Search

Objective: To evaluate the serotype distribution and antibiotic resistance in pneumococcal infections in adults and to provide a perspective regarding serotype coverage of both current and future pneumococcal vaccines. Patients and methods: This passive surveillance study was conducted with the Streptococcus pneumoniae strains isolated from the specimens of patients with pneumonia (materials isolated from bronchoalveolar lavage), bacteraemia, meningitis, pleuritis and peritonitis between 2015 and 2018. Serogrouping and serotyping were performed by latex particle agglutination and by conventional Quellung reaction using commercial type-specific antisera, respectively. The strains were analysed for penicillin, cefotaxime, erythromycin and moxifloxacin susceptibilities by E-test. Results: In the whole study group (410 samples from adults aged ≥18 years), the most frequent serotypes were 3 (14.1%), 19 F (12%) and 1 (9.3%). The vaccine coverage for PCV13, PCV15, PCV20 and PPV23 was 63.9%, 66.6%, 74.1% and 75.9%, respectively, in all isolates. Penicillin non-susceptibility in invasive pneumococcal disease (IPD) was 70.8% and 57.1% in the patients aged

International audience; [No abstract available]

We characterized the antimicrobial resistance of 70 Escherichia coli isolates obtained from patients with a urinary tract infection (UTI) from 8 public hospitals in Peru. Resistance profiles were identified using the automated MicroScan® system. A standard polymerase chain reaction was used for the detection of the bla TEM, bla CTX-M, bla SHV and bla PER genes. The 65.7% (46/70) of the isolates presented a multidrug-resistant phenotype and 55.7% (39/70) were extended-spectrum beta-lactamases producers. High levels of resistance were detected for ampicillin (77,1%), ciprofloxacin (74,3%), trimethoprim/sulfamethoxazole (62,9%), cefepime (57,1%), and cefuroxime (57,1%). The bla TEM gene was the most frequent (31,4%), followed by bla CTX-M (18,6%) and bla SHV (2,9%) genes. These results show high resistance levels to antimicrobials of clinical use in E. coli isolates from hospital UTI patients in Peru.Se caracterizó la resistencia antimicrobiana de 70 aislados de Escherichia coli obtenidos de pacientes con infección del tracto urinario (ITU) provenientes de ocho hospitales públicos en el Perú. Los perfiles de resistencia fueron identificados mediante el uso del sistema automatizado MicroScan®. Se utilizó una reacción en cadena de la polimerasa convencional para la detección de los genes bla TEM, bla CTX-M, bla SHV y bla PER. El 65,7% (46/70) de los aislados presentó un fenotipo multidrogorresistente y el 55,7% (39/70) fue identificado como productores de betalactamasas de espectro extendido. Se detectaron altos niveles de resistencia para ampicilina (77,1%), ciprofloxacina (74,3%), trimetoprim/sulfametoxazol (62,9%), cefepime (57,1%) y cefuroxima (57,1%). El gen bla TEM fue el más frecuente con un 31,4%, seguido por bla CTX-M (18,6%) y bla SHV (2,9%). Los resultados evidencian altos niveles de resistencia a antimicrobianos de importancia clínica en aislados de E. coli de pacientes con ITU en el Perú.

Background The gut microbiota plays a central role in host physiology and in several pathological mechanisms in humans. Antibiotics compromise the composition and functions of the gut microbiota inducing long-lasting detrimental effects on the host. Recent studies suggest that the efficacy of different clinical therapies depends on the action of the gut microbiota. Here, we investigated how different antibiotic treatments affect the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in an experimental colitis model and in ex vivo experiments with human intestinal biopsies. Results Murine fecal donors were pre-treated with different antibiotics, i.e., vancomycin, streptomycin, and metronidazole before FMT administration to colitic animals. The analysis of the gut microbiome, fecal metabolome, and the immunophenotyping of colonic lamina propria immune cells revealed that antibiotic pre-treatment significantly influences the capability of the microbiota to control intestinal inflammation. Streptomycin and vancomycin-treated microbiota failed to control intestinal inflammation and were characterized by the blooming of pathobionts previously associated with IBD as well as with metabolites related to the presence of oxidative stress and metabolism of simple sugars. On the contrary, the metronidazole-treated microbiota retained its ability to control inflammation co-occurring with the enrichment of Lactobacillus and of innate immune responses involving iNKT cells. Furthermore, ex vivo cultures of human intestinal lamina propria mononuclear cells and iNKT cell clones from IBD patients with vancomycin pre-treated sterile fecal water showed a Th1/Th17 skewing in CD4+ T-cell populations; metronidazole, on the other hand, induced the polarization of iNKT cells toward the production of IL10. Conclusions Diverse antibiotic regimens affect the ability of the gut microbiota to control intestinal inflammation in experimental colitis by altering the microbial community structure and microbiota-derived metabolites.

Summary Members of the genus Pseudomonas inhabit diverse environments, such as soil, water, plants and humans. The variability of habitats is reflected in the diversity of the structure and composition of their genomes. This cosmopolitan bacterial genus includes species of biotechnological, medical and environmental importance. In this study, we report on the most relevant genomic characteristics of Pseudomonas sp. strain ABC1, a siderophore‐producing fluorescent strain recently isolated from soil. Phylogenomic analyses revealed that this strain corresponds to a novel species forming a sister clade of the recently proposed Pseudomonas kirkiae. The genomic information reveals an overrepresented repertoire of mechanisms to hoard iron when compared to related strains, including a high representation of fecI‐fecR family genes related to iron regulation and acquisition. The genome of the Pseudomonas sp. ABC1 contains the genes for non‐ribosomal peptide synthetases (NRPSs) of a novel putative Azotobacter‐related pyoverdine‐type siderophore, a yersiniabactin‐type siderophore and an antimicrobial betalactone; the last two are found only in a limited number of Pseudomonas genomes. Strain ABC1 can produce siderophores in a low‐cost medium, and the supernatants from cultures of this strain promote plant growth, highlighting their biotechnological potential as a sustainable industrial microorganism., ‘Pseudomonas chilensis’ strain ABC1 was fully sequenced. About 5% of the ABC1 genome is devoted to iron acquisition, including 37 ECF sigma factors. Strain ABC1 produces pyoverdine and has the genes for the production of yersiniabactin.

In March 2015, a patient in Colombia with HIV/AIDS was hospitalized for disseminated ulcers after milking cows that had vesicular lesions on their udders. Vaccinia virus was detected, and the case met criteria for progressive vaccinia acquired by zoonotic transmission. Adherence to an optimized antiretroviral regimen resulted in recovery. © 2020 Centers for Disease Control and Prevention (CDC). All rights reserved.

OBJECTIVES: To investigate differences in antibiotic prescription for patients with hard-to-heal ulcers assessed using a digital decision support system (DDSS) compared with those assessed without using a DDSS. A further aim was to examine predictors for antibiotic prescription. DESIGN: Register-based study. SETTING: In 2018-2019, healthcare staff in primary, community and specialist care in Sweden tested a DDSS that offers a mobile application for data and photograph transfer to a platform for multidisciplinary consultation and automatic transmission of data to the Registry of Ulcer Treatment (RUT). Register-based data from patients assessed and diagnosed using the DDSS combined with the RUT was compared with register-based data from patients whose assessments were merely registered in the RUT. PARTICIPANTS: A total of 117 patients assessed using the DDSS combined with the RUT (the study group) were compared with 1784 patients whose assessments were registered in the RUT without using the DDSS (the control group). PRIMARY AND SECONDARY OUTCOME MEASURES: The differences in antibiotic prescription were analysed using the Pearson's χ2 test. A logistic regression analysis was used to check for influencing factors on antibiotic prescription. RESULTS: Patients assessed using a DDSS in combination with the RUT had significantly lower antibiotic prescription than patients entered in the RUT without using the DDSS (8% vs 26%) (p=0.002) (only healed ulcers included). Predictors for antibiotic prescription were diabetes; long healing time; having an arterial, neuropathic or malignant ulcer. CONCLUSIONS: A DDSS with data and photograph transfer that enables multidisciplinary communication appears to be a suitable tool to reduce antibiotic prescription for patients with hard-to-heal ulcers. CC BY-NC 4.0© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.October 2022Correspondence to Dr Hanna Linnea Wickström; hanna.wickstrom@med.lu.seThe study was partly funded by the Scientific Committee of Blekinge County, Council's Research and Development Foundation as part of a PhD studentship (LTB-939727).

