Second-line Antimicrobials Research Articles

Preparation and antibacterial activity of coronarin E derivatives

Coronarin E is a main diterpene ever isolated from Hedychium yunnanense. With the aim to enlarge its potential application, four butenolide derivatives (compounds 4a, 4b, 5a and 5b) were obtained from coronarin E via synthetic method, and their antibacterial effects were also evaluated. It is noteworthy that compounds 5a and 5b exhibited stronger antibacterial activities against most of the tested bacterial strains than ampicillin and kanamycin, two first- and second-line antimicrobials in clinical. For example, minimum inhibitory concentration (MIC) of 5a, 5b, ampicillin and kanamycin against Acinetobacter baumanii were 2, 1, 8 and 4 μg/mL, respectively, and MIC of the four compounds mentioned above against Klebsiella pneumonia were 1, 0.5, 16 and 4 μg/mL, respectively. The current studies not only enrich the structural diversity of diterpenes derived from Hedychium genus, but also provide potent candidates for the development of antibacterial medicines.

Antimicrobial usage surveys using electronic medical records in cattle practice in Gifu Prefecture.

As the majority of antimicrobial treatments for cattle in Japan are prescribed by veterinarians, medical record information can be useful in clarifying the amount and purpose of antimicrobial use. In this study, we examined their amount and purpose in cattle practices in Gifu Prefecture. In cattle, approximately 85% of the antimicrobials are used for the treatment of gastrointestinal (50.4%) and respiratory diseases (34.4%). The main antimicrobials were sulfonamides (27.1 kg, 49.2%), followed by amphenicols (11.9 kg, 21.7%). As for second-line antimicrobials for veterinary treatment, fluoroquinolones, a third-generation cephalosporins, and 15 membered-ring macrolides, accounted for 5.6%, 0.1%, and 0.9% of all antimicrobials, respectively. Thus, medical record information may represent the actual situation of not only antimicrobial use, but also the significance of the disease in local regions.

Clinical predictors of bacteraemia in neonates with suspected early-onset sepsis in Malawi: a prospective cohort study

ObjectivesWe studied neonates with suspected early-onset sepsis (EOS, sepsis developing in the first 72 hours after delivery) in Malawi to (1) describe clinical characteristics and microbiological findings, (2) identify which...

Antimicrobial Resistance of Listeria monocytogenes from Animal Foods to First- and Second-Line Drugs in the Treatment of Listeriosis from 2008 to 2021: A Systematic Review and Meta-Analysis.

First-line drugs for the treatment of listeriosis are the same around the world, but particular conditions might reduce their efficacy, including antimicrobial resistance. Therefore, this study aimed to verify, based on a systematic review and meta-analysis, whether the prevalence of antimicrobial resistance in Listeria monocytogenes from animal foods is higher for first- or second-line antimicrobials. From the total of 302 identified studies, 16 met all the eligibility criteria from 2008 to 2021 and were included in this meta-analysis. They comprised a dataset of 1152 L. monocytogenes isolates, obtained from different animal food products, food processing environment, and live animals. The included studies were developed in South America (n = 5), Europe (n = 4), Asia (n = 3), Africa (n = 2), and North America (n = 2), testing a total of 35 different antimicrobials, 11 of them classified as first-line drugs. Complete lack of antimicrobial resistance across the studies (all L. monocytogenes isolates tested as susceptible) was only observed for linezolid, while widespread antimicrobial resistance (all L. monocytogenes isolates tested resistant) was described for amoxicillin, benzylpenicillin, cefoxitin, fusidic acid, imipenem, sulfamethoxazole, and vancomycin. Overall, the meta-analysis results indicated no evidence that antimicrobial resistance in L. monocytogenes isolated from animal-based food is higher for first-line antimicrobials compared to second-line compounds (p=0.37). A greater volume of publication, together with better characterization of the isolates, is still needed for a more precise estimate of the real prevalence of antimicrobial resistance in L. monocytogenes.

The Effect of Tuberculosis Antimicrobials on the Immunometabolic Profiles of Primary Human Macrophages Stimulated with Mycobacterium tuberculosis.

