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The discovery of novel structural classes of antibiotics is urgently needed to address the ongoing antibiotic resistance crisis 1-9 . Deep learning approaches have aided in exploring chemical spaces 1,10-15 ; these typically use black box models and do not provide chemical insights. Here we reasoned that the chemical substructures associated with antibiotic activity learned by neural network models can be identified and used to predict structural classes of antibiotics. We tested this hypothesis by developing an explainable, substructure-based approach for the efficient, deep learning-guided exploration of chemical spaces. We determined the antibiotic activities and human cell cytotoxicity profiles of 39,312 compounds and applied ensembles of graph neural networks to predict antibiotic activity and cytotoxicity for 12,076,365 compounds. Using explainable graph algorithms, we identified substructure-based rationales for compounds with high predicted antibiotic activity and low predicted cytotoxicity. We empirically tested 283 compounds and found that compounds exhibiting antibiotic activity against Staphylococcus aureus were enriched in putative structural classes arising from rationales. Of these structural classes of compounds, one is selective against methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci, evades substantial resistance, and reduces bacterial titres in mouse models of MRSA skin and systemic thigh infection. Our approach enables the deep learning-guided discovery of structural classes of antibiotics and demonstrates that machine learning models in drug discovery can be explainable, providing insights into the chemical substructures that underlie selective antibiotic activity., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a major global pathogen with limited treatment options 1 . No new antibiotic chemical class with activity against A. baumannii has reached patients in over 50 years 1 . Here we report the identification and optimization of tethered macrocyclic peptide (MCP) antibiotics with potent antibacterial activity against CRAB. The mechanism of action of this molecule class involves blocking the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane, through inhibition of the LptB 2 FGC complex. A clinical candidate derived from the MCP class, zosurabalpin (RG6006), effectively treats highly drug-resistant contemporary isolates of CRAB both in vitro and in mouse models of infection, overcoming existing antibiotic resistance mechanisms. This chemical class represents a promising treatment paradigm for patients with invasive infections due to CRAB, for whom current treatment options are inadequate, and additionally identifies LptB 2 FGC as a tractable target for antimicrobial drug development., (© 2024. The Author(s).)

BACKGROUND The human microbiota modulates the immune system and forms the surface flora. Antibiotic administration causes dysbiosis in the intestinal flora. It is not clear if antibiotic administration in the community effects the upper airway flora in the mid-term or long-term. This study aims to define long-term influence of antibiotics on upper airway flora. MATERIAL AND METHODS In this prospective study, aerobic microbiological analysis of nasal and nasopharyngeal surfaces was performed. Antibiotic administration history of the last 6 months was retrieved using the social insurance database. Culture results of antibiotic-treated and antibiotic-naïve subjects were compared by Pearson's chi-square test or Fisher's exact test. RESULTS A total of 210 subjects were included in the study. Normal flora were documented in 86 nasal swabs and 99 nasopharyngeal swabs. Most of the remaining cases demonstrated gram-positive bacterial overgrowth. There were 113 subjects who did not receive any antibiotic, and 93% of the remaining 97 patients received broad-spectrum antibiotics. Statistical analysis showed that nasal and nasopharyngeal flora did not change upon antibiotic administration, but antibiotic administration during the last month caused increased methicillin resistance development of coagulase-negative Staphylococcus and Staphylococcus aureus microorganisms. CONCLUSIONS Antibiotic exposure did not lead to perturbations in general composition of upper airway flora within 6 months, although the incidence of methicillin resistance in coagulase-positive and -negative Staphylococci demonstrated significant increases when patients received antibiotic during the last month. This should be considered in case of broad-spectrum antibiotic administration, since methicillin resistance increases the morbidity and mortality of nosocomial Staphylococcus infections.

Antibiotics are used to fight pathogens but also target commensal bacteria, disturbing the composition of gut microbiota and causing dysbiosis and disease 1 . Despite this well-known collateral damage, the activity spectrum of different antibiotic classes on gut bacteria remains poorly characterized. Here we characterize further 144 antibiotics from a previous screen of more than 1,000 drugs on 38 representative human gut microbiome species 2 . Antibiotic classes exhibited distinct inhibition spectra, including generation dependence for quinolones and phylogeny independence for β-lactams. Macrolides and tetracyclines, both prototypic bacteriostatic protein synthesis inhibitors, inhibited nearly all commensals tested but also killed several species. Killed bacteria were more readily eliminated from in vitro communities than those inhibited. This species-specific killing activity challenges the long-standing distinction between bactericidal and bacteriostatic antibiotic classes and provides a possible explanation for the strong effect of macrolides on animal 3-5 and human 6,7 gut microbiomes. To mitigate this collateral damage of macrolides and tetracyclines, we screened for drugs that specifically antagonized the antibiotic activity against abundant Bacteroides species but not against relevant pathogens. Such antidotes selectively protected Bacteroides species from erythromycin treatment in human-stool-derived communities and gnotobiotic mice. These findings illluminate the activity spectra of antibiotics in commensal bacteria and suggest strategies to circumvent their adverse effects on the gut microbiota., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The dearth of new medicines effective against antibiotic-resistant bacteria presents a growing global public health concern 1 . For more than five decades, the search for new antibiotics has relied heavily on the chemical modification of natural products (semisynthesis), a method ill-equipped to combat rapidly evolving resistance threats. Semisynthetic modifications are typically of limited scope within polyfunctional antibiotics, usually increase molecular weight, and seldom permit modifications of the underlying scaffold. When properly designed, fully synthetic routes can easily address these shortcomings 2 . Here we report the structure-guided design and component-based synthesis of a rigid oxepanoproline scaffold which, when linked to the aminooctose residue of clindamycin, produces an antibiotic of exceptional potency and spectrum of activity, which we name iboxamycin. Iboxamycin is effective against ESKAPE pathogens including strains expressing Erm and Cfr ribosomal RNA methyltransferase enzymes, products of genes that confer resistance to all clinically relevant antibiotics targeting the large ribosomal subunit, namely macrolides, lincosamides, phenicols, oxazolidinones, pleuromutilins and streptogramins. X-ray crystallographic studies of iboxamycin in complex with the native bacterial ribosome, as well as with the Erm-methylated ribosome, uncover the structural basis for this enhanced activity, including a displacement of the [Formula: see text] nucleotide upon antibiotic binding. Iboxamycin is orally bioavailable, safe and effective in treating both Gram-positive and Gram-negative bacterial infections in mice, attesting to the capacity for chemical synthesis to provide new antibiotics in an era of increasing resistance., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: The aim of this research study was to compare the situation concerning the use of microbiology testing, the epidemiology of healthcare-associated infection (HAI) and antimicrobial consumption (AMC) in Polish long-term care facilities (LTCFs) with other European countries, using the most recent findings available in the European databases. Furthermore, this study aimed to highlight several basic factors that contribute to the observable differences in AMC between countries participating in the HALT-3 study, especially the relationship with demographic indicators, as well as the health care resources utilization rates., Patients and Methods: The most recent HAIs in Long-Term care facilities Point Prevalence Survey (HALT PPS) was carried out in EU/EEA countries in 2016-2017, and in Poland it was carried out in April-June 2017 in 24 LTCFs. AMC data was collected with use of methodology of the Anatomical Therapeutic Chemical (ATC) classification system of the WHO., Results: In total total in HALT-3 study on the day of the PPS, 5035 out of the 102,301 eligible residents received at least one antimicrobial agent, with prevalence of 4.9%, and in Poland 3.2%. The most common HAIs in the countries included into the study was urinary tract infection with relative frequency of 32%, in Poland it was skin infection, 30.4%. The respiratory tract infections, excluding pneumonia (PNU) were observed in 29.5% of residents in total, in Poland 17.4%, the prevalence rate of PNU were 1.4% and 5.4%, respectively. The lack of microbiological results of HAIs testing concerned the vast majority of all HAIs, 75.8% in total and 81.5% in Poland. The most frequently used antibacterial for systemic use were beta-lactams and the most frequently prescribed antimicrobial agent was 'amoxicillin and enzyme inhibitor'. AMC was closely correlated with the age of the general population (65 years of age and more) and the availability of doctors in general population., Conclusions: A significant problem observed in LTCFs was the empirical use of antibiotics and the scarcity of microbiological testing. In the studied Polish LTCFs, where the age of residents was low, also the AMC was found to be lower., (© 2021. The Author(s).)