Medicinal plants have served as an important source for addressing the ailments of humans and animals alike. The emergence of advanced technologies in the field of drug discovery and development has helped in isolating various bioactive phytochemicals and developing them as drugs. Owing to their significant pharmacological benefits and minimum adverse effects, they not only serve as good candidates for therapeutics themselves but also help in the identification and development of related drug like molecules against various metabolic and infectious diseases. The ever-increasing diversity, severity and incidence of infectious diseases has resulted in an exaggerated mortality and morbidity levels. Geno-proteomic mutations in microbes, irrational prescribing of antibiotics, antimicrobial resistance and human population explosion, all call for continuous efforts to discover and develop alternated therapeutic options against the microbes. This review article describes the pharmacoinformatics tools and methods which are currently used in the discovery of bioactive phytochemicals, thus making the process more efficient and effective. The pharmacological aspects of the drug discovery and development process have also been reviewed with reference to the in silico activities. Communicated by Ramaswamy H. Sarma. © 2021 Informa UK Limited, trading as Taylor & Francis Group.

Antibiotics are often used in human and veterinary medicine for the treatment of bacterial diseases. However, extensive use of antibiotics in agriculture can result in the contamination of common food staples such as milk. Consumption of contaminated products can cause serious illness and a rise in antibiotic resistance. Conventional methods of antibiotics detection such are microbiological assays chromatographic and mass spectroscopy methods are sensitive; however, they require qualified personnel, expensive instruments, and sample pretreatment. Biosensor technology can overcome these drawbacks. This review is focused on the recent achievements in the electrochemical biosensors based on nucleic acid aptamers for antibiotic detection. A brief explanation of conventional methods of antibiotic detection is also provided. The methods of the aptamer selection are explained, together with the approach used for the improvement of aptamer affinity by post-SELEX modification and computer modeling. The substantial focus of this review is on the explanation of the principles of the electrochemical detection of antibiotics by aptasensors and on recent achievements in the development of electrochemical aptasensors. The current trends and problems in practical applications of aptasensors are also discussed. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. 1/0419/20; Horizon 2020 Framework Programme, H2020; H2020 Marie Skłodowska-Curie Actions, MSCA: 101007299; Kazan Federal University: PRIORITY-2030 Acknowledgments: G.E. acknowledges the support from the Kazan Federal University Strategic Academic Leadership Program (‘PRIORITY-2030’). Funding: T.H. acknowledges funding from the Science Grant Agency VEGA, project No.: 1/0419/20. This study was also funded under European Union’s Horizon 2020 research and innovation program through the Marie Skłodowska-Curie Grant Agreement No. 101007299.

Sporadic Legionnaires' disease is frequently detected in commercial truck drivers. We report 2 sporadic cases of this disease in Barcelona, Spain, that occurred during December 2019 and September 2020. Laboratory findings were consistent with windshield wiper fluid without added screen wash as a possible source of infection for both cases.

Background The World Health Organization now recommends the use of typhoid conjugate vaccines (TCVs) in typhoid-endemic countries, and Gavi, the Vaccine Alliance, added TCVs into the portfolio of subsidized vaccines. Data from the Severe Typhoid Fever in Africa (SETA) program were used to contribute to TCV introduction decision-making processes, exemplified for Ghana and Madagascar. Methods Data collected from both countries were evaluated, and barriers to and benefits of introduction scenarios are discussed. No standardized methodological framework was applied. Results The Ghanaian healthcare system differs from its Malagasy counterpart: Ghana features a functioning insurance system, antimicrobials are available nationwide, and several sites in Ghana deploy blood culture–based typhoid diagnosis. A higher incidence of antimicrobial-resistant Salmonella Typhi is reported in Ghana, which has not been identified as an issue in Madagascar. The Malagasy people have a low expectation of provided healthcare and experience frequent unavailability of medicines, resulting in limited healthcare-seeking behavior and extended consequences of untreated disease. Conclusions For Ghana, high typhoid fever incidence coupled with spatiotemporal heterogeneity was observed. A phased TCV introduction through an initial mass campaign in high-risk areas followed by inclusion into routine national immunizations prior to expansion to other areas of the country can be considered. For Madagascar, a national mass campaign followed by routine introduction would be the introduction scenario of choice as it would protect the population, reduce transmission, and prevent an often-deadly disease in a setting characterized by lack of access to healthcare infrastructure. New, easy-to-use diagnostic tools, potentially including environmental surveillance, should be explored and improved to facilitate identification of high-risk areas.

Background The use of antibiotic agents in the treatment of infectious diseases has greatly contributed to the decrease in morbidity and mortality, but these great advances in treatment are being undermined by the rapidly increasing antimicrobial resistant organisms. Extended-spectrum beta-lactamases are enzymes hydrolyzing the beta lactam antibiotics, including third generation cephalosporins and monobactams but not cephamycins and carbapenems. They pose a serious global health threat and have become a challenge for health care providers. The aim of this research was to assess the prevalence of extended-spectrum beta-lactamase producing Escherichia coli in University of Nigeria Teaching Hospital Ituku-Ozalla Enugu and to detect the risk factors for acquisition of the resistant organism. To proffer advice on antibiotic stewardship in clinical practice and public health interventions, to curb the spread of the resistant organisms in the hospital. Results Out of the 200 E. coli isolates, 70 (35.00%) were confirmed positive for extended-spectrum beta-lactamase production. Fifty-three (75.7%) were from hospital acquired infections. All the isolates were resistant to ampicillin, tetracycline and chloramphenicol while 68 (97.14%) of the 70 isolates were susceptible to imipenem. BlaTEM, blaSHV and blaTEM were detected in 66 (94%) of the 70 isolates. The ESBL bla genes detected were blaCTX-M (n = 26; 37.14%), blaTEM (n = 7; 10.00%), blaSHV (n = 2; 2.86%), blaCTX-M/TEM (n = 7; 10.0%), blaCTX-M/SHV (n = 14; 20.0%) and blaCTX-M/TEM/SHV (n = 10; 14.29%). The three bla genes were not detected in 4 (5.71%) of the isolates. Recent surgery, previous antibiotic and intensive care unit admission were the associated risk factors to infections caused by extended-spectrum beta-lactamase producing E. coli. Conclusion There is a high rate of infections caused by extended-spectrum beta-lactamase producing E. coli. Recent surgery, previous antibiotic and intensive care unit admission were associated risk factors.

Enteral energy delivery above requirements (overfeeding) is believed to cause adverse effects during critical illness, but the literature supporting this is limited. We aimed to quantify the reported frequency and clinical sequelae of energy overfeeding with enterally delivered nutrition in critically ill adult patients. A systematic search of MEDLINE, EMBASE, and CINAHL from conception to November 28, 2018, identified clinical studies of nutrition interventions in enterally fed critically ill adults that reported overfeeding in 1 or more study arms. Overfeeding was defined as energy delivery > 2000 kcal/d, > 25 kcal/kg/d, or ≥ 110% of energy prescription. Data were extracted on methodology, demographics, prescribed and delivered nutrition, clinical variables, and predefined outcomes. Cochrane "Risk of Bias" tool was used to assess the quality of randomized controlled trials (RCTs). Eighteen studies were included, of which 10 were randomized (n = 4386 patients) and 8 were nonrandomized (n = 223). Only 4 studies reported a separation in energy delivery between treatment groups whereby 1 arm met the definition of overfeeding, which reported no between-group differences in mortality, infectious complications, or ventilatory support. Overfeeding was associated with increased insulin administration (median 3 [interquartile range: 0-41.8] vs 0 [0-30.6] units/d) and upper-gastrointestinal intolerance in 1 large RCT and with duration of antimicrobial therapy in a small RCT. There are limited high-quality data to determine the impact of energy overfeeding of critically ill patients by the enteral route; however, based on available evidence, overfeeding does not appear to affect mortality or other important clinical outcomes.

