pharmacy (PRG). PRG and NPRG had similar prevalence of chronic pulmonary disease (12% vs. 13%), diabetes mellitus (9% vs. 10%), malignancy (8% vs. 9%), peripheral vascular disease (6% vs. 8%), renal disease (4% vs. 5%), and HIV (1% vs. 2%) despite a difference in mean Charlson Comorbidity Index (0.64 vs 0.75, p&amp;lt; 0.01). The primary ED diagnosis was skin and soft tissue, urinary, intra-abdominal infections and pneumonia (25 vs 23%, 18 vs 17%, 8 vs 9%, 5 vs 6%, respectively all p=NS). In PRG, discharge abxs demonstrated an increase use of penicillin (26 vs 24%, p=0.017) and 2nd generation cephalosporin (17 vs 14%, p&amp;lt; 0.001). The PRG also decreased use of 3rd generation cephalosporin (11 vs 12%, p=NS), quinolones (6 vs 7%, p=NS) and clindamycin (1.7 vs 2.4%, p=NS). There was no difference in ED length of stay (LOS 4.8h in each group), C. difficile infection (CDI) within 8 weeks (0.1 vs 0.2%, p=NS), and 30 days repeat ED visit or inpatient admission with the same diagnosis as index ED encounter (2.8 vs 2.6%, p=NS). Pharmacists intervened in 10% (272/2638) of ED abx Rxs with 92% (249/272) acceptance rate. The top 3 pharmacy interventions were recommending alternative abx (42%), dose optimization (31%) and abx duration (6%). Conclusion Engaging pharmacists in ED discharge Rxs review resulted in use of narrower spectrum abx with lower CDI risk without any negative impact on ED LOS and clinical outcomes. Disclosures All Authors: No reported disclosures

Urinary Tract Infections in Men in Primary Care in Catalonia, Spain.

Antimicrobial resistance is a major global problem that is primarily driven by the excessive and inappropriate utilization of antibiotics. Urinary tract infections (UTIs) are frequent in primary health care (PHC) and are typically treated with antibiotics. There is ample evidence on the management of this condition in women but not in men. The aim of this study was to describe the epidemiology of UTIs in men in Catalonia, Spain. We conducted a population-based observational cohort study that included male patients diagnosed with UTI within our SIDIAP and CMBD database during the period from 2012 to 2021. UTI diagnoses were grouped into five main groups (cystitis, prostatitis, orchitis and epididymitis, urethritis, and pyelonephritis). Of the 316,762 men with at least one recorded UTI episode, the majority were registered with a diagnosis of cystitis in PHC (212,958 patients). Quinolones were the most commonly recorded treatment for UTIs (between 18.3% and 38.6%, depending on the group), except for urethritis in which a combination of antibiotics (36.7%) was most frequently used. The treatment duration period was between 9 days and 18 days, except for the prostatitis group, in which treatment was extended to 21 days. Urine cultures were documented in up to 30% in the cystitis group. Pyelonephritis was the category linked to most septicemia cases (3.0%). Conclusions: This is the first study to assess UTIs in men using a large PHC database in Spain. The sociodemographic characteristics of our sample are similar to other studies in the literature. In our setting, the use of quinolones for the treatment of UTIs is the most registered, and its duration was between 9 days and 18 days, despite the fact that resistance to quinolones exceeds 20% of the strains in our area.