Understating how antibiotic tolerance impacts subsequent resistance development in the clinical setting is important to identifying effective therapeutic interventions and prevention measures. This study describes a patient case of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia which rapidly developed resistance to three primary MRSA therapies and identifies genetic and metabolic changes selected in vivo that are associated with rapid resistance evolution. Index blood cultures displayed susceptibility to all (non-beta-lactam) antibiotics with the exception of trimethoprim/ sulfamethoxazole. One month after initial presentation, during the same encounter, blood cultures were again positive for MRSA, now displaying intermediate resistance to vancomycin and ceftaroline and resistance to daptomycin. Two weeks later, blood cultures were positive for a third time, still intermediate resistant to vancomycin and ceftaroline and resistant to daptomycin. Mutations in mprF and vraT were common to all multidrug resistant isolates whereas mutations in tagH, agrB and saeR and secondary mprF mutation emerged sequentially and transiently resulting in distinct in vitro phenotypes. The baseline mutation rate of the patient isolates was unremarkable ruling out the hypermutator phenotype as a contributor to the rapid emergence of resistance. However, the index isolate demonstrated pronounced tolerance to the antibiotic daptomycin, a phenotype that facilitates the subsequent development of resistance during antibiotic exposure. This study exemplifies the capacity of antibiotic-tolerant pathogens to rapidly develop both stable and transient genetic and phenotypic changes, over the course of a single patient encounter., Competing Interests: The authors have declared that no competing interests exist.

Abstract: If wounds are infected with bacteria resistant to an empirical antibiotic regimen, effective wound treatment will be delayed. This can delay wound healing and lengthen hospital stays, increasing the costs to patients. Long-term antibiotic use can also result in minor and major complications, such as diarrhea, antibiotic resistance, or life-threatening leukopenia. Multidrug-resistant (MDR) bacteria make wound treatment even more difficult. Traditionally, surgeons thought that adequate infection control should be established before soft tissue coverage. However, wounds infected by MDR do not heal well with this traditional method and there are no optimal treatment guidelines for MDR bacteria-contaminated wounds.We reviewed 203 patients who underwent vascularized flap surgery from 2012 to 2019 to cover wounds. Class IV and I wounds were compared according to the Centers for Disease Control and Prevention classification. Class IV was further classified as antibiotic-resistant (ARB) and antibiotic-sensitive (ASB) bacteria. Wound size, mode, location, pathogens, healing time, and basic demographics were evaluated. Data were compared using Cramer's V and one-way ANOVA or independent t tests.The average healing time was longer in the ARB (19.7 [range 7-44] days) and ASB (17.9 [range 2-36] days) groups than in the Clean group (16.5 [range 7-28] days). Healing time differed in the 3 groups (P = .036). It was longer in the class IV group than in the class I group (P = .01). However, it was not statistically different between the ARB and ASB groups (P = .164).In our study the difference in healing time was small when vascularized tissue transfer was done in ARB-infected wound compared with ASB-infected and clean wound. It is necessary to perform surgery using vascularized tissue for the infected wound of antibiotic-resistant bacteria., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

When patented, brand-name antibiotics lose market exclusivity, generics typically enter the market at lower prices, which may increase consumption of the drug. To examine the effect of generic market entry on antibiotic consumption in the United States, we conducted an interrupted time series analysis of the change in the number of prescriptions per month for antibiotics for which at least one generic entered the US market between 2000 and 2012. Data were acquired from the IQVIA Xponent database. Thirteen antibiotics were analyzed. Here, we show that one year after generic entry, the number of prescriptions increased for five antibiotics (5 to 406%)-aztreonam, cefpodoxime, ciprofloxacin, levofloxacin, ofloxacin-and decreased for one drug: cefdinir. These changes were sustained two years after. Cefprozil, cefuroxime axetil and clarithromycin had significant increases in trend, but no significant level changes. No consistent pattern for antibiotic use following generic entry in the United States was observed.

The gut bacterial community prevents many pathogens from colonizing the intestine. Previous studies have associated specific bacteria with clearing Clostridioides difficile colonization across different community perturbations. However, those bacteria alone have been unable to clear C. difficile colonization. To elucidate the changes necessary to clear colonization, we compared differences in bacterial abundance between communities able and unable to clear C. difficile colonization. We treated mice with titrated doses of antibiotics prior to C. difficile challenge, resulting in no colonization, colonization and clearance, or persistent colonization. Previously, we observed that clindamycin-treated mice were susceptible to colonization but spontaneously cleared C. difficile Therefore, we investigated whether other antibiotics would show the same result. We found that reduced doses of cefoperazone and streptomycin permitted colonization and clearance of C. difficile Mice that cleared colonization had antibiotic-specific community changes and predicted interactions with C. difficile Clindamycin treatment led to a bloom in populations related to Enterobacteriaceae Clearance of C. difficile was concurrent with the reduction of those blooming populations and the restoration of community members related to the Porphyromonadaceae and Bacteroides Cefoperazone created a susceptible community characterized by drastic reductions in the community diversity and interactions and a sustained increase in the abundance of many facultative anaerobes. Lastly, clearance in streptomycin-treated mice was associated with the recovery of multiple members of the Porphyromonadaceae , with little overlap in the specific Porphyromonadaceae observed in the clindamycin treatment. Further elucidation of how C. difficile colonization is cleared from different gut bacterial communities will improve C. difficile infection treatments. IMPORTANCE The community of microorganisms, or microbiota, in our intestines prevents pathogens like C. difficile from colonizing and causing infection. However, antibiotics can disturb the gut microbiota, which allows C. difficile to colonize. C. difficile infections (CDI) are primarily treated with antibiotics, which frequently leads to recurrent infections because the microbiota has not yet returned to a resistant state. The recurrent infection cycle often ends when the fecal microbiota from a presumed resistant person is transplanted into the susceptible person. Although this treatment is highly effective, we do not understand the mechanism. We hope to improve the treatment of CDI through elucidating how the bacterial community eliminates CDI. We found that C. difficile colonized susceptible mice but was spontaneously eliminated in an antibiotic treatment-specific manner. These data indicate that each community had different requirements for clearing colonization. Understanding how different communities clear colonization will reveal targets to improve CDI treatments., (Copyright © 2021 Lesniak et al.)

Urethritis refers to inflammation of the urethra and is classified as gonococcal (caused by Neisseria gonorrhoeae) or nongonococcal in origin (most commonly caused by Chlamydia trachomatis, Mycoplasma genitalium, or Trichomonas vaginalis). The most common signs and symptoms include dysuria, mucopurulent urethral discharge, urethral discomfort, and erythema. Diagnostic criteria include typical signs, symptoms, or history of exposure in addition to mucopurulent discharge, Gram stain of urethral secretions showing at least two white blood cells per oil immersion field, first-void urinalysis showing at least 10 white blood cells per high-power field, or a positive leukocyte esterase result with first-void urine. First-line empiric treatment consists of ceftriaxone and doxycycline; however, the antibiotic regimen may be targeted to the isolated organism. Repeat testing is not recommended less than three weeks after treatment because false-positive results are possible during this time. Patients treated for a sexually transmitted infection should have repeat screening in three months, with shared decision-making about future screening intervals. Patients treated for urethritis should abstain from sex for seven days after the start of treatment, until their partners have been adequately treated, and until their symptoms have fully resolved.

We describe rapid spread of multidrug-resistant gram-negative bacteria among patients in dedicated coronavirus disease care units in a hospital in Maryland, USA, during May-June 2020. Critical illness, high antibiotic use, double occupancy of single rooms, and modified infection prevention practices were key contributing factors. Surveillance culturing aided in outbreak recognition and control.

Zoonotic transmission is likely a pathway for antibiotic resistance. Data from a randomized trial of pediatric antibiotic administration were secondarily evaluated to determine if poultry ownership was significantly associated with the presence of gut genetic antibiotic resistance determinants among 118 children in Burkina Faso. Antimicrobial resistance (AMR) determinants were classified using DNA sequencing. We measured the relationship between genetic resistance determinants and chicken ownership using a logistic regression model adjusted for confounding variables. Children in households reporting poultry ownership had four times the odds of tetracycline resistance determinants in the gut compared with those without household poultry (odds ratio [OR]: 4.08, 95% CI: 1.08-15.44, P = 0.04). There was no statistically significant difference found for other antibiotic classes. Understanding the origins of antibiotic resistance may help spur the development of interventions to combat the global AMR crisis.