The emergence of antimicrobial resistance is a significant public health issue worldwide, particularly for healthcare-associated infections caused by carbapenem-resistant gram-negative pathogens. Cefiderocol is a novel siderophore cephalosporin targeting gram-negative bacteria, including strains with carbapenem resistance. The structural characteristics of cefiderocol show similarity to both ceftazidime and cefepime, which enable cefiderocol to withstand hydrolysis by β-lactamases. The unique chemical component is the addition of a catechol moiety on the C-3 side chain, which chelates iron and mimics naturally occurring siderophore molecules. Following the chelation of iron, cefiderocol is actively transported across the outer membrane of the bacterial cell to the periplasmic space via specialized iron transporter channels. Furthermore, cefiderocol has demonstrated structural stability against hydrolysis by both serine- and metallo-β-lactamases, including clinically relevant carbapenemases such as Klebsiella pneumoniae carbapenemase, oxacillin carbapenemase-48, and New Delhi metallo-β-lactamase. Cefiderocol has demonstrated promising in vitro antibacterial and bactericidal activity, which correlates with its in vivo efficacy in several animal models. This article reviews the discovery and chemistry of cefiderocol, as well as some of the key microbiological and in vivo findings on cefiderocol from recently conducted investigations.

In recent decades, Neisseria gonorrhoeae has developed resistance to several antimicrobial classes. Molecular epidemiology approaches are useful for detecting emerging, often resistant, gonococcal ...

Although tertiary hospitals have successfully introduced ASPs by antimicrobial stewardship teams, lots of community hospitals without pediatric infectious disease specialists have difficulty implementing ASP. We present a successful implementation of simple and feasible NICU antimicrobial stewardship program in a Japanese community hospital.We developed a protocol of antimicrobial treatment in our NICU department and have implemented the protocol from September 2017. The protocol consists of start and stop of criteria antimicrobial treatment, weekend report of blood culture result from microbiology department and stopping ordering antimicrobials beforehand for the next day. We compared days of therapy (DOT) during the post-implementation period (September 2017 to August 2018) with that of pre-implementation period (March 2013 to August 2017).In pre- and post-ASP implementation periods, 913 and 194 patients were analyzed. DOT was 175.1 and 41.6/1000 patient-days, respectively (p 0.001) with 76.2% reduction. The percentage of neonates who had any antimicrobials and the percentage of prolonged antimicrobial treatments among neonates who had any antimicrobials decreased significantly (55.3% vs 20.6%, p 0.001 and 65.0% vs 32.5%, p 0.001). The protocol compliance rates were also significantly different (55.4% vs 95.4%; p 0.001). The methicillin-resistant rate of S.aureus rates were significantly reduced in post-ASP period (31.1% vs 12.9%; p = 0.002).This ASP program was easily implemented in a NICU department of a community hospital and significantly reduced antimicrobial prescription. This kind of simple protocol may be successfully scaled-up in resource limited community hospitals without no pediatric infectious disease specialists or antimicrobial stewardship team.

Background Complications from typhoid fever disease have been estimated to occur in 10%–15% of hospitalized patients, with evidence of a higher risk in children and when delaying the implementation of effective antimicrobial treatment. We estimated the prevalence of complications in hospitalized patients with culture-confirmed typhoid fever and the effects of delaying the implementation of effective antimicrobial treatment and age on the prevalence and risk of complications. Methods A systematic review and meta-analysis were performed using studies in the PubMed database. We rated risk of bias and conducted random-effects meta-analyses. Days of disease at hospitalization (DDA) was used as a surrogate for delaying the implementation of effective antimicrobial treatment. Analyses were stratified by DDA (DDA Results The pooled prevalence of complications estimated among hospitalized typhoid fever patients was 27% (95% CI, 21%–32%; I2 = 90.9%, P < .0001). Patients with a DDA ≥ 10 days presented higher prevalence (36% [95% CI, 29%–43%]) and three times greater risk of severe disease (OR, 3.00 [95% CI, 2.14–4.17]; P < .0001) than patients arriving earlier (16% [95% CI, 13%– 18%]). Difference in prevalence and risk by age groups were not significant. Conclusions This meta-analysis identified a higher overall prevalence of complications than previously reported and a strong association between duration of symptoms prior to hospitalization and risk of serious complications.

Background Uganda is among the 51 countries where cholera outbreaks are common with epidemics occurring predominantly along the western border with Democratic Republic of Congo (DRC), Kampala city slums, Busia district which is a border town with Western Kenya, Mbale district and the Karamoja Sub-region. This report summarizes findings from the epidemiologic investigation, which aimed at identifying the mode of transmission and antibiotic susceptibility patterns of the Vibrio cholerae isolated in Kasese district, Uganda. Methods A descriptive cross-sectional study was carried out between 2017 and 2018 to describe the epidemiology of the cholera epidemic in Kasese district, Uganda. Rectal swabs were collected from 69 suspected case-persons and cultured on Thiosulphate-Citrate-Bile-Salts Sucrose (TCBS™; SEIKEN Japan) agar and incubated at 37 °C for 18–24 h. The isolates were serotyped with polyvalent 01 antiserum and monovalent serotype Inaba and Ogawa antisera (Denka Seiken, Tokyo, Japan) to determine which serotype was responsible for the outbreak. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method on Mueller-Hinton agar. A list of discharged patients was obtained from the isolation units of Bwera hospital and Kagando hospital and the individuals were followed to the community where they live. Questionnaires were administered to a total of 75 participants who were either the cases or relatives to the case. GPS points of the homes of the cases and pictures of potential source infection were also taken and cases were mapped. Results A total of 222 cases were recorded in the Kasese District outbreak between the month of September 2017 and January 2018 with the case fatality rate (CFR) of 1.4%. Children below the age of 14 years contributed the biggest proportion of the cases (70%) and out of these, 33% were aged below 5 years. Culture isolated 69 V. cholerae 01 serotype Inaba from the total of 71 samples. Salmonella typhi was Isolated from the other two samples which were negative for V. cholerae. Antibiotic susceptibility using Kirby-Bauer disc diffusion method was done on isolates from 69 participants and showed 100% resistance to Ampicillin and over 50% were resistant to trimethoprim/Sulfamethoxazole whereas gentamicin showed 100% susceptibility. Environmental assessment revealed rampant cases of open defecation. Conclusion Though we did not culture water to confirm contamination with Vibrio cholerae, we hypothesize that the cholera epidemic in Kasese 2017 was sparked off by consumption of contaminated water following the heavy floods that washed away latrines into water sources in Bwera, Isango and Nakiyumbu sub-counties. V. cholerae was also highly resistant to the commonly used antibiotics.

Leishmania parasites are the causative agents of a wide spectrum of human diseases. The clinical manifestations of leishmaniasis range from self-healing skin lesions to fatality. The World Health Organization has classed leishmaniasis as a category 1 neglected tropical disease. Leishmaniasis represents a major international health challenge, affecting 12 million people per year and with nearly 310 million people at risk. The first-line chemotherapies used to treat leishmaniasis are intravenous pentavalent antimonials; however, these drugs are highly toxic. As the use of oral treatment options such as paromomycin and miltefosine has increased, the incidence of disease relapse has increased and drug resistance to antimonials has developed, emphasizing the importance of identifying new chemotherapies. A novel, target-free fluorometric high-throughput screen with an average Z-score of 0.73 +/- 0.13 has been developed to identify small molecules with antileishmanial activity. Screening of 10,000 small molecules from the ChemBridge DIVER-set™ library cassette #5 yielded 210 compounds that killed 80% of parasites, resulting in a hit rate of 2.1%. One hundred and nine molecular scaffolds were represented within the hit compounds, and one scaffold that exhibited potent antileishmanial activity was 2,4-diaminoquinazoline. Host cell toxicity was determined prior to in-vitro infection of human THP-1 macrophages with Leishmania donovani mCherry expressing promastigotes; successful drug treatment was considered when the half maximal inhibitory concentration was10 µM. BALB/c mice were infected with Leishmania major mCherry promastigotes and treated with small molecules that were successful during in-vitro infections. Several small molecules tested were as efficacious at resolving cutaneous leishmaniasis lesions in mice as known antimonial treatments.

