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Background: The WHO Model List of Essential Medicines classified antibiotics into Access, Watch, and Reserve (AWaRe) categories for the treatment of 31 priority bacterial infections as a tool to facilitate antibiotic stewardship and optimal use. We compared the listing of antibiotics on national essential medicines lists (NEMLs) to those in the 2019 WHO Model List and the AWaRe classification database to determine the degree to which NEMLs are in alignment with the AWaRe classification framework recommended by WHO., Methods: In this cross-sectional study, we obtained up-to-date (data after 2017) NEMLs from our Global Essential Medicines (GEM) database, WHO online resources, and individual countries' websites. From the 2019 WHO Model List we extracted, as a reference standard, a list of 37 antibiotics (44 unique antibiotics after accounting for combination drugs or therapeutically equivalent drugs as specified by WHO) that were considered essential in treating 31 of the most common and severe clinical infectious syndromes (priority infections). From the WHO AWaRe Classification Database, which contains commonly used antibiotics globally, we extracted a list of 122 AWaRe antibiotics listed by at least one country in the GEM database. We then assessed individual countries' NEMLs for listing of the 44 essential and 122 commonly used antibiotics, overall and according to AWaRe classification group. We also evaluated and summarised the listing of both first-choice and second-choice treatments for the 31 priority infections. A total coverage score was calculated for each country by assigning a treatment score of 0-3 for each priority infection on the basis of whether first-choice and second-choice treatments, according to the 2019 WHO Model List, were included in the country's NEML. Coverage scores were then compared against the score of the 2019 WHO Model List and across World Bank income groups and WHO regions., Findings: As of July 7, 2020, we had up-to-date NEMLs for 138 countries. Of the 44 unique essential antibiotics, 24 were Access, 15 were Watch, and five were Reserve. The median number of total essential antibiotics listed across the 138 NEMLs was 26 (IQR 21-32). 102 (74%) countries listed at least 22 (50%) of the 44 essential antibiotics. The median number of total AWaRe antibiotics listed by the 138 countries was 35 (IQR 29-46), of Access antibiotics was 18 (16-21), of Watch antibiotics was 16 (11-22), and of Reserve antibiotics was one (0-2). 56 (41%) countries did not list any essential Reserve antibiotics. 131 (95%) countries had coverage scores of at least 60, equivalent to at least 75% of the score of the 2019 WHO Model List, which was 80. Nine (7%) countries listed fewer than 12 of 24 essential Access antibiotics, and seven (5%) did not list sufficient first-choice and second-choice treatments for priority infections (ie, they had coverage scores lower than 60). Of the 31 priority infections, acute neonatal meningitis and high-risk febrile neutropenia did not have enough listed treatments, with 82 (59%) countries listing no treatment for acute neonatal meningitis and 84 (61%) countries listing only a first-choice treatment, only a second-choice treatment, or no treatment for high-risk febrile neutropenia. Coverage scores differed between countries on the basis of World Bank income groups (p=0·025)., Interpretation: Our findings highlight potential changes to the antibiotics included in NEMLs that would increase adherence to international guidance aimed at effectively treating infectious diseases while addressing antimicrobial resistance., Funding: Canadian Institutes of Health Research and Ontario Strategy for Patient Oriented Research Support Unit., Competing Interests: Declaration of interests NP reports grants from Canadian Institutes of Health Research and Ontario Strategy for Patient Oriented Research Support Unit, during the conduct of the study. ML reports grants and personal fees from WHO and Sunovion Pharmaceuticals, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.)

Antibiotic resistance is a global threat that should be urgently resolved. Finding a new antibiotic is one way, whereas the repression of the dissemination of virulent pathogenic bacteria is another. From this point of view, this paper summarizes first the mechanisms of conjugation and transformation, two important processes of horizontal gene transfer, and then discusses the approaches for disarming virulent pathogenic bacteria, that is, virulence factor inhibitors. In contrast to antibiotics, anti-virulence drugs do not impose a high selective pressure on a bacterial population, and repress the dissemination of antibiotic resistance and virulence genes. Disarmed virulence factors make virulent pathogens avirulent bacteria or pathobionts, so that we human will be able to coexist with these disarmed bacteria peacefully.

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.)