Background: Caesarean section increases the risk of postpartum infection for women and prophylactic antibiotics have been shown to reduce the incidence; however, there are adverse effects. It is important to identify the most effective class of antibiotics to use and those with the least adverse effects.  OBJECTIVES: To determine, from the best available evidence, the balance of benefits and harms between different classes of antibiotic given prophylactically to women undergoing caesarean section, considering their effectiveness in reducing infectious complications for women and adverse effects on both mother and infant., Search Methods: For this 2020 update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (2 December 2019), and reference lists of retrieved studies., Selection Criteria: We included randomised controlled trials (RCTs) comparing different classes of prophylactic antibiotics given to women undergoing caesarean section.  RCTs published in abstract form were also included. We excluded trials that compared drugs with placebo or drugs within a specific class; these are assessed in other Cochrane Reviews. We excluded quasi-RCTs and cross-over trials. Cluster-RCTs were eligible for inclusion but none were identified., Data Collection and Analysis: Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. We assessed the certainty of the evidence using the GRADE approach., Main Results: We included 39 studies, with 33 providing data (8073 women). Thirty-two studies (7690 women) contributing data administered antibiotics systemically, while one study (383 women) used lavage and was analysed separately. We identified three main comparisons that addressed clinically important questions on antibiotics at caesarean section (all systemic administration), but we only found studies for one comparison, 'antistaphylococcal cephalosporins (1 st and 2 nd generation) versus broad spectrum penicillins plus betalactamase inhibitors'.   We found no studies for the following comparisons: 'antistaphylococcal cephalosporins (1 st and 2 nd generation) versus lincosamides' and 'antistaphylococcal cephalosporins (1 st and 2 nd generation) versus lincosamides plus aminoglycosides'. Twenty-seven studies (22 provided data) included comparisons of cephalosporins (only) versus penicillins (only). However for this update, we only pooled data relating to different sub-classes of penicillins and cephalosporins where they are known to have similar spectra of action against agents likely to cause infection at caesarean section. Eight trials, providing data on 1540 women, reported on our main comparison, 'antistaphylococcal cephalosporins (1 st and 2 nd generation) versus broad spectrum penicillins plus betalactamase inhibitors'. We found data on four other comparisons of cephalosporins (only) versus penicillins (only) using systemic administration: antistaphylococcal cephalosporins (1 st and 2 nd generation) versus non-antistaphylococcal penicillins (natural and broad spectrum) (9 studies, 3093 women); minimally antistaphylococcal cephalosporins (3 rd generation) versus non-antistaphylococcal penicillins (natural and broad spectrum) (4 studies, 854 women); minimally antistaphylococcal cephalosporins (3 rd generation) versus broad spectrum penicillins plus betalactamase inhibitors (2 studies, 865 women); and minimally antistaphylococcal cephalosporins (3rd generation) versus broad spectrum and antistaphylococcal penicillins (1 study, 200 women). For other comparisons of different classes of antibiotics, only a small number of trials provided data for each comparison, and in all but one case data were not pooled. For all comparisons, there was a lack of good quality data and important outcomes often included few women. Three of the studies that contributed data were undertaken with drug company funding, one was funded by the hospital, and for all other studies the funding source was not reported. Most of the studies were at unclear risk of selection bias, reporting bias and other biases, partly due to the inclusion of many older trials where trial reports did not provide sufficient methodological information. We undertook GRADE assessment on the only main comparison reported by the included studies, antistaphylococcal cephalosporins (1 st and 2 nd generation) versus broad spectrum penicillins plus betalactamase inhibitors, and the certainty ranged from low to very low, mostly due to concerns about risk of bias, wide confidence intervals (CI), and few events. In terms of the primary outcomes for our main comparison of 'antistaphylococcal cephalosporins (1 st and 2 nd generation) versus broad spectrum penicillins plus betalactamase inhibitors': only one small study reported sepsis, and there were too few events to identify clear differences between the drugs (risk ratio (RR) 2.37, 95% CI 0.10 to 56.41, 1 study, 75 women, very low-certainty evidence). There may be little or no difference between these antibiotics in preventing endometritis (RR 1.10; 95% CI 0.76 to 1.60, 7 studies, 1161 women; low-certainty evidence). None of the included studies reported on infant sepsis or infant oral thrush. For our secondary outcomes, we found there may be little or no difference between interventions for maternal fever (RR 1.07, 95% CI 0.65 to 1.75, 3 studies, 678 women; low-certainty evidence). We are uncertain of the effects on maternal: wound infection (RR 0.78, 95% CI 0.32 to 1.90, 4 studies, 543 women), urinary tract infection (average RR 0.64, 95% CI 0.11 to 3.73, 4 studies, 496 women), composite adverse effects (RR 0.96, 95% CI 0.09 to 10.50, 2 studies, 468 women), and skin rash (RR 1.08, 95% CI 0.28 to 4.1, 3 studies, 591 women) (all very low certainty evidence). Although maternal allergic reactions were reported by two studies, there were no events. There were no infant outcomes reported in the included studies. For the other comparisons, the results for most outcomes had wide CIs, few studies and few women included. None of the included trials reported on longer-term maternal outcomes, or on any infant outcomes., Authors' Conclusions: Based on the best currently available evidence, 'antistaphylococcal cephalosporins' and 'broad spectrum penicillins plus betalactamase inhibitors' may have similar efficacy at caesarean section when considering immediate postoperative infection, although we did not have clear evidence for several important outcomes. Most trials administered antibiotics at or after cord clamping, or post-operatively, so results may have limited applicability to current practice which generally favours administration prior to skin incision. We have no data on any infant outcomes, nor on late infections (up to 30 days) in the mother; these are important gaps in the evidence that warrant further research. Antimicrobial resistance is very important but more appropriately investigated by other trial designs., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Despite the unique physiology and metabolic pathways of microbiomes from cold environments providing key evolutionary insights and promising leads for discovering new bioactive compounds, cultivable bacteria entrapped in perennial ice from caves remained a largely unexplored life system. In this context, we obtained and characterized bacterial strains from 13,000-years old ice core of Scarisoara Ice Cave, providing first isolates from perennial ice accumulated in caves since Late Glacial, and first culture-based evidences of bacterial resistome and antimicrobial compounds production. The 68 bacterial isolates belonged to 4 phyla, 34 genera and 56 species, with 17 strains representing putative new taxa. The Gram-negative cave bacteria (Proteobacteria and Bacteroidetes) were more resistant to the great majority of antibiotic classes than the Gram-positive ones (Actinobacteria, Firmicutes). More than 50% of the strains exhibited high resistance to 17 classes of antibiotics. Some of the isolates inhibited the growth of clinically important Gram-positive and Gram-negative resistant strains and revealed metabolic features with applicative potential. The current report on bacterial strains from millennia-old cave ice revealed promising candidates for studying the evolution of environmental resistome and for obtaining new active biomolecules for fighting the antibiotics crisis, and valuable cold-active biocatalysts.

Background: The antibiotic resistance profile of Helicobacter pylori (H. pylori) is constantly changing. Up-to-date and reliable data for the effectiveness of first-line H. pylori treatment protocols are necessary to provide evidence-based best-practice guidelines., Objectives: To determine the effectiveness, compliance and safety of first-line treatment for H. pylori in Israel., Methods: An observational, prospective, multicenter study was conducted in tertiary referral centers in Israel, as part of the European registry on H. pylori management (Hp-EuReg). H. pylori-infected patients were included from 2013 to March 2020. Data collected included demographics, clinical data, diagnostic tests, previous eradication attempts, current treatment, compliance, adverse events, and treatment outcome result., Results: In total, 242 patients were registered, including 121 (50%) who received first-line therapy, 41% of these individuals received clarithromycin based triple therapy and 58.9% received a four-drug regimen. The overall effectiveness of first-line therapy was 85% and 86% by modified intention-to-treat and per protocol analyses, respectively. The effectiveness of both sequential and concomitant therapies was 100% while clarithromycin-based triple therapy achieved an eradication rate of 79%. Treatment eradication was higher among patients who received high dose proton pump inhibitor (PPI) compared to those treated with low dose PPI (100% vs. 81.5% respectively, P < 0.01). No difference in treatment effectiveness was found between 7-, 10-, and 14-day treatment., Conclusions: The effectiveness of clarithromycin-based triple therapy is suboptimal. First-line treatment of H. pylori infection should consist of four drugs, including high dose PPI, according to international guidelines.