Background: Complicated urinary tract infection (cUTI) is often associated with drug-resistant pathogens and requires therapy with broad-spectrum antibiotics. Choice of empiric therapy should be based on an evaluation of clinical efficacy and medical costs. We used a cost-utility model to compare the empiric use of a new antibiotic, ceftolozane/tazobactam with piperacillin/tazobactam in patients with cUTI. Methods: The analysis was conducted using a decision tree and patient-level simulation approach. Patients in the model received empiric antibiotic treatment with ceftolozane/tazobactam or piperacillin/tazobactam. Outcomes included mortality, medical costs and quality-adjusted life years (QALYs). Parameters related to pathogen distribution, length of hospital stay and medical costs, were estimated based on a cohort of patients with cUTI admitted during July 1st, 2015 to August 31st, 2016 to the National Taiwan University Hospital, a teaching hospital in Taiwan. Isolates used for the patient-level simulation to determine susceptibility to either drug were taken from the Study for Monitoring Antimicrobial Resistance Trend database. Results: The analysis was performed on a simulation of 1000 patients. Empiric use of ceftolozane/tazobactam leads to higher total medical costs (USD 4199.01 per patient versus USD 3594.76, respectively) but also more discounted QALYs (4.80 versus 4.78, respectively). The additional cost per discounted QALY gained associated with empiric ceftolozane/tazobactam was 32,521.08 USD (956,282 NTD). Conclusions: Our results suggest that empiric use of ceftolozane/tazobactam for the treatment of cUTI could be a cost-effective choice in Taiwan. Keywords: Complicated urinary tract infection, Ceftolozane/tazobactam, Piperacillin/tazobactam, Cost-effectiveness analysis, Cost-utility analysis

Background Several reports designate the recent increase in community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) nasal carriage. Because of the scanty information regarding the nasal carriage sate of MRSA in the west of Iran, the purpose of the present study was to determine the frequency of CA-MRSA in Sanandaj city. Methods Swabs collected from anterior nares of 600 volunteers were analyzed for the presence of S. aureus. The isolates were further investigated for methicillin resistance by using the cefoxitin disk diffusion test, followed by PCR-amplification of the mecA gene. SCCmec types and the presence of the Panton-Valentine Leukocidin (pvl) encoding genes were determined through PCR. Finally, the antimicrobial susceptibility of the isolates was determined by the agar diffusion method. Results Nasal screening identified 181 S. aureus, of which 55 isolates were MRSA. SCCmec types IV and V were detected in MRSA at frequencies of 80 and 20%, respectively. The overall frequency of pvl genes among the MRSA isolates was 14.54%. MRSA isolates were highly susceptible (98.18%) to mupirocin, gentamicin, and fusidic acid. Conclusions The high prevalence of CA-MRSA carriage in the population could pose a serious public health concern for the region. Additionally, advent of drug-resistant pvl-positive strains demands continuous surveillance on the colonization state of CA-MRSA in order to prevent dissemination of the bacterium in the community.

In recent years, high frequencies of trimethoprim resistance in urinary tract infections (UTIs) caused by E. coli are have been reported. Co-resistance to other antimicrobial drugs may play a role in this increase. Therefore, we investigated whether previous use of other antimicrobial drugs was associated with trimethoprim resistance. We conducted a nested case-control study with urinary cultures with E. coli from participants of the Rotterdam Study sent in by general practitioners to the regional laboratory between 1 January 2000 and 1 April 2016. Multivariable logistic regression analysis was performed to study the association between prior prescriptions of several antimicrobial drug groups and trimethoprim resistance using individual participant data. Urinary cultures of 1264 individuals with a UTI caused by E. coli were included. When adjusted for previous other antimicrobial drug use, a history of > 3 prescriptions of extended-spectrum penicillins (OR 1.68; 95% CI 1.10–2.55) was significantly associated with trimethoprim resistance of E. coli as was the use of > 3 prescriptions of sulfonamides and trimethoprim (OR 2.22; 95% CI 1.51–3.26). The use of > 3 prescriptions of nitrofuran derivatives was associated with a lower frequency of trimethoprim resistance (OR 0.60; 95% CI 0.39–0.92), after adjustment for other antimicrobial drug prescriptions. We found that previous use of extended-spectrum penicillins is associated with trimethoprim resistance. On the contrary, previous nitrofurantoin use was associated with a lower frequency of trimethoprim resistance. Especially in individuals with recurrent UTI, co-resistance should be taken into account and susceptibility testing before starting trimethoprim should be considered. Electronic supplementary material The online version of this article (10.1007/s10096-019-03672-2) contains supplementary material, which is available to authorized users.

Background Bacterial meningitis is a major cause of mortality among children under 5 years of age. Senegal is part of World Health Organization–coordinated sentinel site surveillance for pediatric bacterial meningitis surveillance. We conducted this analysis to describe the epidemiology and etiology of bacterial meningitis among children less than 5 years in Senegal from 2010 and to 2016. Methods Children who met the inclusion criteria for suspected meningitis at the Centre Hospitalier National d’Enfants Albert Royer, Senegal, from 2010 to 2016 were included. Cerebrospinal fluid specimens were collected from suspected cases examined by routine bacteriology and molecular assays. Serotyping, antimicrobial susceptibility testing, and whole-genome sequencing were performed. Results A total of 1013 children were admitted with suspected meningitis during the surveillance period. Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus accounted for 66% (76/115), 25% (29/115), and 9% (10/115) of all confirmed cases, respectively. Most of the suspected cases (63%; 639/1013) and laboratory-confirmed (57%; 66/115) cases occurred during the first year of life. Pneumococcal meningitis case fatality rate was 6-fold higher than that of meningococcal meningitis (28% vs 5%). The predominant pneumococcal lineage causing meningitis was sequence type 618 (n = 7), commonly found among serotype 1 isolates. An ST 2174 lineage that included serotypes 19A and 23F was resistant to trimethoprim-sulfamethoxazole. Conclusions There has been a decline in pneumococcal meningitis post–pneumococcal conjugate vaccine introduction in Senegal. However, disease caused by pathogens covered by vaccines in widespread use still persists. There is need for continued effective monitoring of vaccine-preventable meningitis., Disease caused by pathogens covered by conjugate vaccines in widespread use still persists in Senegal. There is need for continued effective monitoring of vaccine-preventable meningitis.

Background Meningitis is endemic in Niger. Haemophilus influenzae type b (Hib) vaccine and the 13-valent pneumococcal conjugate vaccine (PCV13) were introduced in 2008 and 2014, respectively. Vaccination campaign against Neisseria meningitidis serogroup A was carried out in 2010–2011. We evaluated changes in pathogen distribution using data from hospital-based surveillance in Niger from 2010 through 2016. Methods Cerebrospinal fluid (CSF) specimens from children, Numbers of Streptococcus pneumoniae meningitis decreased following 13-valent pneumococcal conjugate vaccine introduction in 2014. The case fatality rate of S. pneumoniae meningitis was higher compared with both Haemophilus influenzae and Neisseria meningitidis meningitis. Increased importance of N. meningitidis serogroup C was observed.

Background Meningitis is endemic to regions of Cameroon outside the meningitis belt including the capital city, Yaoundé. Through surveillance, we studied the etiology and molecular epidemiology of pediatric bacterial meningitis in Yaoundé from 2010 to 2016. Methods Lumbar puncture was performed on 5958 suspected meningitis cases; 765 specimens were further tested by culture, latex agglutination, and/or polymerase chain reaction (PCR). Serotyping/grouping, antimicrobial susceptibility testing, and/or whole genome sequencing were performed where applicable. Results The leading pathogens detected among the 126 confirmed cases were Streptococcus pneumoniae (93 [73.8%]), Haemophilus influenzae (18 [14.3%]), and Neisseria meningitidis (15 [11.9%]). We identified more vaccine serotypes (19 [61%]) than nonvaccine serotypes (12 [39%]); however, in the latter years non–pneumococcal conjugate vaccine serotypes were more common. Whole genome data on 29 S. pneumoniae isolates identified related strains (, We studied the etiology of pediatric bacterial meningitis in Cameroon, in the postvaccine era, associated with Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. Our findings emphasize the need for increased efforts to alleviate vaccine-preventable disease in our subregion.

In the light of pandemic spreads of multi-drug-resistant micro-organisms, alternative antimicrobial strategies to the use of antibiotics are the focus of research attention. As a prerequisite for medical application, the aim of this study was to develop a three-dimensional full skin infection model to evaluate the bioactivity and biocompatibility of antiseptics in application-relevant concentrations. A three-dimensional (3D) full skin model consisting of collagen-embedded fibroblasts as dermis and a fully differentiated epidermis built from keratinocytes was infected with Staphylococcus aureus. Infected skin models were treated for 24 h with the antiseptics polihexanide, octenidine dihydrochloride, chlorhexidine digluconate and povidone-iodine. Infection resulted in detrimental effects, a strong immune response with increased secretion of lactate dehydrogenase and pro-inflammatory cytokines, and increased gene expression of pro-inflammatory cytokines and antimicrobial peptides after 24 h. Application of antiseptics protected the skin models from damage due to S. aureus infection while demonstrating good biocompatibility. The best ratio of bioactivity to biocompatibility was observed for polihexanide. Polihexanide also enhanced the innate immune response by increasing the gene expression levels of antimicrobial peptides such as human β-defensin 2, human β-defensin 3, psoriasin and ribonuclease 7. The developed model provides an excellent tool to investigate the response of human cells to microbial infections in a complex 3D structure. Furthermore, the infection model is appropriate for evaluation of bioactivity and biocompatibility of antiseptics. As such, the model presented in this study is a promising approach to evaluate the mechanisms and effectiveness of new antimicrobial strategies.