Tularemia – a re-emerging disease with growing concern

Tularemia caused by Gram-negative, coccobacillus bacterium, Francisella tularensis, is a highly infectious zoonotic disease. Human cases have been reported mainly from the United States, Nordic countries like Sweden and Finland, and some European and Asian countries. Naturally, the disease occurs in several vertebrates, particularly lagomorphs. Type A (subspecies tularensis) is more virulent and causes disease mainly in North America; type B (subspecies holarctica) is widespread, while subspecies mediasiatica is present in central Asia. F. tularensis is a possible bioweapon due to its lethality, low infectious dosage, and aerosol transmission. Small mammals like rabbits, hares, and muskrats are primary sources of human infections, but true reservoir of F. tularensis is unknown. Vector-borne tularemia primarily involves ticks and mosquitoes. The bacterial subspecies involved and mode of transmission determine the clinical picture. Early signs are flu-like illnesses that may evolve into different clinical forms of tularemia that may or may not include lymphadenopathy. Ulcero-glandular and glandular forms are acquired by arthropod bite or handling of infected animals, oculo-glandular form as a result of conjunctival infection, and oro-pharyngeal form by intake of contaminated food or water. Pulmonary form appears after inhalation of bacteria. Typhoidal form may occur after infection via different routes. Human-to-human transmission has not been known. Diagnosis can be achieved by serology, bacterial culture, and molecular methods. Treatment for tularemia typically entails use of quinolones, tetracyclines, or aminoglycosides. Preventive measures are necessary to avoid infection although difficult to implement. Research is underway for the development of effective live attenuated and subunit vaccines.

The Burden of Self-Reported Antibiotic Allergies in Health Care and How to Address It: A Systematic Review of the Evidence.

Antibiotics are the first-line treatment for bacterial infections; however, overuse and inappropriate prescribing have made antibiotics less effective with increased antimicrobial resistance. Unconfirmed reported antibiotic allergy labels create a significant barrier to optimal antimicrobial stewardship in health care, with clinical and economic implications. A systematic review was conducted to summarize the impact of patient-reported antibiotic allergy on clinical outcomes and various strategies that have been employed to effectively assess and remove these allergy labels, improving patient care. The review was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A critical appraisal was conducted on all studies and a narrative synthesis was performed to identify themes. Four themes emerged: the prevalence of antibiotic allergy, impact of antibiotic allergy on antimicrobial prescribing, impact of antibiotic allergy on clinical outcomes, and delabeling strategies to improve clinical outcomes. Of the 32 studies, including 1,089,675 participants, the prevalence of reported antibiotic allergy was between 5% and 35%. Patients with a reported antibiotic allergy had poorer concordance with prescribing guidelines in 30% to 60% of cases, with a higher use of alternatives such as quinolone, tetracycline, macrolide, lincosamide, and carbapenem and lower use of beta-lactam antibiotics. Antibiotic allergy delabeling was identified as an intervention and recommendation to advance the state of the science. There is substantial evidence within the literature that antibiotic allergy labels significantly impact patient clinical outcomes and a consensus that systematic assessment of reported antibiotic allergies, commonly referred to as delabeling, improves the clinical management of patients.

Early treatment response to piperacillin/tazobactam in patients with bloodstream infections caused by non-ESBL ampicillin/sulbactam-resistant Escherichia coli: a binational cohort study

PurposeThis study aimed to compare treatment outcomes for bloodstream infections (BSI) caused by a piperacillin/tazobactam (PIP/TAZ)-susceptible E. coli among three patient groups: BSI caused by ampicillin/sulbactam (AMP/SLB)-resistant isolates treated with PIP/TAZ, BSI caused by AMP/SLB-sensitive isolates treated with PIP/TAZ, and BSI caused by AMP/SLB-resistant isolates treated with another monotherapy.MethodsThis retrospective study was conducted in two academic centres in Europe. Adult patients with E. coli BSI were screened from 2014 to 2020. Inclusion criteria were non-ESBL BSI and initial monotherapy for ≥ 72 h. To reduce the expected bias between the patient groups, propensity score matching was performed. The primary outcome was early treatment response after 72 h and required absence of SOFA score increase in ICU/IMC patients, as well as resolution of fever, leukocytosis, and bacteraemia.ResultsOf the 1707 patients screened, 315 (18.5%) were included in the final analysis. Urinary tract infection was the most common source of BSI (54.9%). Monotherapies other than PIP/TAZ were cephalosporins (48.6%), carbapenems (34.3%), and quinolones (17.1%). Enhanced early treatment response rate was detected (p = 0.04) in patients with BSI caused by AMP/SLB-resistant isolates treated with another monotherapy (74.3%) compared to those treated with PIP/TAZ (57.1%), and was mainly driven by the use of cephalosporins and quinolones (p ≤ 0.03). Clinical success, 28-day mortality, and rate of relapsing BSI did not significantly differ between the groups.ConclusionsOur study suggests that initial use of PIP/TAZ may be associated with reduced early treatment response in E. coli BSI caused by AMP/SLB-resistant isolates compared to alternative monotherapies.

