Zinc oxide nanoparticles and Klebsiella sp. SBP-8 alleviates chromium toxicity in Brassica juncea by regulation of antioxidant capacity, osmolyte production, nutritional content and reduction in chromium adsorption.

Heavy metals are one of the most damaging environmental toxins that hamper growth of plants. These noxious chemicals include lead (Pb), arsenic (As), nickel (Ni), cadmium (Cd) and chromium (Cr). Chromium is one of the toxic metal which induces various oxidative processes in plants. The emerging role of nanoparticles as pesticides, fertilizers and growth regulators have attracted the attention of various scientists. Current study was conducted to explore the potential of zinc oxide nanoparticles (ZnONPs) alone and in combination with plant growth promoting rhizobacteria (PGPR) Klebsiella sp. SBP-8 in Cr stress alleviation in Brassica juncea (L.). Chromium stress reduced shoot fresh weight (40%), root fresh weight (28%), shoot dry weight (28%) and root dry weight (34%) in B. juncea seedlings. Chromium stressed B. juncea plants showed enhanced levels of malondialdehyde (MDA), electrolyte leakage (EL), hydrogen peroxide (H2O2) and superoxide ion (O2• -). However, co-supplementation of ZnONPs and Klebsiella sp. SBP-8 escalated the activity of antioxidant enzymes i.e., superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) in B. juncea grown in normal and Cr-toxic soil. It is further proposed that combined treatment of ZnONPs and Klebsiella sp. SBP-8 may be useful for alleviation of other abiotic stresses in plants.

Correlation between antibiotic consumption and the occurrence of multidrug-resistant organisms in a Malaysian tertiary hospital: a 3-year observational study.

Inappropriate use of antibiotics has been shown to contribute to the occurrence of multidrug-resistant organisms (MROs). A surveillance study was performed in the largest tertiary care hospital in Kuala Lumpur, Malaysia, from 2018 to 2020 to observe the trends of broad-spectrum antibiotics (beta-lactam/beta-lactamases inhibitors (BL/BLI), extended-spectrum cephalosporins (ESC), and fluoroquinolones (FQ)) and antibiotics against MRO (carbapenems, polymyxins, and glycopeptides) usage and the correlation between antibiotic consumption and MROs. The correlation between 3-year trends of antibiotic consumption (defined daily dose (DDD)/100 admissions) with MRO infection cases (per 100 admissions) was determined using a Jonckheere-Terpstra test and a Pearson's Correlation coefficient. The antimicrobial resistance trend demonstrated a positive correlation between ESC and FQ towards the development of methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Klebsiella spp, ESBL-producing Escherichia coli (E. coli), and MRO Acinetobacter baumannii (A. baumannii). Increasing carbapenem consumption was positively correlated with the occurrence of ESBL-producing Klebsiella spp and E. coli. Polymyxin use was positively correlated with ESBL-producing Klebsiella spp, MRO A. baumannii, and carbapenem-resistant Enterobacteriaceae. The findings reinforced concerns regarding the association between MRO development, especially with a surge in ESC and FQ consumption. Stricter use of antimicrobials is thus crucial to minimise the risk of emerging resistant organisms.

Neonatal septicemia at intensive care unit, Ayder Comprehensive Specialized Hospital, Tigray, North Ethiopia: Bacteriological profile, drug susceptibility pattern, and associated factors.

BACKGROUND: Neonatal septicemia is a life threatening medical emergency that requires timely detection of pathogens with urgent rational antibiotics therapy. METHODS: A cross-sectional study was conducted between March 2017 to September 2018 among 317 septicemia suspected neonates at neonatal intensive care unit, Ayder Comprehensive Specialized Hospital, Mekelle, Tigray, North Ethiopia. A 3 mL of blood was collected from each participant. Identification of bacterial species was done using the standard microbiological techniques. Antibiotic sensitivity test was done using disk diffusion method. Data were entered and analyzed using computer software SPSS version 22. Bivariate and multivariate regression analysis was applied to determine the association between variables. RESULTS: Of the 317 (190 male and 127 female) neonates, 116 (36.6%) were found to be with culture proven septicemia. Klebsiella species were the predominant etiologic agents. Length of hospital stay (AOR (adjusted odds ratio) = 3.65 (2.17-6.13), p < 0.001) and low birth weight (AOR = 1.64 (1.13-2.78), p = 0.04) were the factors associated with neonatalsepticemia. Most isolates showeda frightening drug resistance rate to the commonly used antimicrobial drugs. K. pneumoniae, E. coli, Enterobacter and Citrobacter species were 57% to100% resistant to ceftazidime, ceftriaxone, gentamycin, amoxacillin-clavulunic acid and ampicillin. All, 9 (100%) isolates of S. aureus were resistant to oxacilline, ampicillin,erythromycin and gentamycin. Furthermore, 55.6% S. aureus isolates were Methicillin Resistant Staphylococcus aureus. CONCLUSION: Neonaltal septicemia is found to be significantly high in the present study. As most of the isolates are potentially related to hospital acquired infections, prevention and control policy should have to be more strengthening in the neonatal intensive care unit.