Penicillinase-producing Neisseria gonorrhoeae (PPNG) expressing the TEM β-lactamase variant TEM-135 are a global public-health concern as this variant requires only a single amino acid substitution to develop into an extended-spectrum β-lactamase. The aim of this study was to investigate the epidemiology of blaTEM-135 in 505 N. gonorrhoeae isolates from Hangzhou, China, during the periods 2011-2012 and 2015-2017. Investigation by nitrocefin test and mismatch amplification PCR showed that 41.0% (207/505) of the isolates were PPNG, of which 37.2% (77/207) contained the blaTEM-135 gene. Further PCR-based plasmid typing showed that blaTEM-135 was predominantly expressed from the Asian plasmid (94%). PPNG isolates consisted of three major clusters, namely Asian plasmid/blaTEM-135 (34.8%), Asian plasmid/blaTEM-1 (32.4%) and African plasmid/blaTEM-1 (28.0%), which showed significant differences in penicillin minimum inhibitory concentrations (MICs) determined by the agar dilution method. Representative isolates were investigated by quantitative real-time PCR (plasmid copy number and blaTEM gene expression), western blot analysis (TEM levels and TEM stability) and in vivo β-lactamase activity assays to elucidate the cause of the observed differences in penicillin MIC. Overall, isolates of the Asian plasmid/blaTEM-135 cluster showed the highest β-lactamase activity, which was explained by higher blaTEM gene expression (Asian versus African plasmid) and higher TEM stability (TEM-135 versus TEM-1). In conclusion, the blaTEM-135 gene is commonly present on the Asian plasmid in PPNG isolates from Hangzhou. The PPNG isolate cluster containing the Asian plasmid and blaTEM-135 showed the highest penicillin MICs, which might explain its abundance in the Hangzhou population.

The aim of this study was to describe the population pharmacokinetics of ticarcillin during extended daily diafiltration (EDDf) in critically ill patients with acute kidney injury. Blood samples were collected from critically ill patients prescribed ticarcillin during one to two dosing intervals during which EDDf was performed. Plasma samples were measured using a validated ultra high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method. Concentration–time data were analysed using a population pharmacokinetics approach with Pmetrics®. A total of 53 blood samples were collected from six critically ill patients (three male). The mean ± standard deviation patient age, weight and body mass index (BMI) was 43 ± 22 years, 88 ± 14 kg and 31 ± 5 kg/m2, respectively. A two-compartment linear model adequately described the data. Median population pharmacokinetic parameter estimates were as follows: clearance in the presence of EDDf (CLEDDf), 6.41 L/h; clearance of EDDf (CLnon-EDDf), 4.97 L/h; volume of distribution of the central compartment (Vc), 56.46 L; intercompartmental clearance from the central to peripheral compartment (kCP), 13.54 L/h; and intercompartmental clearance from the peripheral to central compartment (kPC), 21.93 L/h. This is the first population pharmacokinetic model of ticarcillin in patients receiving EDDf. Large pharmacokinetic variability was found, supporting further investigation of the pharmacokinetics of less-studied β-lactam antibiotics in prolonged intermittent renal replacement therapy.

Objectives Most vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) are derived from hospital-associated MRSA due to treatment failure; however, the prevalence of hVISA/VISA in community settings remains unclear. Methods Four hundred and seventy-six community-associated isolates were collected between 2010 and 2011 during national surveillance for antimicrobial resistance in 31 county hospitals across China. Drug susceptibility evaluation and mecA detection were performed by using broth microdilution and PCR analysis, respectively. hVISA/VISA were identified by using macro-Etest and a modified population analysis profile (PAP)-AUC method. The genetic features of all hVISA/VISA isolates were genotyped. Results Among 476 isolates, MRSA and MSSA accounted for 19.7% (n = 94) and 80.3% (n = 382), respectively. Two VISA and 36 hVISA isolates were identified by PAP-AUC testing. The VISA isolates and 29 of the hVISA isolates were MRSA. The proportion of hVISA/VISA was significantly higher in MRSA (30.9%) than in MSSA (1.8%). The hVISA/VISA isolates were assigned to 18 STs classified into seven clonal complexes (CCs). CC121 (n = 12) followed by ST239 (n = 11) was the most prevalent hVISA/VISA clone. All ST239-hVISA/VISA were MRSA, while 12 CC121-hVISA isolates included 6 MSSA and 6 MRSA isolates. SCCmec III was predominant among MRSA-hVISA/VISA isolates. agr I and agr IV were detected in ST239 and CC121, respectively. All except two strains were positive for Panton–Valentine leucocidin genes. Conclusions To the best of our knowledge, this is the first report of CC121 as a prevalent hVISA clone in community settings, highlighting the necessity of surveillance and stricter infection control measures for this globally disseminated lineage.

Background: Throughout the world multi drug resistant nosocomial infections are one of the leading causes of death and morbidity among hospitalized patients. Antimicrobial resistance [AMR] has become a major problem in treatment of such infections. High consumption of antimicrobials particularly in ICUs is often described as the most important factor leading to AMR. Objective: The aim of the study was to study the magnitude of antimicrobial resistance amongst nosocomial pathogens and the antimicrobial prescription patterns of patients admitted in intensive care unit. Methods: The study was conducted in I.C.U of a tertiary care government hospital in Delhi over a period of 4 months, on 100 patients admitted in I.C.U. Depending on clinical suspicion laboratory samples were collected and subjected to antimicrobial sensitivity testing. Antimicrobial prescription of these patients were collected from I.C.U records and analyzed. Observations: Staphylococcus aureus and Klebsiella species were the most common organism [23%]. Among patients where causative organism was isolated, two or more organisms were isolated from 50% of the samples. Most of the Klebsiella species and Acinetobacter species were resistant to beta lactam group of antibiotics such as cephalosporins and piperacillin-tazobactam. 60% of isolates of S. aureus were found to be MRSA while none of the S. aureus were resistant to linezolid and vancomycin. All patients were prescribed two or more antimicrobials while 66% patients were prescribed 3–5 antimicrobials. Commonest combination was beta lactam with metronidazole followed by levofloxacin with metronidazole with addition of aminoglycosides or linezolid as third drug. Total 20 antimicrobial agents were used in the treatment of the patients. Among these consumption [in DDD/100bed days] of metronidazole was highest [100.9] followed by fluconazole [76.6] and levofloxacin [62.7]. Conclusion: High usage of antimicrobial consumption has been noted in this study, prompting institution of measures to formulate and adherence to antimicrobial policy strictly. Keywords: Antimicrobial resistance, Antimicrobial consumption, I.C.U, DDD{defined daily dosage of antimicrobials}, DDD/100bed days

Background First-line antifungal treatment for invasive mucormycosis (IM) consists of liposomal amphotericin B. Salvage treatment options are limited and often based on posaconazole oral suspension. With the approval of posaconazole new formulations, patients could benefit from improved pharmacokinetics, safety and tolerability. Objectives Our aim was to assess the effectiveness of posaconazole new formulations for IM treatment. Methods We performed a case-matched analysis with proven or probable IM patients from the FungiScope® Registry. First-line posaconazole new formulations (1st-POSnew) and first-line amphotericin B plus posaconazole new formulations (1st-AMB+POSnew) cases were matched with first-line amphotericin B-based (1st-AMB) treatment controls. Salvage posaconazole new formulations (SAL-POSnew) cases were matched with salvage posaconazole oral suspension (SAL-POSsusp) controls. Each case was matched with up to three controls (based on severity, haematological/oncological malignancy, surgery and/or renal dysfunction). Results Five patients receiving 1st-POSnew, 18 receiving 1st-AMB+POSnew and 22 receiving SAL-POSnew were identified. By day 42, a favourable response was reported for 80.0% (n = 4/5) of patients receiving 1st-POSnew, for 27.8% (n = 5/18) receiving 1st-AMB+POSnew and for 50.0% (n = 11/22) receiving SAL-POSnew. Day 42 all-cause mortality of patients receiving posaconazole new formulations was lower compared with controls [20.0% (n = 1/5) in 1st-POSnew versus 53.3% (n = 8/15) in 1st-AMB; 33.3% (n = 6/18) in 1st-AMB+POSnew versus 52.0% (n = 26/50) in 1st-AMB; and 0.0% (n = 0/22) in SAL-POSnew versus 4.4% (n = 2/45) in SAL-POSsusp]. Conclusions Posaconazole new formulations were effective in terms of treatment response and associated mortality of IM. While posaconazole new formulations may be an alternative for treatment of IM, the limited sample size of our study calls for a cautious interpretation of these observations.