Background: Antimicrobial use (AU) of antipseudomonal β-lactams (APBL) has significantly increased over the past decade in US hospitals. This retrospective cohort study compares 2 common antimicrobial stewardship strategies, syndrome-specific interventions and antimicrobial postprescription prospective audit and feedback (PAF), in reducing AU of APBL at a large community-teaching hospital., Methods: Four antimicrobial stewardship interventions targeting APBL were serially introduced, including 2 syndrome-specific interventions (bloodstream and intra-abdominal infections) and 2 PAF interventions (carbapenems and piperacillin/tazobactam). Multivariable linear regression was used to examine overall AU of APBL and audited antimicrobial agents., Results: Overall AU of APBL declined from 92.4-69.1 days of therapy (DOT) per 1,000 patient-days between February 2013 and July 2017 (P < .001). Both syndrome-specific interventions were associated with significant reduction in AU of APBL (-7.7 [95% confidence interval (CI): -11.5, -4.0] and -6.0 [95% CI: -9.7, -2.3] DOT per 1,000 patient-days) for bloodstream and intra-abdominal infections, respectively). No significant change in overall AU of APBL was observed after implementation of PAF interventions for carbapenems (-1.4 [95% CI: -7.4, 4.6] DOT per 1,000 patient-days) or piperacillin/tazobactam (0.9 [95% CI: -3.7, 5.4] DOT per 1,000 patient-days)., Conclusions: Implementation of syndrome-specific interventions was followed by significant reduction in AU of APBL in this population. Despite reducing AU of targeted agents, neither PAF intervention contributed to overall observed decline in APBL use, likely due to compensatory increase in using other APBL., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the epidemiology and healthcare factors associated with late-onset neonatal enterococcal infections., Design: Multicentre, multinational retrospective cohort study using prospectively collected infection data from a neonatal infection surveillance network between 2004 and 2016; this was supplemented with healthcare data from a questionnaire distributed to participating neonatal units., Setting: Sixty neonatal units across Europe (UK, Greece, Estonia) and Australia., Patients: Infants admitted to participating neonatal units who had a positive culture of blood, cerebrospinal fluid or urine after 48 hours of life., Results: In total, 414 episodes of invasive Enterococcus spp infection were reported in 388 infants (10.1% of a total 4083 episodes in 3602 infants). Enterococcus spp were the second most common cause of late-onset infection after coagulase-negative Staphylococcus spp and were strongly associated with necrotising enterocolitis (NEC) (adjusted OR 1.44, 95% CI 1.02 to 2.03, p=0.038), total parenteral nutrition (TPN) (adjusted OR 1.34, 95% CI 1.06 to 1.70, p=0.016), increasing postnatal age (per 1-week increase: adjusted OR 1.04, 95% CI 1.02 to 1.06, p<0.001) and decreasing birth weight (per 1 kg increase: adjusted OR 0.85, 95% CI 0.74 to 0.97, p=0.017). There was no evidence that inadequate nurse to patient staffing ratios in high-dependency units were associated with a higher risk of enterococcal infections., Conclusions: Enterococcus spp were the second most frequent cause of late-onset infections. The association between enterococcal infections, NEC and TPN may inform empiric antimicrobial regimens in these contexts and provide insights into reducing these infections., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Debate about antimicrobial resistance (AMR) in animals and the impact on humans is often inappropriately focussed on the crude amount of antimicrobials used in animals without deference to issues of 'intensity of use', 'quality of use' and especially the class of agents being administered. In the latter case, tools for helping to manage how the use of specific antimicrobial agents impact on the risk and consequences of antimicrobial resistance in humans have been available for almost two decades. These consist of antimicrobial ratings systems, which formally define the importance of each individual agent in human health by assigning them to a position on a graduated scale of 'importance' comprising up to four categories of risk. Until recently, these published ratings have only had a modest impact on antimicrobial stewardship at the frontline of medical and veterinary practice, although they will undoubtedly have a substantial influence into the future. This article considers the evolution of the available 'antimicrobial ratings systems' applicable to Australian and international settings and their pivotal future-role in the educating of animal managers, policy makers and prescribers. Faithful application of these rating systems at all levels of decision making to do with antimicrobial use is now seen as central to the protection of animals, humans and economies from the scourge of AMR., (© 2019 State of New South Wales.)

Central nervous system (CNS) infections are associated with high mortality rates. The clinical presentation of many CNS infections by different pathogens is difficult to distinguish, but the definite diagnosis of the etiology is critical for effective therapy and prognosis. The aim of this study was to explore the etiology of CNS infections with definite diagnoses based on data from a clinical microbiology laboratory in Tongji Hospital, a teaching hospital in China, obtained over a six-year period. We conducted a retrospective study on all cerebrospinal fluid (CSF) specimens submitted to our clinical microbiology laboratory from September, 2012 to December, 2018. The etiology of CNS infections caused by Cryptococcus neoformans, Mycobacterium tuberculosis and common bacteria was analyzed. Antimicrobial susceptibility testing was conducted on all isolates. The results showed that 1972 cases of CNS infections were identified from 18 300 CSF specimens. Common bacterial meningitis (BM), cryptococcal meningitis (CM) and tuberculous meningitis (TM) accounted for 86.3% (677/785), 9.4% (74/785) and 4.3% (34/785) respectively of cases over the six-year period. BM was the most common among the different age groups, followed by CM. Of the TM cases, 44.1% (15/34) were distributed within the age group of 15-34 years, whereas for CM cases, 52.7% (39/74) occurred within the 35-54-year age group, and the age distribution of BM cases was fairly even. Among the bacterial pathogens isolated, Staphylococcus epidermidis was the most common, accounting for 12.5% (98/785), followed by Acinetobacter baumannii (ABA) and Staphylococcus aureus (SAU), accounting for 11.8% (93/785) and 7.6% (60/785) respectively. The resistance rates to antibiotics were >75%, with the exception of the resistance rate of ABA to tegafycline, which was <3%. More than 60% of SAU strains displayed resistance to penicillin, oxacillin, ampicillin/sulbactam, cefazolin, cefuroxime, gentamycin, tobramycin, erythromycin and levofloxacin, whereas more than 90% of SAU strains showed susceptibility to trimethoprim/sulfamethoxazole, tegafycline, vancomycin, teicoplanin and linezolid. For C. neoformans, the susceptibility rates to amphotericin B, 5-fluorocytosine, fluconazol and voriconazole were >95%. Analysis of samples from patients with CNS infection in a clinical microbiology laboratory at a teaching hospital in China over a six-year period indicated that the most common etiological agents were the bacteria ABA and SAU. The antibiotic resistance levels of ABA were found to be high and of concern, whereas isolates of C. neoformans were found to be sensitive to antifungal antibiotics.