Objective: The indiscriminate prescription of antibiotics has led to the emergence of resistance microbes worldwide. This study aimed to investigate the antibiotic prescribing practices amongst general dental practitioners and specialists in managing endodontic infections in the United Arab Emirates (UAE)., Design: General dental practitioners and specialists in the UAE were invited to participate in an online questionnaire survey which included questions on socio-demographics, practitioner's antibiotic prescribing preferences for various pulpal and periapical diseases, and their choice, in terms of the type, dose and duration of the antibiotic. The link to the survey questionnaire was sent to 250 invited dentists. Data were analyzed by descriptive statistics and chi-square tests for independence and level of significance was set at 0.05., Results: A total of 174 respondents participated in the survey (response rate = 70%). The respondents who prescribed antibiotics at least once a month were 38.5% while 17.2% did so, more than three times a week; amoxicillin 500 mg was the antibiotic of choice for patients not allergic to penicillin (43.7%), and in cases of penicillin allergies, erythromycin 500 mg (21.3%). There was a significant difference in the antibiotic prescribing practices of GDPs compared to endodontists and other specialties especially in clinical cases such as acute apical abscesses with swelling and moderate to severe pre-operative symptoms and retreatment of endodontic cases (p<0.05). Approximately, three quarters of the respondents (78.7%) did not prescribe a loading dose when prescribing antibiotics. About 15% respondents prescribed antibiotics to their patients if they were not accessible to patients due to a holiday/weekend., Conclusions: In general, the antibiotic prescribing practices of UAE dentists are congruent with the international norms. However, there were occasions of inappropriate prescriptions such as in patients with irreversible pulpitis, necrotic pulps with no systemic involvement and/or with sinus tracts., Competing Interests: The authors have declared no competing interests exist.

Approval by the US Food and Drug Administration (FDA) of a drug for a given indication is thought to reassure clinicians, other health care providers, and patients that substantial evidence of effectiveness exists for specific indicated populations (patients and diseases). This study examines whether FDA approval of certain antibiotics should be so reassuring for all patient populations identified in the FDA-approved labels. Specifically, this study compared patient populations covered by FDA-approved labels for 21 novel antibiotics approved between 1999 and 2018 to the patient exclusion and inclusion criteria of pivotal trials that supported those approvals. We found that every FDA-approved label for these antibiotics included at least one identifiable patient population that was explicitly excluded from enrolling in the supporting pivotal trials. Two antibiotics, bedaquiline and ceftazidime-avibactam, were approved for use in populations that were fully excluded from enrolling in registration trials., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Bacteriocins are ribosomally synthesized peptides with antibacterial activity against food-borne pathogenic bacteria that cause spoilage, possessing important potential for use as a natural preservative in the food industry. The novel bacteriocin BM1300 produced by Lactobacillus crustorum MN047 was identified after purification in this study. It displayed broad-spectrum antibacterial activity against some selected Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration (MIC) values of BM1300 against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 were 13.4 μg/mL and 6.7 μg/mL, respectively. Moreover, BM1300 showed excellent thermal (between 60 and 120 °C), pH (2-11), and chemical (Tween-40, Tween-80, Triton X-100, and EDTA) stabilities. Time-kill curves revealed that BM1300 exhibited bactericidal activity against S. aureus and E. coli. The scanning and transmission electron microscopy indicated that BM1300 acted by disrupting the cell membrane integrity and increasing cell membrane permeabilization of indicator bacteria. The disruption of cell membrane integrity caused by BM1300 was further demonstrated by the uptake of propidium iodide (PI) and the release of intracellular lactate dehydrogenase (LDH) and nucleic acid and proteins. Moreover, BM1300 affected cell cycle distribution to exert antibacterial activity collaboratively. Meanwhile, BM1300 inhibited the growth of S. aureus and E. coli of beef meat and improved the microbiological quality of beef meat. These findings place BM1300 as a potential biopreservative in the food industry.

Natural products serve as chemical blueprints for most antibiotics in clinical use. The evolutionary process by which these molecules arise is inherently accompanied by the co-evolution of resistance mechanisms that shorten the clinical lifetime of any given class of antibiotics 1 . Virginiamycin acetyltransferase (Vat) enzymes are resistance proteins that provide protection against streptogramins 2 , potent antibiotics against Gram-positive bacteria that inhibit the bacterial ribosome 3 . Owing to the challenge of selectively modifying the chemically complex, 23-membered macrocyclic scaffold of group A streptogramins, analogues that overcome the resistance conferred by Vat enzymes have not been previously developed 2 . Here we report the design, synthesis, and antibacterial evaluation of group A streptogramin antibiotics with extensive structural variability. Using cryo-electron microscopy and forcefield-based refinement, we characterize the binding of eight analogues to the bacterial ribosome at high resolution, revealing binding interactions that extend into the peptidyl tRNA-binding site and towards synergistic binders that occupy the nascent peptide exit tunnel. One of these analogues has excellent activity against several streptogramin-resistant strains of Staphylococcus aureus, exhibits decreased rates of acetylation in vitro, and is effective at lowering bacterial load in a mouse model of infection. Our results demonstrate that the combination of rational design and modular chemical synthesis can revitalize classes of antibiotics that are limited by naturally arising resistance mechanisms.

Although Pseudomonas aeruginosa (P. aeruginosa) can infect both animals and humans, there is a paucity of veterinary studies on antimicrobial resistance of P. aeruginosa in South Africa. Secondary data of canine clinical cases presented at the hospital from January 2007 to December 2013 was used. The following information was recorded: type of sample, the date of sampling and the antimicrobial susceptibility results. Frequencies, proportions and their 95% confidence intervals were calculated for all the categorical variables. In total, 155 P. aeruginosa isolates were identified and included in this study. All the isolates were resistant to at least one antimicrobial (AMR), while 92% were multi-drug resistant (MDR). Most isolates were resistant to lincomycin (98%), penicillin-G (96%), orbifloxacin (90%), trimethoprim-sulfamethoxazole (90%) and doxycycline (87%). A low proportion of isolates was resistant to imipenem (6%), tobramycin (12%), amikacin (16%) and gentamicin (18%). A high proportion of MDR-P. aeruginosa isolates was resistant to amoxycillin-clavulanic acid (99%), tylosin (99%), chloramphenicol (97%) and doxycycline (96%). Few (6%) of MDR-P. aeruginosa isolates were resistant to imipenem. Pseudomonas aeruginosa was associated with infections of various organ systems in this study. All P. aeruginosa isolates of P. aeruginosa exhibited resistance to β-lactams, fluoroquinolones and lincosamides. Clinicians at the hospital in question should consider these findings when treating infections associated with P. aeruginosa.

In this study, molecular topology was used to develop several discriminant equations capable of classifying compounds according to their antibacterial activity. Topological indices were used as structural descriptors and their relation to antibacterial activity was determined by applying linear discriminant analysis (LDA) on a group of quinolones and quinolone-like compounds. Four equations were constructed, named DF1, DF2, DF3, and DF4, all with good statistical parameters such as Fisher-Snedecor's F (over 25 in all cases), Wilk's lambda (below 0.36 in all cases) and percentage of correct classification (over 80% in all cases), which allows a reliable extrapolation prediction of antibacterial activity in any organic compound. From the four discriminant functions, it can be extracted that the presence of sp 3 carbons, ramifications, and secondary amine groups in a molecule enhance antibacterial activity, whereas the presence of 5-member rings, sp 2 carbons, and sp 2 oxygens hinder it. The results obtained clearly reveal the high efficiency of combining molecular topology with LDA for the prediction of antibacterial activity.

In 2019, a project designed to develop a system for measuring and comparing antibiotic usage in hospitals was launched in Korea. As part of this project, we developed a means to classify antibiotic usage in Korean hospitals using a modified Delphi method. In results, the following categories of antibiotic classification were accepted for use in Korean hospitals: 1) broad-spectrum antibacterial agents predominantly used for hospital-onset infections in adults, 2) broad-spectrum antibacterial agents predominantly used for community-acquired infections in adults, 3) antibacterial agents predominantly used for resistant gram-positive infections in adults, 4) narrow-spectrum beta-lactam agents in adults, 5) antibacterial agents predominantly used for extensive antibiotic resistant gram-negative bacteria in adults, and 6) total antibacterial agents., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Background: Many studies had shown that prophylactic use of antibiotics could significantly reduce the intracranial infection (ICI) rate of craniotomy. However, there has been no comparison of these antibiotics., Methods: An electronic database search was performed, from inception to June 102,020. Randomized controlled trials (RCT) using different intravenous antibiotics (IVA) against the ICIs after craniotomy were considered. The primary outcome was the incidence rates of ICIs. An indirect treatment comparison (ITC) was conducted to compare the protective effect among the diverse antibiotic prophylaxis to prevent ICIs after craniotomy. Risk of potential bias was assessed., Results: A total of 3214 patients after craniotomy in 11 studies were included, 159 patients experienced postoperative ICI, including 33 patients in the antibacterial group and 126 in the control group. The calculate results of meta-analysis showed that except fusidic acid, preoperative intravenous injection of cephalosporin, clindamycin, vancomycin, and penicillin can significantly reduce the incidence of ICI after craniotomy, and ITC showed there was no statistically significance difference in the rates of post craniotomy ICI between the various antibiotics., Conclusion: The current evidence shows that low-grade antibacterial drugs can be selected to prevent ICI after craniotomy, but this may be due to the limited number of studies per antibiotic. It still needs more high-quality, large sample RCT to confirm., Systemic Review Registration: PROSPERO CRD42019133369.