The aim of this study is to see the frequency, clinical presentation, and therapeutic response of extensively drug-resistant Salmonella enterica serovar Typhi and current susceptibility pattern of typhoidal Salmonella strains in our setup. This study was carried out at the Department of Medical Microbiology and Immunology and Department of Medicine, Pakistan Navy Ship (PNS) Shifa Hospital, Karachi, from January 1 to December 31, 2018. All the blood culture samples of patients (indoor and outdoor) with suspicion of enteric fever were processed. Isolates were cultured and identified using standard microbiological procedures. The antimicrobial sensitivity against the typhoidal Salmonellae was determined using Kirby-Bauer disc diffusion method as per the guidelines of Clinical and Laboratory Standards Institute (2018) and all the extensively drug-resistant (XDR) isolates were confirmed by Vitek 2 system. Clinical presentation and response to treatment of patients were followed. A total of 292 typhoidal Salmonella isolates were cultured. Resistance to ciprofloxacin against both Salmonella Typhi and Salmonella Paratyphi A was found to be very high (91%). Percentage of multidrug-resistant (MDR) isolates in Salmonella Typhi was 76% (182 isolates) and in Salmonella Paratyphi it was 34% (18 isolates). XDR isolates in Salmonella Typhi were significant that is 48% (115 isolates). Only 10 cases were given azithromycin who responded to treatment in mean 4.3 days. Out of 115 cases of XDR Salmonella Typhi, 103 patients were given parenteral meropenem and clinical response was seen in mean 5 days. The emergence and rapid spread of extensively drug-resistant Salmonella Typhi is alarming and highlights the significance of strict antimicrobial susceptibility surveillance programs with antimicrobial stewardship.

INTRODUCTION: Despite modern advances, the primary cause of death after burns remains infection and sepsis. A key factor in determining outcomes is colonization with multi-drug resistant (MDR) organisms. Infections secondary to MDR organisms are challenging due to lack of adequate antibiotic treatment, subsequently prolonging hospital stay and increasing risk of adverse outcomes. AREAS COVERED: This review highlights the most frequent organisms colonizing burn wounds as well as the most common MDR bacterial infections. Additionally, we discuss different treatment modalities and MDR infection prevention strategies as their appropriate management would minimize morbidity and mortality in this population. We conducted a search for articles on PubMed, Web of Science, Embase, Cochrane, Scopus and UpToDate with applied search strategies including a combination of: “burns, “thermal injury,” “infections,” “sepsis,” “drug resistance,” and “antimicrobials.” EXPERT OPINION: Management and prevention of MDR infections in burns is an ongoing challenge. We highlight the importance of preventative over therapeutic strategies, which are easy to implement and cost-effective. Additionally, targeted, limited use of antimicrobials can be beneficial in burn patients. A promising future area of investigation within this field is post-trauma microbiome profiling. Currently, the best treatment strategy for MDR in burn patients is prevention.

Objectives To assess the prevalence, antimicrobial susceptibilities and molecular characteristics of ESBL-producing Escherichia coli and Klebsiella pneumoniae infecting patients receiving care in Canadian hospitals from January 2007 to December 2016. Methods Clinical isolates of E. coli (n = 8387) and K. pneumoniae (n = 2623) submitted to CANWARD, an ongoing Canadian national surveillance study, were tested using the CLSI reference broth microdilution method to determine their susceptibility to 15 antimicrobial agents. ESBL-producing E. coli and K. pneumoniae confirmed by the CLSI phenotypic method and putative AmpC-producing E. coli underwent PCR testing and DNA sequencing to identify resistance genes. Annual proportions of isolates harbouring ESBL and AmpC genes were assessed by the Cochran–Armitage test of trend. Results The annual proportion of isolates of E. coli that were ESBL producing increased from 3.4% in 2007 to 11.1% in 2016 (P 95% of ESBL-producing E. coli were susceptible to amikacin, colistin, ertapenem, meropenem and tigecycline. The proportion of isolates of K. pneumoniae that were ESBL producing increased from 1.3% in 2007 to 9.7% in 2016 (P 95% of ESBL-producing K. pneumoniae were susceptible to amikacin and meropenem. CTX-M-15 was the predominant genotype in both ESBL-producing E. coli (64.2% of isolates) and ESBL-producing K. pneumoniae (51.0%). The annual proportion of isolates of E. coli that were AmpC producing [annual proportion mean 1.9% (range 0.3%–3.1%)] was unchanged from 2007 to 2016 (P > 0.5). Conclusions The prevalence of both ESBL-producing E. coli and K. pneumoniae increased significantly in Canada during the study period while the prevalence of AmpC-producing E. coli remained low and stable.

Summary Background Healthcare-associated infections (HAIs) are among the most common adverse events in patient care, and account for substantial morbidity and mortality. Aim To obtain the first estimates of the current prevalence of HAIs and antimicrobial resistance in acute care hospitals in Kyiv, Ukraine. Methods Prospective surveillance was conducted from January 2014 to December 2016 in five acute care hospitals in Kyiv. Definitions of HAIs were adapted from the Centers for Disease Control and Prevention's National Healthcare Safety Network. Findings Among 53,884 patients, 3753 (7%) HAIs were observed. The most frequently reported HAIs were respiratory tract infections (pneumonia 19.4%, lower respiratory tract infections 4.1%), surgical site infections (19.6%), urinary tract infections (17.5%) and bloodstream infections (10.6%). Death during hospitalization was reported in 7.2% cases of HAI. The micro-organisms most frequently isolated from HAIs were Escherichia coli (15.9%), Staphylococcus aureus (14.8%), Enterococcus spp. (10.2%), Pseudomonas aeruginosa (8.9%) and Klebsiella spp. (8.9%). Meticillin resistance was reported in 28.2% of S. aureus, and 14.2% of enterococci were resistant to vancomycin. Overall, 35.1% of all Enterobacteriaceae were resistant to third-generation cephalosporins, with the highest resistance rates seen in K. pneumoniae (53.8%) and E. coli (32.1%). Conclusions Infection control priorities in hospitals should include prevention of surgical site infections, pneumonia, bloodstream infections and urinary tract infections. These results may help to delineate the requirements for infection prevention and control in acute care hospitals.

Background Skin antisepsis occurs in every healthcare environment. From basic hand hygiene, to antiseptic bathing and pre surgical care with alcohol/chlorhexidine, use of antimicrobial agents to reduce the skin microflora has skyrocketed in the past several years. Although used in hopes of reducing the likelihood of infection in patients, many products have been identified as the source of infection in several outbreaks, sometimes due to the nonsterile nature of the many readily available antiseptics. Body Intrinsic contamination of antiseptics during the manufacturing process is common. In fact, since the majority of these products are sold as nonsterile, they are allowed some level of microbial contamination based on the United States Pharmacopeia documents 61 and 62. Unfortunately, sometimes this contamination is with microorganisms resistant to the antiseptic and/or with those pathogenic to humans. In this scenario, healthcare-associated infections may occur, leaving the patient at higher risk of mortality and increasing costs of care substantially. Although antibiotic stewardship programs throughout the world suggest targeting use of antibiotics to limit resistance, few healthcare environments include other antimicrobial agents (such as antiseptics) in their programs. Conclusion Due to the potential for contamination with pathogenic organisms and the increased likelihood of selecting for resistant organisms with widespread use of broad-spectrum agents with non-specific mechanisms of action, a discussion around including skin antiseptics in stewardship programs is necessary, particularly those labeled as nonsterile. At minimum, debating the pros and cons of targeting use of daily antiseptic bathing in hospitalized patients should occur. Through mindfully incorporating any antimicrobial agent, sterile or not, into our repertoire of anti-infectives, we can save patient lives, reduce infection, and save costs.