Tuberculosis (TB) remains a global health challenge. Patients with drug-sensitive and drug-resistant TB undergo long, arduous, and complex treatment regimens, often involving multiple antimicrobials. While these drugs were initially implemented based on their bactericidal effects, some studies show that TB antimicrobials can also directly affect cells of the immune system, altering their immune function. As use of these antimicrobials has been the mainstay of TB therapy for over fifty years now, it is more important than ever to understand how these antimicrobials affect key pathways of the immune system. One such central pathway, which underpins the immune response to a variety of infections, is immunometabolism, namely glycolysis and oxidative phosphorylation (OXPHOS). We hypothesise that in addition to their direct bactericidal effect on Mycobacterium tuberculosis (Mtb), current TB antimicrobials can modulate immunometabolic profiles and alter mitochondrial function in primary human macrophages. Human monocyte-derived macrophages (hMDMs) were differentiated from PBMCs isolated from healthy blood donors, and treated with four first-line and six second-line TB antimicrobials three hours post stimulation with either iH37Rv-Mtb or lipopolysaccharide (LPS). 24 h post stimulation, baseline metabolism and mitochondrial function were determined using the Seahorse Extracellular Flux Analyser. The effect of these antimicrobials on cytokine and chemokine production was also assayed using Meso Scale Discovery Multi-Array technology. We show that some of the TB antimicrobials tested can significantly alter OXPHOS and glycolysis in uninfected, iH37Rv-Mtb, and LPS-stimulated hMDMs. We also demonstrate how these antimicrobial-induced immunometabolic effects are linked with alterations in mitochondrial function. Our results show that TB antimicrobials, specifically clofazimine, can modify host immunometabolism and mitochondrial function. Moreover, clofazimine significantly increased the production of IL-6 in human macrophages that were stimulated with iH37Rv-Mtb. This provides further insight into the use of some of these TB antimicrobials as potential host-directed therapies in patients with early and active disease, which could help to inform TB treatment strategies in the future.

Extraintestinal Pathogenic Escherichia coli ST405 Isolate Coharboring blaNDM-5 and blaCTXM-15: A New Threat in Mozambique.

The development of carbapenem resistance in extraintestinal pathogenic Escherichia coli (ExPEC) has significant clinical implications, particularly in countries where second-line antimicrobials are not readily available, rendering treatments ineffective, and ExPEC infections untreatable. Thus, early detection of high-risk ExPEC lineages and raising awareness of the specific mechanisms underlying carbapenem resistance are mandatory for the selection of appropriate treatment options and the prevention of E. coli spread. This study aims to investigate the phenotypic and genotypic features of the first NDM-5 carbapenemase-producing ExPEC strain isolated from the blood of a patient admitted to the Maputo Central Hospital (MCH), in Mozambique. E. coli SSM100 isolate was identified by MALDI-TOF, it displayed high-level resistance to third generation cephalosporins, carbapenems, fluoroquinolones, and aminoglycosides, performing antimicrobial susceptibilities testing by VITEK 2 system. E. coli SSM100 isolate was classified through whole-genome sequencing as ST405-D-O102: H6, a globally distributed lineage associated with antimicrobial resistance, carrying the blaNDM-5 gene located on an F1:A1:B49 plasmid, coharboring blaCTX-M-15, blaTEM-1, aadA2, sul1, and dfrA12 genes. In addition, mutations in gyrA (S83L and D87N), parC (S80I and E84V), and parE (I529L) conferring fluoroquinolone resistance were also found. Moreover, SSM100 isolate carried 88 virulence genes, of which 28 are reported to be associated with UPEC. The emergence of NDM-5 carbapenemase in a pandemic ST405-D-O102:H6 clone in Mozambique is of great concern. Locations of extended-spectrum β-lactamase determinants and NDM-5 carbapenemase gene on IncF-plasmid can increase their spread reinforcing the need for antimicrobial surveillance and the urgent introduction of carbapenemase detection tests in diagnostic laboratories of the country.

The Iron Chelator Desferrioxamine Increases the Efficacy of Bedaquiline in Primary Human Macrophages Infected with BCG.