Objective: To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability, dosage, and administration of omadacycline, a new tetracycline antibiotic., Data Sources: A literature search through PubMed, Google Scholar, and clinicaltrials.gov was conducted (2008 to October 2018) using the search terms omadacycline and PTK-0796. Abstracts presented at recent conferences, prescribing information and information from the FDA and the manufacturer's website were reviewed., Study Selection and Data Extraction: Preclinical data and published phase 1, 2, and 3 studies were evaluated., Data Synthesis: Omadacycline displays in vitro activity against a wide range of bacteria. Clinical trials have shown that omadacycline is noninferior to linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia (CABP). A loading dose of 200 mg intravenously (IV) once or 100 mg IV twice or 450 mg orally once is recommended followed by a maintenance dose of 100 mg IV or 300 mg orally once daily. No dosage adjustment is needed in patients with renal or hepatic impairment. Omadacycline is well tolerated, with nausea being a common adverse effect, but is associated with food and drug interactions. Relevance to Patient Care and Clinical Practice: Omadacycline is active against staphylococci, including methicillin-resistant strains, and streptococci, including tetracycline-resistant strains, as well as atypical bacteria. Omadacycline provides clinicians with an additional parenteral and oral option for the treatment of adults with ABSSSI and CABP., Conclusion: Omadacycline is an alternative treatment option for ABSSSI and CABP.

Antibiotic use is a primary driver of antibiotic resistance. However, antibiotic use can be distributed in different ways in a population, and the association between the distribution of use and antibiotic resistance has not been explored. Here, we tested the hypothesis that repeated use of antibiotics has a stronger association with population-wide antibiotic resistance than broadly-distributed, low-intensity use. First, we characterized the distribution of outpatient antibiotic use across US states, finding that antibiotic use is uneven and that repeated use of antibiotics makes up a minority of antibiotic use. Second, we compared antibiotic use with resistance for 72 pathogen-antibiotic combinations across states. Finally, having partitioned total use into extensive and intensive margins, we found that intense use had a weaker association with resistance than extensive use. If the use-resistance relationship is causal, these results suggest that reducing total use and selection intensity will require reducing broadly distributed, low-intensity use., Competing Interests: SO, MB, DM, JB, SH, YG No competing interests declared, ML Reviewing editor, eLife, (© 2018, Olesen et al.)

Interest in bronchiectasis has increased over the past two decades, as shown by the establishment of disease-specific registries in several countries, the publication of management guidelines and a growing number of clinical trials to address evidence gaps for treatment decisions. This review considers the evidence for defining and treating pulmonary exacerbations, the approaches for eradication of newly identified airway pathogens and the methods to prevent exacerbations through long-term treatments from a pragmatic practice-based perspective. Areas for future studies are also explored. Watch the video abstract., (© 2018 Asian Pacific Society of Respirology.)

We sought to determine if clinical data validate the dogma that bactericidal antibiotics are more clinically effective than bacteriostatic agents. We performed a systematic literature review of published, randomized, controlled trials (RCTs) that compared a bacteriostatic agent to a bactericidal agent in the treatment of clinical, bacterial infections. Of 56 identified trials published since 1985, 49 found no significant difference in efficacy between bacteriostatic and bactericidal agents. In 6 trials it was found that the bacteriostatic agent was superior to the bactericidal agent in efficacy. Only 1 trial found that the bactericidal agent was superior; in that case, the inferiority of the static agent was explainable by underdosing of the drug based on pharmacokinetic-pharmacodynamic analysis. Thus, virtually all available data from high-quality, RCTs demonstrate no intrinsic superiority of bactericidal compared to bacteriostatic agents. Other drug characteristics such as optimal dosing, pharmacokinetics, and tissue penetration may be more important efficacy drivers.