Background: Urinary tract infections are one of the most common reasons for prescribing antibiotics in primary care. Current guidelines recommend fosfomycin, nitrofurantoin, or trimethoprim - sulfamethoxazol as empiric first line antimicrobial agents in uncomplicated infections. However, there is evidence that the use of fluoroquinolones, which are no longer recommended, is still inappropriate high. We determined antibiotic prescription patterns, quality and factors affecting antibiotic prescriptions in urinary tract infections in primary care in Switzerland., Methods: From June 2017 to August 2018, we conducted a cross-sectional study in patients suffering from a urinary tract infection (UTI). Patient and general practitioners characteristics as well as antibiotic prescribing patterns were analysed., Results: Antibiotic prescribing patterns in 1.352 consecutively recruited patients, treated in 163 practices could be analysed. In 950 (84.7%) patients with an uncomplicated UTI the prescriptions were according to current guidelines and therefore rated as appropriate. Fluoroquinolones were prescribed in 13.8% and therefore rated as inappropriate. In multivariable analysis, the age of the general practitioner was associated with increasing odds of prescribing a not guideline recommended antibiotic therapy., Conclusions: We found a high degree of guideline conform antibiotic prescriptions in patients with an uncomplicated urinary tract infection in primary care in Switzerland. However, there is still a substantial use of fluoroquinolones in empiric therapy.

Background: Antimicrobial susceptibility testing (AST) is a cornerstone of infection management in cystic fibrosis. However, there is little evidence that AST predicts the clinical outcome of CF antimicrobial treatment. It has been suggested there is a need for careful consideration of current AST use by the CF community., Methods: We engaged a group of experts consisting of pulmonary (adult and pediatric) and infectious disease clinicians, microbiologists, and pharmacists representing a broad international experience. We conducted an iterative systematic survey (Delphi) to determine and quantify consensus regarding key questions facing CF clinicians in the use of respiratory culture results including what tests to order, when to obtain them, and how to act upon the results of the testing., Results: Consensus was reached for many questions but there was not universal agreement to the questions that were addressed. There were some differences with respect to cultures obtained for surveillance compared to when there is clinical worsening. Areas of general consensus include when and how respiratory cultures should be performed, what information should be reported, and when AST should be performed. A key finding is that clinical response to treatment is used to guide treatment decisions rather than AST results., Conclusions: Recommendations are presented regarding questions related to microbiology testing for patients with CF. We have also offered recommendations for priority research questions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 European Cystic Fibrosis Society. All rights reserved.)

A structured survey of the cystic fibrosis pathogens Achromobacter, Pandoraea and Ralstonia species from thirteen sentinel hospitals throughout England was undertaken by Public Health England. One isolate per patient of these genera collected from CF patients during the seven-month survey period in 2015 was requested from participating hospitals. Species-level identification was performed using nrdA/gyrB sequence cluster analysis, and genotyping by pulsed-field gel electrophoresis. In total, 176 isolates were included in the survey; 138 Achromobacter spp. (78.4%), 29 Pandoraea spp. (16.5%) and 9 Ralstonia spp. (5.1%). Novel Achromobacter and Pandoraea clusters were identified. High levels of antimicrobial resistance were found, particularly among Pandoraea isolates. Genotyping analysis revealed considerable diversity, however one geographically-widespread cluster of A. xylosoxidans isolates from six hospitals was found, in addition to two other clusters, both comprising isolates from two hospitals, either derived from the same region (A. xylosoxidans), or from hospitals within the same city (P. apista)., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Background: The overuse of antimicrobials in food animals and the subsequent contamination of the environment have been associated with development and spread of antimicrobial resistance. This review presents information on antimicrobial use, resistance and status of surveillance systems in food animals and the environment in Africa., Methods: Information was searched through PubMed, Google Scholar, Web of Science, and African Journal Online databases. Full-length original research and review articles on antimicrobial use, prevalence of AMR from Africa covering a period from 2005 to 2018 were examined. The articles were scrutinized to extract information on the antimicrobial use, resistance and surveillance systems., Results: A total of 200 articles were recovered. Of these, 176 studies were included in the review while 24 articles were excluded because they were not relevant to antimicrobial use and/or resistance in food animals and the environment. The percentage of farms using antimicrobials in animal production ranged from 77.6% in Nigeria to 100% in Tanzania, Cameroon, Zambia, Ghana and Egypt. The most antibiotics used were tetracycline, aminoglycoside and penicillin groups. The percentage of multi drug resistant isolates ranged from 20% in Nigeria to 100% in South Africa, Zimbabwe and Tunisia. In the environment, percentage of multi drug resistant isolates ranged from 33.3% in South Africa to 100% in Algeria. None of the countries documented national antimicrobial use and resistance surveillance system in animals., Conclusion: There is high level of antimicrobial use, especially tetracycline, aminoglycoside and penicillin in animal production systems in Africa. This is likely to escalate the already high prevalence of antimicrobial resistance and multi drug resistance in the continent. This, coupled with weak antimicrobial resistance surveillance systems in the region is a great concern to the animals, environment and humans as well.

Physically disrupting microorganism membranes to enable antibiotics to overcome resistance mechanisms that inhibit or excrete antibiotics has great potential for reducing antibiotic doses and rendering resistance mechanisms inert. We demonstrate the synergistic inactivation of a Gram-positive (Staphylococcus aureus) and two Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria by combining 222 30 kV/cm electric pulses (EPs) or 500 20 kV/cm EPs with 300-ns EP duration with various antibiotics with different mechanisms of action is demonstrated. Doses of antibiotics that produced no inactivation in 10 min of exposure in solution with bacteria induced several log reductions under the influence of nanosecond EPs. Combining 2 μg/L or 20 μg/mL of rifampicin with the 30 kV/cm EPs enhanced Staphylococcus aureus inactivation compared with EPs alone, while only a few of the other combinations demonstrated improvement. Combining 2 μg/L or 20 μg/mL of mupirocin or rifampicin with either EP train enhanced E. coli inactivation compared with EPs alone. Combining 2 μg/L or 20 μg/mL of erythromycin or vancomycin with the 30 kV/cm EPs enhanced E. coli inactivation compared with EPs alone. These results indicate that EPs can make Gram-positive antibiotics efficient for inactivating Gram-negative bacteria with future studies required to optimize EP parameters for other antibiotics and Gram-negative bacteria.

Antimicrobial resistance is a growing global health concern. Antimicrobial stewardship (AMS) curbs resistance rates by encouraging rational antimicrobial use. However, data on antimicrobial stewardship in developing countries is scarce. The objective of this study was to characterize antimicrobial use at the University Teaching Hospital (UTH) in Lusaka, Zambia as a guiding step in the development of an AMS program. This was a cross-sectional, observational study evaluating antimicrobial appropriateness and consumption in non-critically ill adult medicine patients admitted to UTH. Appropriateness was defined as a composite measure based upon daily chart review. Sixty percent (88/146) of all adult patients admitted to the general wards had at least one antimicrobial ordered and were included in this study. The most commonly treated infectious diseases were tuberculosis, pneumonia, and septicemia. Treatment of drug sensitive tuberculosis is standardized in a four-drug combination pill of rifampicin, isoniazid, pyrazinamide and ethambutol, therefore appropriateness of therapy was not further evaluated. The most common antimicrobials ordered were cefotaxime (n = 45), ceftriaxone (n = 28), and metronidazole (n = 14). Overall, 67% of antimicrobial orders were inappropriately prescribed to some extent, largely driven by incorrect dose or frequency in patients with renal dysfunction. Antimicrobial prescribing among hospitalized patients at UTH is common and there is room for optimization of a majority of antimicrobial orders. Availability of certain antimicrobials must be taken into consideration during AMS program development., Competing Interests: The authors have declared that no competing interests exist.

Dental caries is the most common oral disease. The bacteriological aetiology of dental caries promotes the use of antibiotics or antimicrobial agents to prevent this type of oral infectious disease. Antibiotics have been developed for more than 80 years since Fleming discovered penicillin in 1928, and systemic antibiotics have been used to treat dental caries for a long time. However, new types of antimicrobial agents have been developed to fight against dental caries. The purpose of this review is to focus on the application of systemic antibiotics and other antimicrobial agents with respect to their clinical use to date, including the history of their development, and their side effects, uses, structure types, and molecular mechanisms to promote a better understanding of the importance of microbial interactions in dental plaque and combinational treatments., Competing Interests: The authors confirm that this article content has no conflicts of interest., (Copyright © 2020 Wei Qiu et al.)