For over 50 years, patients with drug-sensitive and drug-resistant tuberculosis have undergone long, arduous, and complex treatment processes with several antimicrobials. With the prevalence of drug-resistant strains on the rise and new therapies for tuberculosis urgently required, we assessed whether manipulating iron levels in macrophages infected with mycobacteria offered some insight into improving current antimicrobials that are used to treat drug-resistant tuberculosis. We investigated if the iron chelator, desferrioxamine, can support the function of human macrophages treated with an array of second-line antimicrobials, including moxifloxacin, bedaquiline, amikacin, clofazimine, linezolid and cycloserine. Primary human monocyte-derived macrophages were infected with Bacillus Calmette-Guérin (BCG), which is pyrazinamide-resistant, and concomitantly treated for 5 days with desferrioxamine in combination with each one of the second-line tuberculosis antimicrobials. Our data indicate that desferrioxamine used as an adjunctive treatment to bedaquiline significantly reduced the bacterial load in human macrophages infected with BCG. Our findings also reveal a link between enhanced bactericidal activity and increases in specific cytokines, as the addition of desferrioxamine increased levels of IFN-γ, IL-6, and IL-1β in BCG-infected human monocyte-derived macrophages (hMDMs) treated with bedaquiline. These results provide insight, and an in vitro proof-of-concept, that iron chelators may prove an effective adjunctive therapy in combination with current tuberculosis antimicrobials.

High burden of infections caused by ESBL-producing MDR Escherichia coli in paediatric patients, Yangon, Myanmar.

BackgroundThere is mounting evidence of a high burden of antimicrobial-resistant infections in children in low- and middle-income countries (LMICs).ObjectivesTo detect the frequency of ESBL-producing Escherichia coli in clinical specimens from paediatric patients attending Yangon Children’s Hospital in Myanmar.MethodsAll children attending Yangon Children’s Hospital who had clinical specimens submitted to the hospital diagnostic microbiology laboratory from June 2019 to December 2019 were included in the study. Specimens were processed routinely using standard methods with BD Phoenix used for pathogen identification and susceptibility testing. Presence of ESBLs was determined using the cephalosporin/clavulanate combination disc method with confirmation by PCR.ResultsFrom 3462 specimens submitted to the Microbiology Laboratory, a total of 123 E. coli were isolated. Among them, 100 isolates were phenotypically ESBL producers, 94 (76.4%) of which were confirmed by PCR [82/94 (87%) CTX-M, 72/94 (77%) TEM, 1/94 (1%) SHV]. Most of the ESBL-producing E. coli were isolated from urine samples (52.1%, 49/94) and the majority were from the surgical unit (61.7%, 58/94). Only 34/94 (36%) isolates were susceptible to meropenem.ConclusionsThis study confirms a high proportion of infections caused by ESBL-producing and MDR E. coli in children hospitalized in Yangon, where access to effective second-line antimicrobials is limited.

Molecular characterization of methicillin-resistant Staphylococcus aureus clinical strains from the endotracheal tubes of patients with nosocomial pneumonia

BackgroundAmong all cases of nosocomial pneumonia, Staphylococcus aureus is the second most prevalent pathogen (17.8%). In Europe, 29.9% of the isolates are oxacillin-resistant. The changing epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial infections and the decreasing susceptibility to first-line antibiotics leave clinicians with few therapeutic options. The objective of our study was to determine the antimicrobial susceptibility, the associated molecular mechanisms of resistance and the epidemiological relatedness of MRSA strains isolated from the endotracheal tubes (ETT) of intubated critically ill patients in the intensive care unit (ICU) with nosocomial pneumonia caused by Staphylococcus aureus.MethodsThe antimicrobial susceptibility to vancomycin, linezolid, ciprofloxacin, clindamycin, erythromycin, chloramphenicol, fusidic acid, gentamicin, quinupristin-dalfopristin, rifampicin, sulfamethoxazole/trimethoprim, and tetracycline were measured. Resistance mechanisms were then analyzed by polymerase chain reaction and sequencing. Molecular epidemiology was carried out by multi-locus sequence typing.ResultsS. aureus isolates were resistant to ciprofloxacin, erythromycin, gentamicin, tetracycline, clindamycin, and fusidic acid. The most frequent mutations in quinolone-resistant S. aureus strains were S84L in the gyrA gene, V511A in the gyrB gene, S144P in the grlA gene, and K401R/E in the grlB gene. Strains resistant to erythromycin carried the ermC, ermA, and msrA genes; the same ermC and ermA genes were detected in strains resistant to clindamycin. The aac(6′)-aph(2″) gene was related to gentamicin resistance, while resistance to tetracycline was related to tetK (efflux pump). The fusB gene was detected in the strain resistant to fusidic acid. The most frequent sequence types were ST22, ST8, and ST217, which were distributed in four clonal complexes (CC5, CC22, CC45, and CC59).ConclusionsHigh levels of resistance to second-line antimicrobials threatens the treatment of nosocomial respiratory infections due to methicillin-resistant S. aureus with decreased susceptibility to linezolid and vancomycin. The wide genotypic diversity found reinforces the central role of ICU infection control in preventing nosocomial transmission.