Characterization of Rosa canina Fruits Collected in Urban Areas of Slovakia. Genome Size, iPBS Profiles and Antioxidant and Antimicrobial Activities.

The studies of plant bacterial endophytes, colonizing the plant tissues without any signs of diseases, are essential for understanding of ecological interactions. The aim of our study is to detect microbiological contamination and to assess the antimicrobial, antioxidant activity, total phenolic, carotenoid content, genome size, and ploidy of non-cultivated Rosa canina sampled from urban areas. Samples of Rosa canina fruits were collected in three locations in Slovakia. The highest total viable count and the Enterobacteriaceae count in fruits were 4.32 log CFU/g and 4.29 log CFU/g, respectively. Counts of the mesophilic anaerobic sporulating bacteria, Pseudomonas spp., and of the microscopic fungi and yeasts were 3.00, 2.15 log CFU/g, 3.65 log CFU/g, and 2.76 log CFU/g, respectively. Regarding the antimicrobial activity, Escherichia coli and Klebsiela oxytoca were the most sensitive species among the assayed microorganisms to the treatment with the ethanolic extracts of Rosa canina fruits. The fruits were rich in bioactive compounds, polyphenols, and carotenoids, that could be related to their antioxidant activity. Genome sizes of analyzed samples ranged from 2.3 to 2.96. DNA-based fingerprinting obtained by iPBS markers of the Rosa canina var. lapidicola Heinr. Braun., was characterized by some distinctive inserted loci. An interdisciplinary study was performed for the dog roses from different parts of Slovakia that resulted in deeper characterization of this species.

Synergistic and antagonistic effects of Citrus bergamia distilled extract and its major components on drug resistant clinical isolates.

In this study we determine the in vitro antimicrobial activities of Citrus bergamia distilled extract and compounds isolated from such extract against clinical MDR strains. The activity of these substances were tested using a broth microdilution assay, their MBC and their FBC to evaluate the nature of the interactions in tested components. Among Gram negative bacteria Enterobacter spp, Klebsiella spp and Pseudomonas spp exhibited the higher MBC values range (2.5-5% v/v). Among Gram positive and Yeast isolates, Corynebacterium spp, Enterococcus faecalis and Staphylococcus spp, as well as Candida lipolytica and lusitanae showed a range of 2.5 to >5% of MBC. To overcome such resistance toward the distilled extract, were used combination of isolated compounds from the same extract. Klebsiella pneumoniae 16/15 and Pseudomonas aeruginosa 7/15 were sensitive to synergistic effect of some tested combinations. Broad spectrum of antimicrobial activity was demonstrated for C. bergamia components and their combinations.

Clinical pharmacokinetics of flomoxef in prostate tissue and dosing considerations for prostatitis based on site-specific pharmacodynamic target attainment.

Flomoxef is used to treat bacterial prostatitis; however, its prostatic pharmacokinetics have not been fully clarified. Flomoxef (500 or 1000 mg) was administered to patients with benign prostatic hypertrophy (n = 54). After a 0.5-h infusion, venous blood samples were drawn at time points of 0.5-5 h, and prostate tissue samples were collected at time points of 0.5-1.5 h during transurethral resection of the prostate. The drug concentrations in plasma and prostate tissue were analyzed pharmacokinetically and used for a stochastic simulation to predict the probability of attaining pharmacodynamic target in prostate tissue. Showing dose linearity in the prostatic pharmacokinetics, flomoxef rapidly penetrated into prostate tissue, with a prostate/plasma ratio of 0.48-0.50 (maximum drug concentration) and 0.42-0.55 (area under the drug concentration-time curve). Against the tested populations of Escherichia coli, Klebsiella and Proteus species isolates, 0.5-h infusion of 1000 mg three times daily achieved a ≥90% expected probability of attaining the bactericidal target (70% of the time above the minimum inhibitory concentration [MIC]) in prostate tissue. The site-specific pharmacodynamic-based breakpoint (the highest MIC at which the target-attainment probability in prostate tissue was >90%) values were 0.25 mg/L (MIC for 90th percentile of E. coli and Klebsiella species) for 500 mg four times daily and 0.5 mg/L (MIC90 of Proteus species) for 1000 mg four times daily. These results help to fully characterize the prostatic pharmacokinetics of flomoxef, while also helping to rationalize and optimize the dosing regimens for prostatitis based on site-specific pharmacodynamic target attainment.