Stenotrophomonas maltophilia is difficult to treat due to the production of multiple intrinsic and acquired mechanisms of resistance. Trimethoprim-sulfamethoxazole (TMP-SMZ) and the fluoroquinolones have traditionally been considered the drugs of choice but are plagued by increasing resistance and adverse drug effects. The objective of this study was to evaluate the in vitro activities of 12 clinically relevant antimicrobials against clinical S. maltophilia isolates nonsusceptible to levofloxacin and/or TMP-SMZ. A diverse panel of 41 clinical S. maltophilia isolates collected through the SENTRY Antimicrobial Surveillance Program from 2008 to 2018 was evaluated against ceftazidime, ceftazidime-avibactam, chloramphenicol, delafloxacin, levofloxacin, moxifloxacin, eravacycline, minocycline, omadacycline, polymyxin B, and tigecycline. MICs were determined in triplicate via reference broth microdilution and interpreted according to CLSI guidelines where available. MIC distributions and susceptibilities were also compared across infection type, acquisition setting, and geographic origin. Susceptibilities to levofloxacin and TMP-SMZ were 29.3% and 36.6%, respectively. Minocycline displayed the highest susceptibility rate overall (92.7%) and the lowest MIC 90 value (4 mg/liter) of any of the 12 agents tested. Only 3 isolates were resistant to levofloxacin, TMP-SMZ, and minocycline. Polymyxin B and tigecycline were the second most active agents. No significant differences were observed in MIC distributions across the 3 strata evaluated. These data demonstrate that few antimicrobials, old or new, maintain reliable activity against resistant S. maltophilia The role of minocycline in the treatment of infections due to S. maltophilia warrants further clinical investigation given its potent in vitro activity and favorable adverse effect profile., (Copyright © 2020 American Society for Microbiology.)

The growing occurrence of multidrug-resistant (MDR) Salmonella enterica in poultry has been reported with public health concern worldwide. We reported, recently, the occurrence of Escherichia coli and Salmonella enterica serovars carrying clinically relevant resistance genes in dairy cattle farms in the Wakiso District, Uganda, highlighting an urgent need to monitor food-producing animal environments. Here, we present the prevalence, antimicrobial resistance, and sequence type of 51 Salmonella isolates recovered from 379 environmental samples from chicken farms in Uganda. Among the Salmonella isolates, 32/51 (62.7%) were resistant to at least one antimicrobial, and 10/51 (19.6%) displayed multiple drug resistance. Through PCR, five replicon plasmids were identified among chicken Salmonella isolates including IncFIIS 17/51 (33.3%), IncI1α 12/51 (23.5%), IncP 8/51 (15.7%), IncX1 8/51 (15.7%), and IncX2 1/51 (2.0%). In addition, we identified two additional replicons through WGS (Whole Genome Sequencing; ColpVC and IncFIB). A significant seasonal difference between chicken sampling periods was observed (p = 0.0017). We conclude that MDR Salmonella highlights the risks posed to animals and humans. Implementing a robust, integrated surveillance system will aid in monitoring MDR zoonotic threats., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Antibiotic misuse is the paramount factor for antibiotic resistance. Tamale Teaching Hospital (TTH), located in Ghana's Northern Region, is the biggest tertiary hospital in the Northern half of the country and consequently one of the biggest prescribers of antibiotics. Understanding the use of antibiotics in the TTH and providing information that could be inferred to develop strategies for antibiotic prescription is of extreme importance in this era of multiple and pan-resistant strains of pathogenic microorganisms., Methods: A cross-sectional study on the use of antibiotics at TTH in the Northern region of Ghana was performed. Data were collected by reviewing 10% of patients' files from January to June 2015 and then assessed for its appropriateness against the criteria based on the British National Formulary (BNF) 2015 and BNF children 2013-2014. Results were expressed in frequencies and percentages., Results: A total of 617 patients' records were included in this study. Up to 385 cases of different antibiotic misuse were found, comprising of 335 errors in prescriptions and 50 non-completed treatments. The most common prescription error was made on treatment duration (29.6%). The potential interactions were 16.7%., Conclusion: The study revealed a high burden of antibiotics misuse in TTH. This suggests a need for the development of an antibiotic stewardship programme for the hospital., Competing Interests: The authors declare no competing interests., (© Pilar Garcia-Vello et al.)

Introduction: Urinary tract infection is one of the commonest causes of childhood morbidity. Early diagnosis and appropriate choice of antimicrobials is essential. Hence, this study aims to identify the prevalence of Escherichia coli in childhood urinary tract infections., Methods: This was a hospital based descriptive cross-sectional study conducted in Nobel Medical College, Biratnagar over a period of one year. A total of 163 cases aged 1-15 years were included and clinical profile, laboratory reports including bacterial isolates in urine cultures and their sensitivity patterns were documented., Results: The prevalence of Escherichia coli is 45 (53.57%) C.I. Escherichia coli was the most common organism isolated in bacterial cultures followed by Klebsiella 12 (14.29%), Enterococcus 10 (11.90%). Urinary tract infection was common among females with male: female ratio of 1:2.3. Fever 152 (93.2%) and abdominal pain 113 (69.3%) were the most common presenting symptoms. Escherichia coli was found most sensitive to Nitrofurantoin 43 (95.5%) followed by Ciprofloxacin 41 (91.1%) and Amikacin 40 (88.8%)., Conclusions: Urinary tract infections in childhood require prompt attention and treatment to prevent significant morbidity and mortality. From this study it can be concluded that Escherichia coli is one of the most common isolates in urine culture and Aminoglycosides and Fluoroquinolones can be accepted as empirical treatment regimens for childhood Urinary tract infections.

Introduction: Lower respiratory tract infection is a common infection and accounts for a greater burden of disease worldwide. It is a great challenge to the clinician and still more, with increasing antimicrobial resistance. Its empirical treatment may vary according to the type of causative organisms. The objective of this study is to identify the pathogenic microorganisms and their antimicrobial susceptibility pattern from sputum sample., Methods: This descriptive cross-sectional study was conducted in KIST Medical College and Teaching Hospital from February 2015 to January 2016. Ethical approval was taken from institutional review committee prior to the study with reference no. 0051/2014/15. Data on culture and sensitivity of isolates from sputum samples were collected from the records of the hospital. Sample collection, processing, identification of microorganisms and antimicrobial susceptibility tests were performed according to the Clinical and Laboratory Standards Institute guidelines. All the data were tabulated in an Excel sheet and analyzed using SPSS version 20., Results: Out of 2318 samples, 694 (29.93%) sputum samples at 95% confidence interval (737.21- 650.79) were reported as culture positive. Klebsiella was the most common isolate followed by Pseudomonas, Escherichia coli, Acinetobacter, Staphylococcus aureus, Candida albicans, Streptococcus pneumoniae, Streptococcus pyogenes, and others. Imipenem and vancomycin showed the most sensitivity towards gram-negative and gram-positive bacteria respectively., Conclusions: Proper diagnosis, identification of causative agents and their antimicrobial susceptibility pattern are important steps to limit the irrational use of antimicrobials. Prescribing antimicrobials empirically in the case of suspected lower respiratory tract infection is difficult.

Purpose: Fluoroquinolone antibiotics are associated with rare, but severe adverse events. They are frequently used for the treatment of acute exacerbations of COPD (AECOPD). While their effectiveness in severe exacerbations requiring hospitalisation has been well documented, the potential benefit in the ambulatory setting is less clear, especially in uncomplicated patients with COPD., Patients and Characteristics: We carried out a retrospective cohort study using health care databases from six Canadian provinces in subjects visiting their physician for uncomplicated COPD. Subjects dispensed either a quinolone or other antibiotics were compared using inverse probability of treatment weights with high dimensional propensity scores on 30-day outcomes, including repeat visits, hospitalisation for AECOPD and subsequent antibiotic prescription. Results from each province were combined by random effects meta-analysis., Results: We identified 286,866 AECOPD events among 203,642 unique individuals. The frequency of fluoroquinolone use, mostly levofloxacin and moxifloxacin, varied by province and ranged from 8% to 32% of AECOPD antibiotic prescriptions. The risk of a repeat ambulatory care visit was increased among patients who were dispensed a fluoroquinolone compared with other antibiotics (OR 1.32, 95% CI 1.27-1.36). The risk of a hospitalisation for AECOPD was also higher with fluoroquinolones (OR 1.52, 95% CI 1.33-1.74). There was no difference in subsequent antibiotic prescriptions (OR 1.00, 95% CI 0.94-1.07)., Conclusion: There is no apparent benefit in short-term outcomes with fluoroquinolones as compared to other antibiotics for the ambulatory treatment of AECOPD in uncomplicated patients. These findings support current recommendations that fluoroquinolones be reserved for AECOPD in patients with recurrent exacerbations, significant co-morbidity or requiring hospitalisation., Competing Interests: Dr Ingrid Sketris reports salary support in part from CIHR for the CNODES project, during the conduct of the study, grants from Nova Scotia Government’s Drug Evaluation Alliance of Nova Scotia, CIHR, and Australian NHMRC, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2019 Ernst et al.)