There are very limited data on ticarcillin-clavulanate elimination by haemofiltration. We measured in vitro ticarcillin-clavulanate adsorption to polyacrylonitrile (PAN) filters and the sieving coefficient using a well-described bench model of haemofiltration. The dose of ticarcillin-clavulanate was 60/2 mg or 180/3 mg, and 0 or 12 g albumin was added to the 1 L of circulating blood-crystalloid mixture to produce four different experimental conditions. The experiment was repeated four times under each condition. Median (interquartile range [IQR] ) ticarcillin adsorption varied from 28 (27-30) mg to 85 (78-90) mg. Adsorption was increased when the dose of ticarcillin was higher (P

The efficacy and safety of short-course intravenous (i.v.) antimicrobial therapy for bloodstream infections is unknown. Therefore, a retrospective 8-year cohort study including 1431 hospitalised adults was conducted to compare the outcomes of patients receiving short-course (5–10 days) and long-course (11–16 days) i.v. antibiotic therapy for community-onset bacteraemia. Of 1010 patients who received short-course therapy, 726 were matched with 363 patients in the long-course group through propensity score matching at a ratio of 1:2 based on independent predictors of 30-day mortality identified in the multivariate regression model. Following appropriate matching, similarities between the two groups in the proportion of baseline characteristics (age, sex, major co-morbidities, co-morbidity severity, bacteraemia severity at onset and major bacteraemia sources) and 30-day crude mortality rate after bacteraemia onset were observed. Notably, clinical outcomes within 30 days after the end of i.v. therapy, in terms of proportions of post-treatment overall infections (2.2% vs. 6.1%; P = 0.001), infections caused by antimicrobial-resistant pathogens (ARPs) (1.7% vs. 4.4%; P = 0.007), and thereby post-treatment crude mortality (1.4% vs. 3.6%; P = 0.009), were lower in the short-course group. In conclusion, for adults with community-onset uncomplicated bacteraemia, short-course (5–10 days) i.v. antibiotic treatment did not result in an increased risk of mortality but instead decreased the odds of overall and ARP infections after the treatment course.

What is known and objective The overuse and misuse of antibiotics, especially for viral, and self‐limiting, respiratory tract infections such as sore throat, increases the risk of the development and spread of antimicrobial resistance within communities. Up to 80% of sore throat cases have a viral aetiology, and even when the infection is bacterial, most cases resolve without antibiotics. However, antibiotics are still frequently and often inappropriately prescribed for the treatment of sore throat. Furthermore, topical (local) antibiotics for treatment of sore throat are widely available over the counter. The objective of this systematic review was to establish the evidence for the benefits, risk of harm and antimicrobial resistance associated with topical (local) antibiotics used for patients with sore throat. Methods Eligible studies included those in patients with sore throat of any aetiology receiving the topical (local) antibiotics tyrothricin, bacitracin, gramicidin or neomycin where the antibiotic was topically/locally applied via the nasal cavity or throat. Nasal applications were included as these are occasionally used to treat upper respiratory tract infections that may involve sore throat. There was no restriction or requirement regarding comparator. The outcomes of interest included efficacy, safety, and in vitro culture and antimicrobial resistance data. Results and discussion This systematic review found sparse and mainly poor‐quality evidence relating to the use of topical (local) antibiotics for sore throat, and it was not possible to establish the benefits, risk of harm or impact of use on antimicrobial resistance. What is new and conclusions Further research is necessary to ascertain the risks and benefits of topical (local) antibiotics, their contribution to antimicrobial resistance and the risk of harm. We do, however, question whether it is appropriate and rational to use topical (local) antibiotics for the treatment of sore throat caused by respiratory tract infections in the absence of robust evidence.

Although the frequency of bone and joint infections caused by Enterobacter spp. is increasing, studies regarding the optimal antibiotic therapy are scarce. The objective of this retrospective study was to assess the clinical outcomes and safety of a fluoroquinolone-cotrimoxazole combination for the treatment of bone and joint infections caused by Enterobacter cloacae. Between 2010 and 2017, 30 patients with bone and joint infections caused by E. cloacae were treated with a fluoroquinolone-cotrimoxazole combination for 8-12 weeks. There were 26 cases (87%) of infection of an internal fixation device, two cases (6.6%) of pseudarthrosis with chronic osteomyelitis, and two cases (6.6%) of infection of knee and ankle prosthetic devices. The cure rate of the fluoroquinolone-cotrimoxazole combination was 80% by intention-to-treat analysis, with a mean follow-up of 29.3 ± 19.1 months. The fluoroquinolone-cotrimoxazole combination for 8-12 weeks is effective for the treatment of bone and joint infections caused by E. cloacae.

Summary Molecular assays may constitute a valid method for timely prediction of antimicrobial resistance and optimization of empirical antibiotic therapies. This study assessed ELITe MGB assays of blood cultures to detect the main carbapenemase and extended-spectrum beta-lactamase (ESBL) genes, Staphylococcus aureus and mec genes in less than 3 h. Excellent agreement was found between the results of genotypic and conventional phenotypic approaches. Retrospective analysis of medical records revealed that approximately 50% of bloodstream infections caused by ESBL-producing Enterobacteriaceae, carbapenemase-producing Enterobacteriaceae or meticillin-resistant S. aureus were initially treated with inactive drugs. Overall, 36.3% of patients could have been treated with appropriate therapy at least 24 h earlier if molecular data had been used.

Background Treatment of ESBL- and AmpC-producing Enterobacteriaceae bacteremia is often complicated by lack of appropriate antibiotics. We aimed to determine the predictors of mortality and impact of empirical antibiotics. Methods A retrospective observational study was performed on consecutive adult cases of ESBL and AmpC bacteremia at the Alfred Hospital from 2014 through April 2018. Results Among 110 patients with ESBL (88.2%) and AmpC (14.5%) bacteremia episodes, 96.4% had comorbidities such as hematological malignancy (30%). Approximately 45% were on immunosuppressive drugs, while 69% had recent antibiotic exposure. Over 84% of bacteremias were hospital acquired or healthcare associated. Urinary tract was the main source of infection (40%) with E. coli being the commonest organism (66.4%). The isolates were least resistant to gentamicin (21.8%), which was often appropriately used in empirical therapy. About 34% of patients presented with severe sepsis or shock. The 30-day mortality rate was 20% with no correlation with inappropriate empirical antibiotics (52%). There was no significant mortality difference between carbapenem use in empirical and definitive therapy. Respiratory source [OR 11.77, 95% CI 1.30–106.85; p = 0.03], severe sepsis or shock [OR 5.17, 95% CI 1.37–19.55; p = 0.02] and inappropriate definitive therapy [OR 27.93, 95%CI 3.69–211.35; p = 0.001] were independent predictors for mortality. Conclusion The choice and appropriateness of empirical therapy were not associated with mortality in ESBL and AmpC bacteremia. Prudent use of carbapenem is reasonable with gentamicin as alternative. Emphasis should be on prompt resuscitation in severe sepsis and early detection of ESBL and AmpC to facilitate appropriate switch to definitive therapy.

[Background] Pseudomonas aeruginosa is mostly a nosocomial pathogen affecting predisposed patients. However, community-onset bloodstream infections (CO-BSI) caused by this organism are not exceptional. [Objectives] To assess the predisposing factors for CO-BSI due to P. aeruginosa (CO-BSI-PA) and the impact in mortality of inappropriate empirical antimicrobial therapy. Data source] A systematic literature search was performed in the Medline, Embase, Cochrane Library, Scopus and Web of Science databases. [Study eligibility criteria and participants: Articles published between 1 January 2002 and 31 January 2018 reporting at least of 20 adult patients with CO-BSI due to P. aeruginosa were considered. [Intervention] Empiric antimicrobial therapy for CO-BSI-PA. [Methods] A systematic review and a meta-analysis were conducted for risk factors and to evaluate if inappropriate empiric antimicrobial therapy increased mortality in CO-BSI-PA using a Mantel-Haenszel effects model. [Results] Twelve studies assessing data of 1120 patients were included in the systematic review. Solid tumour (33.1%), haematologic malignancy (26.4%), neutropenia (31.7%) and previous antibiotic use (44.8%) were the most prevalent predisposing factors. Septic shock was present in 42.3% of cases, and 30-day crude mortality was 33.8%. Mortality in meta-analysis (four studies) was associated with septic shock at presentation (odds ratio, 22.31; 95% confidence interval, 3.52–141.35; p 0.001) and with inappropriate empiric antibiotic therapy (odds ratio, 1.83; 95% confidence interval, 1.12–2.98l p 0.02). [Conclusions] CO-BSI-PA mostly occurred in patients with predisposing factors and had a 30-day mortality comparable to hospital-acquired cases. Inappropriate empirical antibiotic therapy was associated with increased mortality. Appropriate identification of patients at risk for CO-BSI-PA is needed for empirical treatment decisions.