Unexpected relationships between frequency of antimicrobial resistance, disease phenotype and emm type in group A Streptococcus.

Despite universal susceptibility to β-lactams, resistance to second-line antimicrobials (e.g. erythromycin) is increasingly common among group A Streptococcus (GAS). To better understand the frequency of regional GAS antimicrobial resistance, we screened a previously described GAS strain collection from Houston, TX, USA, for resistance to commonly used antimicrobials. A total of 100/929 (10.8 %) showed resistance to at least one antimicrobial. Tetracycline resistance was identified in 52 (5.6 %) GAS strains. The cumulative frequency of erythromycin and clindamycin resistance [macrolide (M) and macrolide-lincosamide-streptogramin (MLS) phenotypes] was greatest among invasive GAS strains (9.9 %) compared to that of strains derived from any other infection type (5.9 %, P=0.045). We identified emm types 11, 75, 77 and 92 as the only emm types with high (e.g. >50 %) within-emm type resistance and contributing to the majority (24/26; 92 %) of erythromycin/clindamycin resistance in invasive GAS. High-frequency resistance emm types were also significantly overrepresented in invasive GAS strains as indicated by invasive index. We performed whole-genome sequencing to define genetic elements associated with resistance among emm types 11, 75, 77 and 92. Diverse mobile elements contributed to GAS resistance including transposons, integrative conjugative elements, prophage and a plasmid. Phylogenetic analysis suggests recent clonal emergence of emm92 GAS strains. Our findings indicate that less frequently encountered GAS emm types disproportionately contribute to resistance phenotypes, are defined by diverse mobile genetic elements and may favour invasive disease.

Improving Antimicrobial Prescribing: A Multinomial Model Identifying Factors Associated With First- and Second-Line Prescribing

Background/objectivesBroad-spectrum, second-line antimicrobials may be prescribed when initial first-line options prove ineffective. This study compares prescribing practices and identifies potential influencing factors for first- and second-line antimicrobials in long-term care facilities. DesignPoint prevalence survey of health care–associated infections and antimicrobial use in long-term care facilities (HALT), expanded by additional data collection. SettingLong-term care facilities in Ireland. ParticipantsOf long-term care facilities that participated in the HALT study 2016, additional data provided by 77 facilities with a record of 3677 residents. MeasurementOn the survey date, an institutional questionnaire was completed by each participating long-term care facility, and resident questionnaires were completed only for those residents who met a health care–associated infection surveillance definition and/or were prescribed a systemic antimicrobial. All participating long-term care facilities were contacted at a later time point to provide limited anonymized data (age, sex, urinary catheterization, and disorientation) on all current residents. These additional data were matched to the original data set, facilitating multilevel multinominal logistic regression (first-line/second-line/no antimicrobial). ResultsOf 3677 residents in 77 long-term care facilities, 381 (10%) were prescribed systemic antimicrobials on the survey day. Of those, 46% were categorized as second-line choices, with substantial interfacility variation observed with regard to prescription of first- versus second-line antimicrobials. The odds of a second-line antimicrobial prescription for a resident doubled when comparing the highest with the lowest prescribing long-term care facilities (median odds ratio = 2.0, credibility interval = 1.5-2.9). Male residents were less often prescribed first-line antimicrobials [odds ratio (OR) = 0.6, 95% confidence interval (CI) = 0.4-0.9, P = .02]. Long-term care facilities that reported the provision of education on antimicrobial prescribing use significantly less second-line antimicrobials (OR = 0.2, 95% CI = 0.1-0.7, P = .02). Females and residents with a urinary catheter were more likely to receive first-line antimicrobials. Conclusion/ImplicationsThe use of second-line antimicrobials is common practice in long-term care facilities, but education and training on appropriate antimicrobial use has the potential to reduce second-line antimicrobial prescribing, improve patients' outcomes, and reduce antimicrobial resistance.