Pneumonia is one of the leading causes of death in older people, with high mortality rates (> 80%). One of the bacterial pathogens causing pneumonia is Staphylococcus aureus. The unique adaptive ability of S. aureus to a broad range of antibiotics has led to the emergence of methicillin-resistant S. aureus (MRSA) strain. MRSA pneumonia remains a relatively uncommon infection in older people, but it is associated with a very high mortality rate. We report two cases of MRSA pneumonia that highlight the severe clinical presentation and virulence of MRSA infections in geriatric population. MRSA pneumonia can present with mostly an uncontrollable clinical evolution and an infaust prognosis. Therefore, clinicians should be aware of MRSA pneumonia in patients with comorbidities, recent hospitalization with antibiotic treatment, previous MRSA infections and also in patients residing in nursing homes/revalidation centers. Low prevalence of MRSA combined with a lack of highly distinctive clinical features makes accurate targeting of empirical treatment with antibiotics very difficult. Currently, monotherapy with linezolid or vancomycin remain the first choice, in adult patients with proven MRSA infection. Despite the higher age related mortality rates, there are no specific treatment guidelines for older patients.

Background:  A patient presenting with fever and purpura after a stay in the tropics tempts a physician to make a differential diagnosis mainly focusing on imported diseases. Although the importance of considering a tropical disease is obvious, the fact that cosmopolitan infections account for one third of the cases in a febrile returning traveler must not be overseen. Toxic Shock Syndrome is amongst the most notorious diseases due to the high mortality when inappropriately managed and the association with necrotizing fasciitis. Methods  : We present a 60-year old female with fever, shock syndrome and progressive appearance of painful purpura on the lower legs after a 2-week holiday in Zanzibar. Results  : The patient was diagnosed with Streptococcal Toxic Shock Syndrome. Treatment focusing on aggressive fluid resuscitation, prompt administration of antibiotics (ceftriaxon, doxycycline and one dose of amikacin) and adjunctive treatment by clindamycin and immunoglobulin was initiated. She was also immediately taken into surgery for a bilateral fasciotomy and surgical exploration of the lower legs. Histology appeared compatible with purpura fulminans, thereby excluding necrotizing fasciitis. No source of infection could be identified.  Conclusion : Toxic Shock Syndrome remains a challenging diagnosis and even more in a returning traveler with an extensive differential diagnosis containing both tropical and cosmopolitan diseases. Cornerstones for the treatment of Streptococcal Toxic Shock Syndrome are abrupt administration of antimicrobial therapy comprising beta-lactam antibiotics and clindamycin and surgical exploration to apply source control when indicated.

Case report : We present a case of a 66-year-old female diagnosed with  R. gnavus  bacteremia associated with fecal peritonits secondary to small-bowel herniation and perforation. Identification  as  R. gnavus  was delayed because of absence of this species in the MALDI-TOF MS database (Vitek MS, bioMérieux). Identification was provided by 16S rRNA gene sequencing. Review :  R. gnavus,  a Gram-positive, strictly anaerobic bacterium, is a member of the human gut microbiota. Dysbiosis in the gut microbiota, with increased amounts of  R. gnavus,  has been described in inflammatory bowel disease.  R. gnavus  has only been reported occasionally as the cause of infections. Hence the potential pathogenicity is not yet fully recognized, and data regarding the antimicrobial susceptibility profile are rare. Identification of anaerobic bacteria such as  R. gnavus  is greatly accelerated  as a result of the introduction of MALDI-TOF MS. However, as illustrated in this case report, an extensive and up-to-date MALDI-TOF MS database is necessary for providing an accurate identification.

We previously reported the distribution of Achromobacter spp. (species and Sequence Types (ST)) in our French Cystic Fibrosis (CF) centre. In the present study we collected 109 Achromobacter isolates (1/patient) from 9 other French CF Centres for species identification, antimicrobial susceptibility testings and Multilocus-Sequence-Typing (MLST) analysis. Ten species were detected, A. xylosoxidans being the most predominant one (73.4% of the isolates). Piperacillin-tazobactam, ceftazidime, imipenem, meropenem and ciprofloxacin were respectively active against 88, 70, 79, 72 and 23% of the isolates. Among the 79 A. xylosoxidans isolates, 46 STs were detected. Interestingly, ST 137, recovered in 4 centres (5 patients), was previously detected in our centre (2 patients). The strains from the 7 patients belonged to the same pulsotype (pulsed-field-gel-electrophoresis analysis) and harboured acquired resistance to meropenem, ceftazidime, ciprofloxacin, and except for 2 isolates, to imipenem and piperacillin-tazobactam. This is the first description in France of a circulating multiresistant A. xylosoxidans strain., (Copyright © 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Most international guidelines recommend empirical therapy for community-acquired pneumonia (CAP) to be based on site of care. Some patients with severe CAP are managed in general wards because of limited intensive care unit (ICU) bed or because of unrecognition of the pneumonia severity. Appropriate initial antibiotic treatment for severe CAP outside ICU has not yet been established. This study aimed to determine the prevalence and the impact of initial antibiotic selection on the outcomes of patients with severe CAP who were admitted and managing in general wards., Methods: This prospective observational study included consecutive patients hospitalized for presumed CAP in general wards over a 1-year period. Severe CAP was identified using the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) criteria. Initial antibiotic treatment in the first 24 h were collected. The primary outcome was the rate of unfavorable outcome (composite outcome of treatment failure and in-hospital death). The secondary outcome was the number of hospital-free days assessed 30 days after enrollment into the study., Results: There were 94 patients hospitalized with CAP of which 50 (53.2%) patients were compatible with severe CAP. An etiologic diagnosis was found in 43 (45.8%) patients. The most common pathogens identified in patients with severe CAP were Staphylococcus aureus (28.6%) and Klebsiella pneumoniae (28.6%), followed by Pseudomonas aeruginosa (17.9%). Patients with severe CAP had significantly more positive blood culture than patients with non-severe CAP (24% VS 4.5%; p = .008). Initial antibiotic treatment were discordant with the IDSA/ATS guidelines in 42% of all patients hospitalized with CAP, and 52% of patients with severe CAP. Multivariate analysis revealed that age (OR 1.1, 95% CI 1.01-1.1) and initial antibiotic treatment discordant to guidelines for severe CAP in ICU (OR 4.6, 95% CI 1.3-17.1) were independent risk factors of the unfavorable outcome of patients with severe CAP. Patients with unfavorable outcome had lower number of hospital-free days than patients with favorable outcome (5.2 ± 8 days VS 18 ± 7.1 days; p < .001)., Conclusions: Patients with severe CAP outside ICU should be recognized for appropriate initial antibiotic selection to improve outcomes.