BackgroundSeven structurally related β-lactamase-producing plasmids have been characterized in penicillinase-producing Neisseria gonorrhoeae (PPNG) isolates. We characterized a variant (i.e. pJRD20, Canada type) of the Africa-type (pJD5) plasmid isolated from N. gonorrhoeae strain 8903.ObjectivesTo compare the DNA sequence of pJRD20 with that of pJD5 and pJD4 (Asia-type) and their TEM-1 β-lactamases.MethodsN. gonorrhoeae 8903 was identified as part of the Gonococcal Antimicrobial Surveillance Program in Canada. β-Lactamase production was assessed using nitrocefin. MICs were determined by agar dilution and Etest methods (CLSI). The DNA sequences of pJRD20, pJD5 and pJD4 were assembled and annotated. The structure of TEM-1 and its penicillin-binding properties were determined by in silico molecular modelling and docking. TEM-1 proteins were characterized by western blot, mass spectrometry and ampicillin hydrolysis assays.ResultsN. gonorrhoeae 8903 exhibited intermediate susceptibility to penicillin with slow β-lactamase activity (i.e. 35 min to hydrolyse nitrocefin). Except for a novel 6 bp deletion starting at the G of the ATG start codon of blaTEM-1, the DNA sequence of pJRD20 was identical to that of pJD5. The TEM-1 β-lactamase produced by pJRD20 is 24 kDa and hydrolyses ampicillin only after several hours.ConclusionsThis unusual PPNG isolate might have been characterized as a non-PPNG owing to its low MIC of penicillin and its very slow hydrolysis of nitrocefin. Given the unusual nature of its TEM-1 β-lactamase, laboratories might consider extending the duration of nitrocefin hydrolysis assays.

Methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage is a major risk factor for infection, namely among populations in the community with inherent prompting factors, such as the homeless. In Portugal, there are no data on S. aureus/MRSA nasal carriage among the homeless community. A total of 84 homeless individuals living in Lisbon (34 with no permanent address and 50 living in shelter) were nasally screened for S. aureus/ MRSA. All isolates were characterized to determine antimicrobial susceptibility and clonal type. A total of 43 (51.2%) S. aureus carriers were identified, including a single individual colonized with MRSA (1.2%). S. aureus carriage rate was higher among individuals with no permanent address (58.8% versus 46%), younger (45.7 ± 12.7 versus 52.5 ± 10.8 years), and with diagnosis of asthma (9% versus 0%). The single MRSA belonged to the EMRSA-15 clone (PFGE D, ST15-SCCmec IVh, and spa type t790). Almost half of the methicillin-susceptible S. aureus (MSSA) isolates (41.9%, n = 18) belonged to two major clones, ST398-t1451 (n = 13) and ST30-t399/t11980/t12808 associated with PFGE I (n = 5). A high proportion of isolates showed non-susceptibility to mupirocin (64%), erythromycin (45%), and fusidic acid (20%) and induced resistance to clindamycin (39%). None of the isolates harboured PVL. Our results suggest that the homeless population of Lisbon does not constitute a reservoir of MRSA in the community, but harbour the highly transmissible ST398-t1451 MSSA lineage.

Background For an effective antimicrobial treatment, it is crucial that antibiotics reach sufficient concentrations in plasma and tissue. Currently no data exist regarding moxifloxacin plasma concentrations and exposure levels in tissue under septic conditions. Objectives To determine the pharmacokinetics of moxifloxacin in plasma and interstitial space fluid over a prolonged period. Patients and methods Ten septic patients were treated with 400 mg of moxifloxacin once a day; on days 1, 3 and 5 of treatment plasma sampling and microdialysis in the subcutis and muscle of the upper thigh were performed to determine concentrations of moxifloxacin in different compartments. This trial was registered in the German Clinical Trials Register (DRKS, register number DRKS00012985). Results Mean unbound fraction of moxifloxacin in plasma was 85.5±3.4%. On day 1, Cmax in subcutis and muscle was 2.8±1.8 and 2.5±1.3 mg/L, respectively, AUC was 24.8±15.1 and 21.3±10.5 mg·h/L, respectively, and fAUC0–24/MIC was 100.9±62.9 and 86.5±38.3 h, respectively. Cmax for unbound moxifloxacin in plasma was 3.5±0.9 mg/L, AUC was 23.5±7.5 mg·h/L and fAUC0–24/MIC was 91.6±24.8 h. Key pharmacokinetic parameters on days 3 and 5 showed no significant differences. Clearance was higher than in healthy adults, but tissue concentrations were comparable, most likely due to a lower protein binding. Conclusions Surprisingly, the first dose already achieved exposure comparable to steady-state conditions. The approved daily dose of 400 mg was adequate in our patient population. Thus, it seems that in septic patients a loading dose on the first day of treatment with moxifloxacin is not required.

Background The combination of cefepime and zidebactam (WCK5222), a novel β-lactam enhancer, has demonstrated activity against a wide variety of Gram-negative pathogens and is currently under clinical evaluation. Objectives To examine the activity of cefepime/zidebactam against: (i) a contemporary collection of Gram-negative isolates from New York City; (ii) a collection of carbapenem-resistant clinical isolates; and (iii) a collection of isolates with characterized resistance mechanisms. Methods Susceptibility tests were performed using broth microdilution for cefepime, zidebactam and cefepime/zidebactam (1:1). Results More than 99% of a contemporary collection of Escherichia coli, Klebsiella pneumoniae and Enterobacter spp. had cefepime/zidebactam MICs ≤2 mg/L, the susceptibility breakpoint for cefepime. For K. pneumoniae, the acquisition of blaKPC resulted in increased MICs, although MICs remained ≤2 mg/L for 90% of KPC-possessing isolates. Overall for Pseudomonas aeruginosa, 98% of isolates had MICs ≤8 mg/L and MICs were affected by increased expression of ampC. For carbapenem-resistant P. aeruginosa, 78% of isolates had cefepime/zidebactam MICs ≤8 mg/L. The activity of cefepime/zidebactam against Acinetobacter baumannii was lower, with 85% of all isolates and 34% of carbapenem-resistant isolates with MICs ≤8 mg/L (cefepime interpretative criteria). Conclusions Cefepime/zidebactam demonstrated excellent activity against Enterobacteriaceae and P. aeruginosa, although activity was reduced in carbapenem-non-susceptible isolates. The activity against A. baumannii was reduced and studies examining the therapeutic efficacy in strains with high cefepime/zidebactam MICs are warranted.

Background Reduced ethambutol serum concentrations are commonly observed among TB patients co-infected with HIV and may lead to treatment failure. Objectives To perform a population pharmacokinetic study of ethambutol in HIV/TB patients, and to evaluate an intensified ethambutol weight-based dosing strategy to support pharmacokinetic target attainment. Methods We conducted a prospective study of ethambutol pharmacokinetics among HIV/TB patients administered first-line TB treatment in Botswana, with study visits before and after initiation of ART. Clinical and disease status markers, including HIV-associated systemic immune activation and gut dysfunction biomarkers, were evaluated as covariates of ethambutol pharmacokinetic parameters in non-linear mixed effects analysis. Monte Carlo simulations were performed to compare pharmacokinetic target attainment under standard and intensified weight-based ethambutol dosing strategies. Results We studied 40 HIV/TB patients prior to initiation of ART, of whom 24 returned for a second visit a median of 33 days following ART initiation. Ethambutol serum concentrations were best explained by a two-compartment model with first-order elimination, with a significant improvement in oral bioavailability following ART initiation. In Monte Carlo simulations, a supplementary ethambutol dose of 400 mg daily led to >2-fold improvements in pharmacokinetic target attainment probabilities in lung tissue, both before and after ART initiation. Conclusions Low serum ethambutol concentrations were commonly observed among HIV/TB patients in Botswana, and the oral bioavailability of ethambutol increased following ART initiation. Supplementary ethambutol dosing among HIV/TB patients may provide a strategy to optimize anti-TB treatment regimens in this high-risk population.