270. Prevalence and Impact of β-Lactam Allergies at a Canadian Pediatric Center

BackgroundRational and appropriate use of antibiotics is a global priority since inappropriate or unnecessary use is associated with antibiotic resistance and patient morbidity. In adult patients, the presence of a β-lactam allergy label (BLA) often leads to the use of broader spectrum agents with more toxicity. Infections account for a majority of pediatric hospital admissions, and β-lactam antibiotics are often considered first-line therapy. There is limited evidence on the impact of BLA on prescribing practices in pediatrics. The primary objective of this study was to determine the proportion of children with a reported BLA who received second-line antimicrobials (as determined by hospital empiric antibiotic guidelines). The secondary objective was to identify patient characteristics associated with receiving second-line antibiotics.MethodsA 1-year retrospective cohort study was undertaken at the Hospital for Sick Children. We reviewed the characteristics and management of patients with a reported BLA who received antibiotics from January to December 2016.ResultsOf the 16,224 admissions in 2016, 206 patients with a reported BLA received antibiotics. Among these patients, the median age was 7.9 years (IQR 4.0, 12.8) and the majority of patients had at least one medical condition (n = 120, 59.3%), including 27 children with complex medical or genetic conditions (13.1%). Penicillin (n = 86, 41.8%) and amoxicillin (n = 70, 33.9%) were the most commonly reported allergens. Nonsevere rashes were the most commonly reported allergic reactions (n = 158, 73.1%). Ninety-four patients (46%; 95% CI (0.39,0.52) received second-line therapy. After adjusting for age and sex, the odds of receiving a second-line antibiotic were increased in patients with any underlying medical condition (OR = 2.45, 95% CI 1.32–4.56), had a reported allergic reaction that was deemed high-risk (i.e., anaphylaxis, respiratory or systemic symptoms, severe rashes) (OR = 2.61, 95% CI 1.11–6.11) or who received antibiotics for surgical prophylaxis (OR = 3.30, 95% CI 1.44–7.54).ConclusionAlmost half of pediatric patients with a reported BLA received a second-line antibiotic when compared with hospital empiric antibiotic guidelines. There is a need for a systematic approach to evaluating reported BLA in order to promote judicious prescribing habits.Disclosures All authors: No reported disclosures.

Clinical Characteristics of Anorectal Mycoplasma genitalium Infection and Microbial Cure in Men Who Have Sex With Men.

We report clinical characteristics of proctitis caused solely by Mycoplasma genitalium (MG) compared with chlamydia and gonococcus. We determined the proportions cured with first-line (azithromycin) and second-line antimicrobials (moxifloxacin, pristinamycin). A total of 166 patients attending Melbourne Sexual Health Centre from 2012 to 2016 with symptoms of proctitis were tested for MG, Chlamydia trachomatis, and Neisseria gonorrhoeae. Demographic characteristics, sexual behaviors, clinical symptoms, and signs were recorded. Multinomial multivariable logistic regression was used to test for significant differences in symptoms and signs for the pathogens detected. Seventeen percent of men had MG (95% confidence interval, 12-24), 21% had chlamydia (15-27), and 40% had gonococcal monoinfection (32-48), whereas 22% had MG coinfection (16-29). Relative to men with MG monoinfection, those with chlamydial monoinfection reported more anal pain (adjusted prevalence odds ratio (aPOR), 4.68 [1.41-14.19]), whereas men with gonococcal monoinfection reported more anal pain (aPOR, 6.75 [2.21-20.55]) and tenesmus (aPOR, 15.44 [1.62-146.90]), but less anal itch (aPOR, 0.32 [0.11-0.93]). The microbiological cure for MG using azithromycin was low at 35% (22-50), whereas moxifloxacin subsequently cured 92% (64-100) and pristinamycin cured 79% (54-94) of infections. M. genitalium was almost as common as chlamydia in men presenting to a sexual health center with symptoms of proctitis. Men with anorectal MG monoinfection were less likely to have symptoms and signs compared with those with chlamydia or gonococcus monoinfection. Cure for men with symptomatic anorectal MG by azithromycin was low. We suggest routine testing for MG in cases of proctitis, with test of cure after treatment being essential.