Introduction: Daptomycin, macrolides, trimethoprim-sulfamethoxazole, linezolid, fluoroquinolones, and cefdinir are known to be associated with rhabdomyolysis. Other antibiotics may also lead to rhabdomyolysis, but no study has systemically compared rhabdomyolysis associations for many available antibiotics. Objectives: The objective of this study was to evaluate the association between rhabdomyolysis and many available antibiotics using the FDA Adverse Event Report System (FAERS). Methods: FAERS reports from January 1, 2004 to December 31, 2017 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify rhabdomyolysis cases. Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) for the association between antibiotics and rhabdomyolysis were calculated. An association was considered statistically significant when the lower limit of the 95%CI was greater than 1.0. Results: A total of 2,334,959 reports (including 7,685 rhabdomyolysis reports) were considered, after inclusion criteria were applied. Daptomycin had the greatest proportion of rhabdomyolysis reports, representing 5.5% of all daptomycin reports. Statistically significant rhabdomyolysis RORs (95% CI) for antibiotics were (in descending order): daptomycin 17.94 (14.08-22.85), cefditoren 8.61 (3.54-20.94), cefaclor 7.16 (2.28-22.49), erythromycin 5.93 (3.17-11.10), norfloxacin 4.50 (1.44-14.07), clarithromycin 3.95 (2.77-5.64), meropenem 3.19 (1.51-6.72), azithromycin 2.94 (1.96-4.39), cefdinir 2.84 (1.06-7.62), piperacillin-tazobactam 2.61 (1.48-4.61), trimethoprim-sulfamethoxazole 2.53 (1.52-4.21), linezolid 2.49 (1.47-4.21), ciprofloxacin 2.10 (1.51-2.92). Conclusions: This study confirms prior evidence for rhabdomyolysis associations with daptomycin, macrolides, trimethoprim-sulfamethoxazole, linezolid, fluoroquinolones, and cefdinir. This study also identifies previously unknown rhabdomyolysis associations with meropenem, cefditoren, cefaclor, and piperacillin-tazobactam., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The over-use of antibiotics has been identified as a major global challenge, where there is insufficient knowledge about the use of antibiotics in primary healthcare settings, especially at a population level. This study aims to investigate the trends and patterns of antibiotic sales in primary care in Hubei, China over a six-year period from 2012 to 2017. Antibiotic sales were expressed with Defined Daily Doses per 1000 inhabitants per day (DIDs) and compared with European countries using the 12 quality indicators proposed by the scientific advisory board of the European Surveillance of Antimicrobial Consumption (ESAC) project. Antibiotic sales increased from 12.8 DID in 2012 to 15.3 DID in 2013, and then declined afterwards. The most commonly used antibiotics, J01C (beta-lactam antimicrobials, penicillins), accounted for 40.5% of total antibiotic sales. Parenteral administration of antibiotics accounted for over 50% of total antibiotic sales. Total antibiotic sales were almost on a par with the 31 European countries monitored by the ESAC project, but cephalosporin sales were higher than at least three quarters of the compared countries, resulting in a significant higher proportion of third-generation cephalosporin consumption (13.8-19.43%). The relative consumption of Fluoroquinolone (9.26-9.89%) was also higher than at least half of the compared countries. There is a lack of robust evidence to show that antibiotic consumption in primary care is lower in Hubei compared with other countries. The preference of clinicians in China to use broad-spectrum and parenteral antibiotics deserves further study and policy attention.

Introduction: Aeromonas is a common cause of gastroenteritis but occasionally it can cause extraintestinal infections. The incidence of bacteremia by this genus is very low and in general the patients have associated base diseases., Materials and Methods: Retrospective analysis of episodes of bacteremia by Aeromonas spp. during a period of eight years in the National Hospital of Clinics of the city of Córdoba, emphasizing age, sex, associated comorbidities, clinical presentation, focus, origin of the infection, clinical evolution, species prevalence and antimicrobial sensitivity of the same ., Results: 10 episodes of bacteremia were recorded by Aeromonas spp. 60% corresponded to women and 40% to men. The average age was 65 years. In seven patients the origin of the infection was community and in three nosocomial. 70% of the patients presented predisposing base pathologies. The focus of bacteremia was abdominal in two cases. A. hydrophila complex was responsible for 50% of the cases. 80% of bacteremia were monomicrobial. The isolates generally showed high percentages of sensitivity., Conclusion: Bacteremia occurred in elderly patients of both sexes, most of whom had associated comorbidities. The majority of the infections originated in the community. While bacteremia by Aeromonas spp. it is rare, the mortality found in our study was relatively high despite the high percentage of sensitivity to antimicrobials., (Universidad Nacional de Córdoba)

Aims: Cardiac implantable electronic device (CIED) infection rates are increasing. Worldwide compliance and disparities to published guidelines for the prevention, diagnosis and management of these conditions are not well elucidated. The purpose of this survey, therefore, was to clarify these issues through an inquiry to arrhythmia-related associations and societies worldwide., Methods and Results: A questionnaire comprising 15 questions related to CIED infections was distributed among members of seven arrhythmia societies worldwide. A total of 234 centres in 62 countries reported implantation rates of which 159 (68.0%) performed more than 200 device implantations per year and 14 (6.0%) performed fewer than 50 implantations per year. The reported rates of CIED infections for 2017 were ≤2% in 78.7% of the centres, while the infection rates exceeded 5% in 7.8% of the centres. Preventive measures for CIED infection differed from published recommendations and varied among different regions mainly in terms of pocket irrigation and administering post-operative antimicrobial therapy the use of which was reported by 39.9% and 44% of the respondents, respectively. Antibacterial envelopes were used by 37.7% of the respondents in selected circumstances. In terms of pocket infection management, 62% of the respondents applied complete system removal as an initial step. Diagnostic pocket needle aspiration and pocket surgical debridement were reported by 15.8% and 11.8% of centres, respectively., Conclusion: Clinical practices for prevention and management of CIED do not fully comply with current recommendations and demonstrate considerable regional disparities. Further education and programmes for improved implementation of guidelines are mandatory., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objectives: Group B Streptococcus (GBS) is an important opportunistic bacteria that causes a wide range of infections including neonatal sepsis, meningitis, pneumonia, soft tissue and urinary tract infections (UTI). The aim of this study was to evaluate the antimicrobial susceptibility patterns, surface proteins and capsular types of GBS isolates., Results: 100 of UTI isolates were confirmed as GBS. Antimicrobial susceptibility pattern showed that 95% of GBS isolates were resistant to tetracycline, followed by erythromycin (52%), clindamycin (47%), levofloxacin (9%) and penicillin, cefepime, cefotaxime, and ceftriaxone each with (8%), and vancomycin 1%. Common capsular types were III, Ib, V, II, Ia and IV respectively and the distribution of surface protein genes was as follows: rib (40%), alpha-c (22%), alp2/3 (18%) and epsilon (15%), and alp4 gene was not detected in the isolates. Our findings showed the relationship between capsular types with Alpha-like proteins, as well as reduced sensitivity to antibiotics, so the performance of antibiotic surveillance programs is recommended.

Question: Is broad-spectrum antibiotic use associated with poor outcomes in community-onset pneumonia after adjusting for confounders?, Methods: We performed a retrospective, observational cohort study of 1995 adults with pneumonia admitted from four US hospital emergency departments. We used multivariable regressions to investigate the effect of broad-spectrum antibiotics on 30-day mortality, length of stay, cost and Clostridioides difficile infection (CDI). To address indication bias, we developed a propensity score using multilevel (individual provider) generalised linear mixed models to perform inverse-probability of treatment weighting (IPTW) to estimate the average treatment effect in the treated. We also manually reviewed a sample of mortality cases for antibiotic-associated adverse events., Results: 39.7% of patients received broad-spectrum antibiotics, but drug-resistant pathogens were recovered in only 3%. Broad-spectrum antibiotics were associated with increased mortality in both the unweighted multivariable model (OR 3.8, 95% CI 2.5-5.9; p<0.001) and IPTW analysis (OR 4.6, 95% CI 2.9-7.5; p<0.001). Broad-spectrum antibiotic use by either analysis was also associated with longer hospital stay, greater cost and increased CDI. Healthcare-associated pneumonia was not associated with mortality independent of broad-spectrum antibiotic use. In manual review we identified antibiotic-associated events in 17.5% of mortality cases., Conclusion: Broad-spectrum antibiotics appear to be associated with increased mortality and other poor outcomes in community-onset pneumonia., Competing Interests: Conflict of interest: B.J. Webb reports research support from Astellas Pharma, Inc. unrelated to this study and speaking honorarium from BioFire Diagnostics. Conflict of interest: J. Sorensen has nothing to disclose. Conflict of interest: A. Jephson has nothing to disclose. Conflict of interest: I. Mecham has nothing to disclose. Conflict of interest: N.C. Dean has nothing to disclose., (Copyright ©ERS 2019.)

Introduction: Plant products are sources for drug development against multidrug resistant bacteria., Methods: The antimicrobial activity of Origanum vulgare L. essential oil (OVeo) against carbapenem-resistant strains was assessed by disk-diffusion, microdilution (REMA-Resazurin Microtiter Assay), and time kill assays., Results: Carbapenemase production was confirmed for all strains. OVeo exhibited a minimum inhibitory concentration of 0.059% v/v for Klebsiella pneumoniae and Serratia marcescens, and of 0.015 % v/v for Acinetobacter baumannii. A decrease in cell count was observed after a 4 h treatment., Conclusions: OVeo antimicrobial effect was rapid and consistent, making it a candidate for developing alternative therapeutic options against carbapenem-resistant strains.