Background: Pediatric stewardship programs have been successful at reducing unnecessary antibiotic use. Data from nonfreestanding children's hospitals are currently limited. This study is an analysis of antibiotic use after implementation of an antimicrobial stewardship program at a community nonfreestanding children's hospital., Methods: In April 2013, an antimicrobial stewardship program that consisted of physician-group engagement and pharmacist prospective auditing and feedback was initiated. We compared antibiotic use in the preintervention period (April 2012 to March 2013) with that in the postintervention period (April 2013 to March 2015) in all units except the neonatal intensive care unit and the emergency department. In addition, drug-acquisition costs, antibiotic-specific use, death, length of stay, and case-mix index were examined., Results: Antibiotic use decreased by 16.8% (95% confidence interval, 18.0% to -9.2%; P < .001) in the postintervention period. Vancomycin use decreased by 38% (P = .001), whereas antipseudomonal β-lactam use was unaltered. Drug-acquisition cost savings were estimated to be $67 000/year over the 2-year postintervention period. Lengths of stay and mortality rates were unchanged in the postintervention period after adjusting for case-mix index., Conclusions: Implementation of a simple stewardship initiative with limited resources at a community nonfreestanding children's hospital effectively reduced antibiotic use without an overt negative impact on overall clinical outcomes. The results of this study suggest that nonfreestanding children's hospitals can achieve substantial reductions in antibiotic use despite limited resources., (© The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The introduction of antibiotics into clinical practice revolutionized the treatment and management of infectious diseases. Before the introduction of antibiotics, these diseases were the leading cause of morbidity and mortality in human populations. This review presents a brief history of discovery of the main antimicrobial classes (arsphenamines, β-lactams, sulphonamides, polypeptides, aminoglycosides, tetracyclines, amphenicols, lipopeptides, macrolides, oxazolidinones, glycopeptides, streptogramins, ansamycins, quinolones, and lincosamides) that have changed the landscape of contemporary medicine. Given within a historical timeline context, the review discusses how the introduction of certain antimicrobial classes affected the morbidity and mortality rates due to bacterial infectious diseases in human populations. Problems of resistance to antibiotics of different classes are also extensively discussed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In this cross-sectional study, data were collected from responses to a questionnaire on dispensing frequencies of antimicrobials used by dairy practitioners in Ontario in dairy cattle in 2001. Data were validated through clinical case scenarios. Respondents reported using antimicrobials across all categories of importance to human medicine (medically important, Categories I to III) with a diversity of treatment combinations and routes of administration. Respondents anticipated that a request for direct veterinary supervision by producers was dependent on case severity, highlighting the importance of on-farm diagnostic and treatment protocols. Knowledge of the antimicrobials used in lactating cow therapy, and their frequency and reasons for use, will provide baseline information and contribute to antimicrobial stewardship in this food-animal production sector.

Background and Objectives: Appendicitis guidelines recommend either narrower- or extended-spectrum antibiotics for treatment of complicated appendicitis. The goal of this study was to compare the effectiveness of extended-spectrum versus narrower-spectrum antibiotics for children with appendicitis., Methods: We performed a retrospective cohort study of children aged 3 to 18 years discharged between 2011 and 2013 from 23 freestanding children's hospitals with an appendicitis diagnosis and appendectomy performed. Subjects were classified as having complicated appendicitis if they had a postoperative length of stay ≥3 days, a central venous catheter placed, major or severe illness classification, or ICU admission. The exposure of interest was receipt of systemic extended-spectrum antibiotics (piperacillin ± tazobactam, ticarcillin ± clavulanate, ceftazidime, cefepime, or a carbapenem) on the day of appendectomy or the day after. The primary outcome was 30-day readmission for wound infection or repeat abdominal surgery. Multivariable logistic regression, propensity score weighting, and subgroup analyses were used to control for confounding by indication., Results: Of 24 984 patients, 17 654 (70.7%) had uncomplicated appendicitis and 7330 (29.3%) had complicated appendicitis. Overall, 664 (2.7%) patients experienced the primary outcome, 1.1% among uncomplicated cases and 6.4% among complicated cases (P < .001). Extended-spectrum antibiotic exposure was significantly associated with the primary outcome in complicated (adjusted odds ratio, 1.43 [95% confidence interval, 1.06 to 1.93]), but not uncomplicated, (adjusted odds ratio, 1.32 [95% confidence interval, 0.88 to 1.98]) appendicitis. These odds ratios remained consistent across additional analyses., Conclusions: Extended-spectrum antibiotics seem to offer no advantage over narrower-spectrum agents for children with surgically managed acute uncomplicated or complicated appendicitis., (Copyright © 2016 by the American Academy of Pediatrics.)

After some years of stagnation there have been several new successful developments in the field of antibacterial agents. Most of these new developments have been in conventional antibacterial classes. New drugs among the beta-lactam agents are methicillin-resistant Staphylococcus aureus (MRSA) active cephalosporins (ceftaroline and ceftobiprole) and new combinations of beta-lactam with beta-lactamase inhibitors (ceftolozane/tazobactam, ceftazidime/avibactam, imipenem/relebactam and meropenem/RPX7009). New developments can also be observed among oxazolidinones (tedizolid, radezolid, cadazolid and MRX-I), macrolides/ketolides (modithromycin and solithromycin), aminoglycosides (plazomicin), quinolones (nemonoxacin, delafloxacin and avarofloxacin), tetracyclines (omadacycline and eravacycline) as well as among glycopeptides and lipopeptides (oritavancin, telavancin, dalbavancin and surotomycin). New agents in a very early developmental phase are FabI inhibitors, endolysines, peptidomimetics, lipid A inhibitors, methionyl-tRNA synthetase inhibitors and teixobactin.