High rates of colonisation with ESBL (+) gram negative bacteria in newly admitted neonates in a neonatal care unit, Port au Prince, Haiti

Background Nosocomial invasive Gram negative bacterial (GNB) infections are common causes of mortality in neonatal care units (NCU). Gastrointestinal tracts of hospitalized infants can serve as a reservoir for these infections. We aimed to estimate the faecal colonisation proportion by GNB and ESBL (+) GNB of systematically sampled newly admitted neonates in an NCU in Haiti, to describe the antimicrobial resistance profiles (AMR) of isolated GNB and identify factors associated with colonisation. Materials/methods We included all neonates admitted to the NCU from May to August 2016 who were started on prophylactic antibiotics or treated for infection. Neonates had fecal swabs taken before treatment was initiated; these were tested for GNB, AMR profiles and ESBL status. We calculated adjusted prevalence ratios (aPR) using binomial regression. Results Of the 800 neonates admitted in NCU, 409 were treated with antimicrobials and 78 received second treatment. One hundred and twenty-five out of 279 (45%) screened neonates were colonised by GNB, 85% before the second treatment and 34% before the first treatment (aPR 2.5; 95% CI: 2.0–3.0). Twenty-three percent (52/224) of neonates were colonised by ESBL (+) GNB, 70% (32/46) before the second treatment, 8.8 (95% CI: 5.6–14) times higher than those before first treatment (7.9%; 20/254). Ninety-eight out of 175 (56%) of isolated GNB were Escherichia coli, Klebsiella oxytoca and Klebsiella pneumoniae. Fifty percent of the tested GNB were susceptible to first-line antimicrobials and 99% to second-line antimicrobials; 4% and 35% of isolates indicated intermediate resistance to amikacin and ceftazidime, respectively. Vaginal delivery (aPR 2.1; 95% CI: 1.4–3.2) and length of stay (aPR 1.82; 95% CI: 1.2–2.7) were associated with GNB colonisation among newly admitted neonates. Neonates sampled > 48 h after admission were 19 times more likely to be colonised by ESBL (+) GNB (aPR 19; 95% CI: 8.9–41) than those sampled Conclusions GNB colonisation was high and increased with length of stay. Second line antimicrobial treatment seems still adequate, but signs of intermediate resistance to ceftazidime were observed. We recommend to re-enforce: –surveillance for suspected pathogens of nosocomial infections using blood cultures for septic infants; –monitoring of antimicrobial treatment failure in infants receiving antibiotics.

Clinical and laboratory standards institute versus European committee for antimicrobial susceptibility testing guidelines for interpretation of carbapenem antimicrobial susceptibility results for Escherichia coli in urinary tract infection (UTI).

BACKGROUND:Carbapenems show excellent activity against resistant uropathogens, and they are the antibiotics of choice for urinary tract infections (UTIs). The choice of carbapenem prescription is strongly influenced by antimicrobial susceptibility testing (AST) report. With the publication of recent AST guidelines by the European Committee on AST (EUCAST), we were curious to evaluate the difference in results between Clinical and Laboratory Standards Institute (CLSI) and the EUCAST guidelines for the interpretation of carbapenems.METHODS:During a period of 1 year, midstream urine specimens received in the laboratory were cultured by conventional techniques and 2932 of them grew significant colony counts of Escherichia coli. Out of them, 501 E. coli isolates which were resistant to at least six first-line antibiotics were further subjected to second-line antimicrobials imipenem and meropenem, reported by E-tests (bioMerieux, France). The E-test results were interpreted by both CLSI 2016 and EUCAST 6.0 (2016) guidelines. Weighted kappa was used to determine absolute agreement, and McNemar's Chi-square test was used to test the difference in proportions of susceptibility between two methods, respectively.RESULTS:Taking CLSI guidelines as a gold standard, there was 100% sensitivity in a susceptible category by the EUCAST guidelines for both the carbapenems. Weighted kappa showed good and moderate agreement between them for imipenem and meropenem, respectively. However, McNemar Chi-square test in the nonsusceptible category between the two tests was 9.38% and 33.03% for imipenem and meropenem, respectively, and they were highly significant (P < 0.001).CONCLUSIONS:A laboratory can follow EUCAST guidelines as well and the guidelines are more useful in urinary concentrated antibiotics such as carbapenems. Further other antibiotics need to be evaluated by both these guidelines.

Intravenous Fosfomycin: An Assessment of Its Potential for Use in the Treatment of Systemic Infections in Canada.