Correlation between antibiotic use and resistance of gram-negative bacteria at a university hospital in Japan from 2013 to 2021: a study using the Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system

ObjectivesThe Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system aggregates information related to antimicrobial resistance (AMR) measures. We aimed to investigate the correlation between antibiotic use and AMR...

Tympanoplasty Healing Outcomes With Use of Postoperative Otic Quinolones.

Tympanoplasty usually results in tympanic membrane perforation (TMP) closure, but healing may be suboptimal (e.g., excess scarring). Factors that have been linked to impaired TM healing have become widely adopted (especially, postoperative use of quinolone ear drops). The aim of this study is to assess the frequency of suboptimal tympanoplasty healing with the use of otic quinolones postoperatively. Retrospective chart review. Tertiary care facility. One hundred patients undergoing tympanoplasty for TMP. Tympanoplasty +/- canalplasty. Healing complications (e.g., granulation tissue, TMP, myringitis, bone exposure, lateralization, anterior blunting, medial canal fibrosis, and canal stenosis) and hearing loss. Charts were reviewed for postoperative healing issues and hearing outcomes at 1 to 2 years postoperatively. TMP closure was found in 93.2%, but 34.2% had healing issues at 1 to 2 years postoperatively, with 20.6% having adverse healing outcomes (perforation (6.9%), granulation tissue (6.9%), medial fibrosis (4.1%), and myringitis, bone exposure, and webbing (all 1.4%). Another 13.7% had notable postoperative issues, such as protracted otorrhea (11.0%), otitis externa (9.6%), otitis media (1.4%), and atelectasis (2.7%). No medical, surgical, or patient factors impacted outcomes. Average air-bone gap at 1 to 2 years did not differ between patients with and without healing issues and patients with other postoperative issues ( p = 0.5). Suboptimal healing is common after tympanoplasty. There may be significant opportunity to improve post-tympanoplasty healing beyond improving the TMP closure rate.

An increasing threat in intensive care units: evaluation of multi-drug-resistant Myroides spp. infections and risk factors

Myroides spp. are Gram-negative bacilli that are commonly found in soil and water, acting as low-level opportunistic pathogens and causing a variety of infections. To assess the risk factors for multi-drug-resistant myroides infections, association with comorbid illnesses, patient care and susceptibility to antibiotics. This retrospective analytical study was conducted in Istanbul Başakşehir Çam and Sakura City Hospital, and included patients with Myroides spp. isolated in their culture samples. Total hospitalization days, first isolation day and 30-day mortality values of the patients were analysed statistically, and P<0.05 was considered to indicate significance. Myroides spp. were isolated from 437 culture samples from 228 patients. Of these cases, 210 (92.1%) were classified as having asymptomatic bacteriuria, and 18 (7.9%) as having an infection caused by Myroides spp. One hundred and seventy-four (76.3%) patients were followed up in the intensive care unit, and total hospitalization days (median 24.5 days) and first isolation day (median 9.5 days) of infected patients were shorter than those for colonized patients (P=0.023 and 0.030, respectively). No difference was found in 30-day mortality between infected and colonized patients (P=0.312). Myroides infections were seen more frequently in patients who were hospitalized for a long time, used broad-spectrum antimicrobials, underwent invasive procedures, and had co-factors such as diabetes and cerebrovascular disease. In addition, the resistance rates of Myroides odoratus were higher than those of Myroides odoratimimus, and the use of quinolones for the treatment of patients with M.odoratimimus infection led to a higher cure rate.