Prevention of infections and strategies for the prudent use of antimicrobials in long-term care facilities have gained importance in view of the demographic changes, not only in Germany. To generate appropriate data and to identify relevant aspects of infection prevention in this field, the European Centre for Disease Prevention and Control (ECDC) launched the second point prevalence survey of healthcare-associated infections and antimicrobial use in European long-term care facilities in 2013 (HALT-2). Despite methodical adjustments in the collection of data on healthcare-associated infections, in this second survey healthcare workers in the participating facilities were intensively trained in methodology and data collection. Overall, 221 German facilities participated and collected data from 17,208 residents. Well-established structures of regional networks facilitated the recruitment of participants as well as the preparations for training and survey. The median prevalence of residents receiving at least one antimicrobial agent was 1.1% (95 %-CI 0,7-1,6)), which is remarkably low. However, the most frequently used antimicrobials in German facilities beside beta-lactams (penicillins 18.2%, other beta-lactams 17.2%) were quinolones (28.2%). Data collection of infections was performed based on signs and symptoms in detailed decision algorithms according to the recently updated McGeer surveillance criteria and yielded a median prevalence of 1.7% (95 %-CI 1,1-2,2). Symptomatic urinary tract infections (28.4%), skin and soft tissue infection (27.9%), and respiratory tract infections (24.7%) were identified both as the most common types of infections and the most common indications for the use of systemic antimicrobials. Clinical implications evolve mainly from the high use of quinolones. In terms of infection prevention measures, compliance of health care workers with a hand hygiene regimen revealed further potential for improvement.

Objectives: Antibiotics are commonly classified into bactericidal and bacteriostatic agents based on their antimicrobial action. We aimed to assess whether this distinction is clinically relevant., Methods: OVID MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL) and relevant references and conference proceedings using the Web of Science and Scopus databases were searched for randomized controlled trials comparing bactericidal with bacteriostatic antibiotics for treatment of severe infections. Main outcome measures were clinical cure rates and overall mortality. Abstracts of studies selected in the database search were screened by one reviewer; full-text screening and data extraction were performed by three independent reviewers., Results: Thirty-three studies were included. Approximately half of patients were treated with bacteriostatic monotherapy. Infections covered were pneumonia (n=13), skin and soft tissue infections (n=8), intra-abdominal infections (n=4) and others (n=8). Neither clinical cure rates [risk ratio (RR), 0.99; 95% CI, 0.97-1.01; P=0.11] nor mortality rates (RR, 0.91; 95% CI, 0.76-1.08; P=0.28) were different between patients treated with bactericidal drugs and those treated with bacteriostatic drugs. Subgroup analyses showed a benefit for clinical cure rates associated with linezolid and increased mortality associated with tigecycline. In meta-regression, clinical cure rates remained higher in patients treated with linezolid (P=0.01); tigecycline displayed a close to significant association with increased mortality (P=0.05) if compared with other bacteriostatic agents., Conclusions: The categorization of antibiotics into bacteriostatic and bactericidal is unlikely to be relevant in clinical practice if used for abdominal infections, skin and soft tissue infections and pneumonia. Because we were not able to include studies on meningitis, endocarditis or neutropenia, no conclusion regarding these diseases can be drawn., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Therapeutic efficacy and safety in infections due to multiresistant bacteria can be improved by the clinical development of new compounds and devising new derivatives of already useful antibiotics. Due to a striking global increase of multiresistant gram-negative and gram-positive organisms, new antibiotics are urgently needed. This paper provides a review of new pharmaceuticals which are already in clinical development, mainly in phase III trials., Conclusion: Each of these new trials increases the possibility of new antibiotics receiving approval.

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., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2014) and reference lists of retrieved papers., Selection Criteria: We included randomised controlled trials comparing different classes of prophylactic antibiotics given to women undergoing caesarean section. We excluded trials that compared drugs with placebo or drugs within a specific class; these are assessed in other Cochrane reviews., Data Collection and Analysis: Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction., Main Results: We included 35 studies of which 31 provided data on 7697 women. For the main comparison between cephalosporins versus penicillins, there were 30 studies of which 27 provided data on 7299 women. There was a lack of good quality data and important outcomes often included only small numbers of women.For the comparison of a single cephalosporin versus a single penicillin (Comparison 1 subgroup 1), we found no significant difference between these classes of antibiotics for our chosen most important seven outcomes namely: maternal sepsis - there were no women with sepsis in the two studies involving 346 women; maternal endometritis (risk ratio (RR) 1.11, 95% confidence interval (CI) 0.81 to 1.52, nine studies, 3130 women, random effects, moderate quality of the evidence); maternal wound infection (RR 0.83, 95% CI 0.38 to 1.81, nine studies, 1497 women, random effects, low quality of the evidence), maternal urinary tract infection (RR 1.48, 95% CI 0.89 to 2.48, seven studies, 1120 women, low quality of the evidence) and maternal composite adverse effects (RR 2.02, 95% CI 0.18 to 21.96, three studies, 1902 women, very low quality of the evidence). None of the included studies looked for infant sepsis nor infant oral thrush.This meant we could only conclude that the current evidence shows no overall difference between the different classes of antibiotics in terms of reducing maternal infections after caesarean sections. However, none of the studies reported on infections diagnosed after the initial postoperative hospital stay. We were unable to assess what impact, if any, the use of different classes of antibiotics might have on bacterial resistance., Authors' Conclusions: Based on the best currently available evidence, cephalosporins and penicillins have similar efficacy at caesarean section when considering immediate postoperative infections. We have no data for outcomes on the baby, nor on late infections (up to 30 days) in the mother. Clinicians need to consider bacterial resistance and women's individual circumstances.