Fosfomycin is a bactericidal agent that inhibits cell wall synthesis using a mechanism of action distinct from β-lactams or other antimicrobial agents. It is a broad-spectrum agent that is frequently active against antimicrobial-resistant bacterial pathogens including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Enterobacteriaceae, and some isolates of MDR Pseudomonas aeruginosa. Intravenous fosfomycin has been prescribed for a wide variety of infections in many countries for >40 years. It is most frequently used in combination with other antimicrobial agents (e.g., β-lactams, carbapenems, and aminoglycosides) and has an excellent safety profile, including in neonates and children, even with long-term administration (weeks). Fosfomycin achieves extensive tissue distribution including difficult to reach compartments such as aqueous humor, vitreous humor, abscess fluid, and CSF. Available data, to date, suggest no clinically relevant pharmacological interactions between fosfomycin and other agents, including drugs, stimulants, or food. Intravenous fosfomycin's role in therapy in Canada is likely as an agent used alone or in combination for complicated urinary tract infections in hospitalized patients as well as hospitalized patients with MDR infections who have not responded to first-, and potentially, second-line antimicrobials or in patients who cannot tolerate (due to adverse effects) first- and second-line antimicrobials.

Minimum inhibitory concentration distributions for first- and second-line antimicrobials against Mycobacterium tuberculosis.

We report the range of minimum inhibitory concentrations for six antimicrobial drugs in 228 clinical Mycobacterium tuberculosis (MTB) isolates from three distinct groups of patients (unselected patients, patients at high risk of drug-resistant TB and HIV-positive patients) in Lima, Peru. These data highlight the challenges of and discriminatory characteristics required for MTB drug susceptibility testing.

Pathogen and antimicrobial resistance profiles of culture-proven neonatal sepsis in Southwest China, 1990-2014.

Neonatal sepsis (NS) sustains high mortality and morbidity in China, but data on the epidemiology and antimicrobial resistance patterns of NS pathogens are limited. The clinical features, aetiology and antimicrobial resistance of culture-proven NS were analysed over a period of 25 years in the metropolitan city of Chongqing in Southwest China. The occurrence rates of neonatal early-onset sepsis (EOS) were found to gradually decrease while late-onset sepsis (LOS) was kept stable from 1990 to 2014. Although coagulase-negative staphylococcus (CoNS) sepsis accounted for most infections, the occurrence rates of CoNS sepsis gradually decreased, especially in EOS. Escherichia coli and Klebsiella were common Gram-negative bacteria. The occurrence rates of E. coli and Klebsiella remained stable in EOS; however, in LOS, those had increased mildly, especially from 2009 to 2014. Although a high-degree resistance to common first- and second-line antimicrobials was observed for the main causative pathogens of NS, the gentamicin-resistance rate declined gradually from the year 2003. Similarly, the ceftazidime-resistance rate of E. coli dropped gradually from the year 2007. The alarmingly high degree of antibiotic resistance calls for urgent evaluation and development of antibiotic policy and protocols for the treatment of NS. Clinicians should strictly control the antibiotics use, decrease invasive manipulations and shorten hospitalisation to prevent LOS.

The potential role of trimethoprim-sulfamethoxazole in the treatment of drug-resistant tuberculosis.

Tuberculosis (TB) remains a serious public health threat worsened by emerging drug resistance. Mycobacterium tuberculosis has become resistant not only to front-line drugs but also to second-line antimicrobials directed at drug-resistant TB. Renewed efforts are devoted for the development of new antibiotics active against TB. Also, repurposing of other antibiotics is being explored to shorten the time to develop new drugs against M. tuberculosis. As a result, trimethoprim-sulfamethoxazole (SXT) has emerged as a potential new option to treat drug-resistant TB. SXT has been found to be surprisingly active against drug-resistant M. tuberculosis, not only in vitro but also in vivo. The potential role of SXT for the treatment of multidrug resistant/extensively drug resistant TB might be explored in further clinical evaluations.

Canadian Multicenter Laboratory Study for Standardized Second-Line Antimicrobial Susceptibility Testing of Mycobacterium tuberculosis

The purpose of this study was to establish a standardized protocol for second-line antimicrobial susceptibility testing of Mycobacterium tuberculosis using the Bactec MGIT 960 system in Canadian laboratories. Four Canadian public health laboratories compared the susceptibility testing results of 9 second-line antimicrobials between the Bactec 460 and Bactec MGIT 960 systems. Based on the data generated, we have established that the Bactec MGIT 960 system provides results comparable to those obtained with the previous Bactec 460 method. The critical concentrations established for the testing of the antimicrobials used are as follows: amikacin, 1 μg/ml; capreomycin, 2.5 μg/ml; ethionamide, 5 μg/ml; kanamycin, 2.5 μg/ml; linezolid, 1 μg/ml; moxifloxacin, 0.25 μg/ml; ofloxacin, 2 μg/ml; p-aminosalicylic acid, 4 μg/ml; rifabutin, 0.5 μg/ml.