The aim of the present study was to describe the prescription rate and patterns of antibacterial agents in the Norwegian dog population in relation to time and place during 2004-2008. Prescription data were collected from the Norwegian prescription database (NorPD), whereas an estimate of the dog population was obtained from the Norwegian Kennel Club (NKK). Maps of the geographical prescription rate patterns were generated in the software ArcGIS 9.2. This study indicates an increased usage of antibacterial agents in dogs in Norway during the study period in which antibacterial agents for systemic use and especially the combination amoxicillin and clavulanic acid accounted for the major part. Among antibacterial agents defined as critically important for human medicine, an increase was observed in the prescription rate of quinolones. The geographical prescription rate patterns were stable during the study period, which indicated that the identified increase in usage of antimicrobial agents occurred all over the country, but that there were regional differences in the prescribing behaviour. Prescription data from the NorPD of antibacterial agents to dogs can be used as a basis to perform a risk-based sampling approach to detect emerging antimicrobial resistance in the dog population., (© 2012 Blackwell Publishing Ltd.)

This study investigated oral and parenteral antimicrobial use in dogs and cats, and evaluated antimicrobial use in feline upper respiratory tract disease (FURTD), feline lower urinary tract disease (FLUTD), and canine infectious tracheobronchitis. Study journals (n = 1807) were submitted by 84 veterinarians. Sixty-five percent of the antimicrobials prescribed in dogs and 67% in cats were β-lactams. Most frequently prescribed in dogs were cephalexin (33%) and amoxicillin-clavulanic acid (16%), and in cats, amoxicillin-clavulanic acid (40%) and cefovecin (17%); 7% of the prescriptions in dogs and 12% in cats were for fluoroquinolones. Sixty-seven percent of the disease events associated with canine infectious tracheobronchitis, and 70% and 74% associated with FURTD and FLUTD, respectively, were treated with antimicrobials. These results suggest that cefovecin and fluoroquinolones may be over-used and antimicrobial use for the treatment of FURTD, FLUTD, and canine infectious tracheobronchitis could probably be reduced to lessen resistance selection pressure without compromising patient health.

This article reviews the most important aspects of antibiotic treatment failure in respiratory tract infection which may occur with empirical as well as under target antibiotic therapy. Potential risk factors leading or predisposing to treatment failure exist in hospital acquired infections which cover polymicrobial aetiology with high multidrug resistance bacteria, changed conditions of pharmacokinetic and pharmacodynamic (PK/PD) parameters of antibiotics, bioavailability, drug interactions and inactivation. Microbial determinants of treatment failure includes bacterial physiology in laboratory cultures and inside the host, inadequate drug choice, lack of knowledge of PK/PD parameters with insufficient antibiotic level in target tissue. Differences between microbial in vitro tests and clinical outcome can be caused by varied CFU concentration, growing phase, nutritional, pH and redox conditions. Many factors of treatment failure are focused on bacterial biofilm structure and phenomenon of small-colony variants (SCVs) which both display reduced susceptibility to antimicrobial agents protected by matrix feature, enhanced production of PIA and by slow multiplication of biofilm forming cells.

Administration of empiric antimicrobial therapy is standard practice in the management of neutropenic fever, but there remains considerable debate about the selection of an optimal regimen. In view of emerging evidence regarding efficacy and toxicity differences between empiric treatment regimens, and strong evidence of heterogeneity in clinical practice, the current guidelines were developed to provide Australian clinicians with comprehensive guidance for selecting an appropriate empiric strategy in the setting of neutropenic fever. Beta-lactam monotherapy is presented as the treatment of choice for all clinically stable patients while early treatment with combination antibiotic therapy is considered for patients at higher risk. Due consideration is given to the appropriate use of glycopeptides in this setting. Several clinical caveats, accounting for institution- and patient-specific risk factors, are provided to help guide the judicious use of the agents described. Detailed recommendations are also provided regarding time to first dose, timing of blood cultures, selection of a first-line antibiotic regimen, subsequent modification of antibiotic choice and cessation of therapy., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

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., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2010) and reference lists of retrieved papers., Selection Criteria: We included randomised controlled trials comparing different classes of prophylactic antibiotics given to women undergoing caesarean section. We excluded trials that compared drugs with placebo or drugs within a specific class; these are assessed in other Cochrane Reviews., Data Collection and Analysis: Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction., Main Results: We included 29 studies of which 25 provided data on 6367 women. There was a lack of good quality data and important outcomes often included only small numbers of women. This meant we could only conclude that the current evidence shows no overall difference between the different classes of antibiotics in terms of reducing maternal infections after caesarean sections. However, none of the studies looked at outcomes on the baby, nor did they report infections diagnosed after the initial postoperative hospital stay. We were unable to assess what impact, if any, the use of different classes of antibiotics might have on bacterial resistance., Authors' Conclusions: Based on the best currently available evidence, cephalosporins and penicillins have similar efficacy at caesarean section when considering immediate postoperative infections. We have no data for outcomes on the baby, nor on late infections (up to 30 days) in the mother. Clinicians need to consider bacterial resistance and women's individual circumstances.

Objective: To assess the prevalence of antibiotic misuse among boarding secondary school students in Dares Salaam., Methodology: This descriptive cross-sectional study was conducted over 3-month period amongst boarding secondary school students. A randomized sample of students was recruited from at least 3 secondary schools from each of the three municipalities of Dar es Salaam region. Questionnaire with both closed-and open-ended questions was used for data collection in which socio-demographic characteristics, knowledge of ATBs, sources of prescription, procurement of ATBs, infections for which ATBs were used, and antibiotic therapy compliance were assessed. The collected data were analyzed using SPSS/PC+ version 15.0 computer package., Results: A total of 424 randomly selected students with a mean age of 20 years were interviewed, of those 150 were females and 274 were males. Majority of the respondents (74%) have had heard of ATBs, however only 105 (25%) respondent described them correctly. Prevalence of antibiotic usage among the students was high (69%). Of 293 students who have had used ATBs, 73% of them had procured the drugs on prescription; 170 (58%) respondents used the ATBs for non-microbial infections/diseases, only 183 (62%) were compliant to antibiotic therapies (ABT), while 226 (77%) admitted to have had shared ATBs with friends/relatives whenever deemed necessary. Of those who had procured ATBs without prescriptions, 66% of them obtained the drugs from pharmacies., Conclusion: The study revealed inadequate knowledge on ATBs among the respondents and that pharmacies played a major role on easy availability of ATBs as over-the-counter (OTC) drugs attributing to high rate of irrational use of ATBs. We recommended that health care providers should succinctly explain to patients the importance of ABT compliance and adverse effects of non-compliance. Regulatory authorities should re-enforce the laws on sales of ATBs by prohibiting their availability as OTC drugs.

Erythromycins have been part of our armamentarium against selected bacterial infections since they were discovered in 1952 and approved by the Food and Drug Administration (FDA) in 1964. In 1991, two newer, long-acting erythromycin analogues, azythromycin (brand name: Zithromax) and clarithromycin (brand name: Biaxin) were approved by the FDA. They were joined a few years later by a third long-acting form, dirithromycin (brand name: Dynabac).

Despite the constantly increasing need for new antimicrobial agents, antibiotic drug discovery and development seem to have greatly decelerated in recent years. Presented with the significant problem of advancing antimicrobial resistance, the global scientific community has attempted to find alternative solutions; one of the most promising ones is the evaluation and use of old antibiotic compounds. Due to the low-level use of many of the old antibiotic compounds, these have remained active against a large number of currently prevalent bacterial isolates. Thus, clinicians are beginning to re-evaluate their use in various patient populations and infections, despite the fact that they were previously thought to be less effective and/or more toxic than newer agents. A number of old antibiotic compounds, such as polymyxins, fosfomycin, fusidic acid, cotrimoxazole, aminoglycosides and chloramphenicol, are re-emerging as valuable alternatives for the treatment of difficult-to-treat infections. The availability of novel genetic and molecular modification methods provides hope that the toxicity and efficacy drawbacks presented by some of these agents can be surpassed in the future.

Many infectious diseases are caused by facultative organisms that are able to survive in phagocytic cells. The intracellular location of these microorganisms protects them from the host defence systems and from some antibiotics with poor penetration into phagocytic cells. One strategy used to improve the penetration of antibiotics into phagocytic cells is the use of carrier systems that deliver these drugs directly to the target cell. Delivery systems such as liposomes, micro/nanoparticles, lipid systems, conjugates, and biological carriers such as erythrocyte ghosts may contribute to increasing the therapeutic efficacy of antibiotics and antifungal agents in the treatment of infections caused by intracellular microorganisms. The main objective of this review is to analyze recent advances and current perspectives in the use of antibiotic delivery systems in the treatment of intracellular infections such as mycobacterial infections, brucellosis, salmonellosis, listeriosis, fungal infections, visceral leishmaniasis, and HIV.

We carried out a one-day prevalence survey of hospital-acquired infections (HAIs) and antimicrobial use in February 2006 in a paediatric hospital in Arkhangelsk, north-western Russia. A total 472 patients aged less than 18 years old were included in the study, of which 395 (84%) had been inpatients in the hospital for at least 48 h on the study day. The overall prevalence of HAI amongst the latter group of patients was 17% [67/395; 95% confidence interval (CI): 13.8-21.2] with upper respiratory tract infections being most frequently diagnosed (45%), followed by lower respiratory tract infections (19%) and urinary tract infections (12%). The highest proportion of HAI was found in patients less than one year old and in those with hospital stays of longer than 10 days. Antimicrobial agents were given to 39% of all hospitalized patients (183/472; 95% CI: 34.5-43.2). Cephalosporins accounted for 39% (82/211) of all antimicrobial prescriptions, followed by the penicillins (22%; 46/211). This study established a baseline for surveillance of HAI and antimicrobial use within the hospital, and facilitated the adoption of targeted infection control measures.

Antibiotics were initially viewed as "wonder drugs" primarily because they were introduced at a time when only surgical drainage or spontaneous cures were available to treat serious bacterial infections. During the five or six decades since their introduction, several classes of these drugs became available including sulfonamides and trimethoprim, penicillins, cephalosporins, chloramphenicol, tetracyclines, colimycins, macrolides, lincosamides, streptogramins, rifamycins, glycopeptides, aminoglycosides, fluoroquinolones, oxazolidinones, glycylglycines, lipoglycopeptides, and variations on these themes. Unfortunately, through a variety of mechanisms and perhaps as a result of their profligate use, many bacterial groups are exhibiting resistance to these antibiotics. At present, most bacterial infections can still be treated with available antibiotics used alone or in combination, but increasing numbers of clinical failures with the current armamentarium can be expected. Optimizing drug dosing and duration might help minimize the emergence of resistance in some situations. However, the future could look dim, as there are relatively few new agents on the horizon. A bold new look for antibacterial targets is needed. Surely our scientific abilities are up to this challenge. New approaches to antimicrobial chemotherapy are needed if we are to survive the increasing rates of antibiotic resistance predicted for the future.

Background: International guidelines recommend routine microbiological assessment of patients with febrile neutropenia, but do not recommend a change from broad-spectrum antibiotic therapy to pathogen-specific therapy when a clinically relevant organism has been isolated. The aim of the study was to determine the aetiology of febrile neutropenia in adult haematology patients at Auckland City Hospital, to document the changes in treatment made following isolation of a clinically relevant organism and to assess adverse outcomes in any patient who received pathogen-specific therapy after a positive culture result., Methods: The results of all microbiological tests together with antibiotic therapy were recorded from consecutive patients with fever and a neutrophil count <0.5 x 10(9)/L over 1 year beginning in May 2003., Results: One thousand one hundred and ninety-six specimens were collected from 81 patients during 116 episodes of febrile neutropenia. A pathogen was isolated from blood cultures in 40 episodes: Gram-positive cocci accounted for 46% of isolates and Gram-negative bacilli for 35%. Isolation of a pathogen from blood cultures resulted in a change of treatment in 25 of 40 (62.5%, 95%CI 46-77%) episodes. In 12 of these episodes, antibiotic therapy was optimized to a single pathogen-specific agent. No adverse events or subsequent changes in antibiotic therapy occurred in any of these 12 patients. Isolation of a pathogen from specimens other than blood seldom led to a change in therapy., Conclusion: Isolation of a pathogen from blood cultures often allows antibiotic therapy to be simplified to a pathogen-specific regimen. Further study of this approach is warranted.

The aim of this study was to determine if there were differences in the antibiotic consumption among the pediatric population of the eleven Primary Health Care centers in the Community of Castilla Leon during the years 2001-2005 and to analyze the possible causes. Data of non-hospital antibiotic consumption in the pediatric population provided the amount of antibiotics billed in the Health Service of the area of Castilla and Leon (central region of Spain). The data was analyzed according to the Anatomic Therapeutic Chemical Classification System (ATC) and expressed as defined daily doses per 1000 inhabitants per day (DID). There were statistically significant differences in the use of antibiotics, varying 8.3 DID between the area with the highest rate (24.86 DID in Leon) and the area with the lowest rate (16.56 DID in Soria). The temporal fluctuations were great and varied especially in Segovia. The pattern of prescribing also varied. The use of penicillin in combination with beta-lacatamase inhibitors varied by a factor of almost three times between Burgos and Segovia. Segovia showed the best management in antibiotic prescriptions with data showing low consumption based on prescribing recommendations. Data from Soria showed low consumption but patterns of misuse in regard to protocols and prescribing. There was wide quantitative and qualitative variability of antibiotic use among the primary health care centers in the region of Castilla and Leon. More detailed studies by age groups, welfare pressure and indication are needed to better understand the determinants of antibiotic use in children.

Background and Objective: Bacterial rhinosinusitis is one of the most frequent indications for an antibiotic therapy. The objective of this study was the analysis of the current pathogen spectrum and its antimicrobial susceptibility., Material and Methods: Between 1999 and 2004, 188 specimens obtained from 170 patients with acute, purulent rhinosinusitis were analysed., Results: A total of 217 pathogens were isolated. The most common isolates were Streptococcus pneumoniae (33%), Haemophilus influenzae (27%), Staphylococcus aureus (13%), Moraxella catarrhalis (11%) and streptococci (7%). S. pneumoniae, H. influenzae and M. catarrhalis were the predominant pathogens in children. S. pneumoniae, S. aureus and streptococci, however, dominated in specimens from adults., Conclusion: Based on these results, adults should be treated with an aminopenicillin with beta-lactamase inhibitor or a cephalosporin of the second generation. For children , however, the first line antibiotic is an aminopenicillin.

In Part 1 of this three-part series, an overview of how antimicrobials, the "silver bullets" of modern medicine, are designed to target specific agents of infection was given. The worldwide concern regarding antimicrobial resistance and the need for a more judicious approach to using antimicrobials was addressed. In this section, the focus is on those specific antimicrobial agents used to fight bacterial infections. Discussion addresses bacterial cell wall inhibitors (penicillins and cephalosporins), protein synthesis inhibitors (macrolides, tetracyclines, and aminoglycosides), and nucleic acid inhibitors (sulfonamides and quinolones). Examples of agents in each class are identified, with a look at the specific use, action, and potential for adverse effects. A general overview of patient teaching for antibacterial use is included.