Phytosynthesis of silver nanoparticles using Mangifera indica flower extract as bioreductant and their broad-spectrum antibacterial activity.

The present study focused on the evaluation of antibacterial property of silver nanoparticles (AgNPs) synthesized using mango flower extract. The morphology of the synthesized AgNPs was observed under transmission electron microscopy and the particles have shown spherical shape in the range of 10-20 nm. X-ray powder diffraction analysis confirmed the crystalline nature of the AgNPs. The atomic percentage of the Ag element in the nanoparticles was about 7.58% which is greater than the other elements present in the sample. The AgNPs showed extensive lethal effect on both Gram-positive (Staphylococcus sp.) and Gram-negative (Klebsiella sp., Pantoea agglomerans, and Rahnella sp.) bacteria. The extensive lethal effect of AgNPs against clinically important pathogens demonstrated that the mango flower mediated AgNPs could be applied as potential antibacterial agent to control the bacterial population in the respective industries.

Antibiotic combinations that exploit heteroresistance to multiple drugs effectively control infection.

Antibiotic-resistant bacteria are a significant threat to human health, with one estimate suggesting they will cause 10 million worldwide deaths per year by 2050, surpassing deaths due to cancer1. Because new antibiotic development can take a decade or longer, it is imperative to effectively use currently available drugs. Antibiotic combination therapy offers promise for treating highly resistant bacterial infections, but the factors governing the sporadic efficacy of such regimens have remained unclear. Dogma suggests that antibiotics ineffective as monotherapy can be effective in combination2. Here, using carbapenem-resistant Enterobacteriaceae (CRE) clinical isolates, we reveal the underlying basis for the majority of effective combinations to be heteroresistance. Heteroresistance is a poorly understood mechanism of resistance reported for different classes of antibiotics3-6 in which only a subset of cells are phenotypically resistant7. Within an isolate, the subpopulations resistant to different antibiotics were distinct, and over 88% of CRE isolates exhibited heteroresistance to multiple antibiotics ('multiple heteroresistance'). Combinations targeting multiple heteroresistance were efficacious, whereas those targeting homogenous resistance were ineffective. Two pan-resistant Klebsiella isolates were eradicated by combinations targeting multiple heteroresistance, highlighting a rational strategy to identify effective combinations that employs existing antibiotics and could be clinically implemented immediately.

Oral fosfomycin for the treatment of chronic bacterial prostatitis.

BACKGROUND: Chronic bacterial prostatitis (CBP) is a difficult-to-treat infection as only a few antibiotics achieve therapeutic concentrations in the prostate. Data on the efficacy and safety of oral fosfomycin for the treatment of CBP are limited. OBJECTIVES: To analyse the efficacy and safety of fosfomycin in CBP due to MDR pathogens. METHODS: In a prospective observational study, an oral regimen of 3 g of fosfomycin q24h for 1 week followed by 3 g q48h for a treatment duration of 6-12 weeks was administered. The outcome was clinical and microbiological cure rate at the end of treatment (EOT) and rate of relapse at 3 and 6 months. RESULTS: The study included 44 patients. The most common pathogen was Escherichia coli (66%), followed by Klebsiella spp. (14%) and Enterococcus faecalis (14%). Most strains were MDR (59%) and 23% had an ESBL phenotype; 33 of 44 strains were resistant to fluoroquinolones, but all were susceptible to fosfomycin (median MIC for Gram-negative pathogens 1.5 mg/L). In 25 patients, treatment was administered for 6 weeks, whereas in the remaining 19 patients it was prolonged to 12 weeks based on the presence of calcifications in the prostate. Cure rate was 82% at EOT and 80% and 73% at 3 and 6 months accordingly. Microbiological eradication was achieved in 86% and 77% at EOT and at 6 months, respectively. Failure was observed in 12 patients. The most common adverse event was diarrhoea (18%). CONCLUSIONS: Oral fosfomycin, particularly in the era of MDR prevalence, represents an attractive, safe and effective alternative to fluoroquinolones for the treatment of CBP.

Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular Activities through Drug Efflux Pump and Biofilm Inhibition.

Disulfides from Allium stipitatum, commonly known as Persian shallot, were previously reported to possess antibacterial properties. Analogues of these compounds, produced by S-methylthiolation of appropriate thiols using S-methyl methanethiosulfonate, exhibited antimicrobial activity, with one compound inhibiting the growth of Mycobacterium tuberculosis at 17 µM (4 mg L-1) and other compounds inhibiting Escherichia coli and multi-drug-resistant (MDR) Staphylococcus aureus at concentrations ranging between 32-138 µM (8-32 mg L-1). These compounds also displayed moderate inhibitory effects on Klebsiella and Proteus species. Whole-cell phenotypic bioassays such as the spot-culture growth inhibition assay (SPOTi), drug efflux inhibition, biofilm inhibition and cytotoxicity assays were used to evaluate these compounds. Of particular note was their ability to inhibit mycobacterial drug efflux and biofilm formation, while maintaining a high selectivity towards M. tuberculosis H37Rv. These results suggest that methyl disulfides are novel scaffolds which could lead to the development of new drugs against tuberculosis (TB).

Frequency and Antibiotic Resistance of Bacteria Implicated in Community Urinary Tract Infections in North Aveiro Between 2011 and 2014.

AIMS: The present study aims to evaluate the predominance of uropathogens responsible for urinary tract infection (UTI) and determine their resistance patterns, to assess if the recommended empirical treatment is appropriate for the studied population. Samples were collected in Aveiro (Portugal) from an ambulatory service between June 2011 and June 2014. RESULTS: From the 4,270 positive urine samples for UTI, 3,561 (83%) were from women and only 709 (17%) were from men. The bacterium Escherichia coli was the most frequent uropathogen, followed by Klebsiella sp., Enterococcus sp., and Proteus mirabilis. E. coli was also the uropathogen presenting less resistance to antibiotics, including those recommended as first and second line UTI treatment. In general, bacteria isolated from men were more resistant to antimicrobials than bacteria isolated from women. CONCLUSIONS: The results of this study emphasized the relevance to consider sex as a differentiating factor in the choice of UTI empirical treatment, mainly due to differences in antimicrobial resistance. From the first line drugs recommended by the European Association of Urology (EAU) to empirical treatment of uncomplicated UTI, nitrofurantoin is the most appropriate drug for both sexes. Ciprofloxacin, although appropriate for treatment in women, is not appropriate to treat UTIs in men. From the second line drugs, both trimethoprim-sulfamethoxazole (TMP-SMX) and amoxicillin-clavulanic acid (AMX-CA) are appropriate drugs for treatment of uncomplicated UTI in women, but not as effective for men.

Biomimetic synthesis of silver nanoparticles using flower extract of Bauhinia purpurea and its antibacterial activity against clinical pathogens.

In the present study, we have reported an eco-friendly, rapid, and simple method for the synthesis of silver nanoparticles (AgNPs) using Bauhinia purpurea flower extract as non-toxic bioreducing agent. The formation of AgNPs was confirmed by UV-visible spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy and energy-dispersive spectroscopy (SEM-EDS), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). The synthesized AgNPs were spherical in shape with an average size of 20 nm. Furthermore, the antibacterial activities of the synthesized AgNPs (2-10 mM) against clinical pathogens, Klebsiella sp. and Staphylococcus sp., were evaluated under in vitro conditions.

Association of high mortality with extended-spectrum ß-lactamase (ESBL) positive cultures in community acquired infections.

PURPOSE: Infections due to multidrug resistant organisms have become a serious health concern worldwide. The present study was conducted to investigate the spectrum of microbial resistance pattern in the community and their effects on mortality. METHODS: A retrospective review and analysis of prospectively collected data was done of all patients admitted with diagnosis of sepsis in two tertiary care ICU's for a period of two years. Demographics, culture positivity, microbial spectrum, resistance pattern and outcome data were collected. RESULTS: Out of 5309 patients enrolled; 3822 had suspected clinical infection on admission with 1452 patients growing positive microbial cultures. Among these, 201 bacterial strains were isolated from patients who had community acquired infections. 73% were Gram negative bacilli, commonest being E. coli (63%). 63.4% E. coli and 60.7% Klebsiella isolates were ESBL producers. The mortality in ESBL positive infections was significantly higher as compared to ESBL negative infections (Odds ratio 2.756). Moreover, ESBL positive patients empirically treated with Beta Lactams+Beta Lactamase inhibitors (BL+BLI) had significantly higher mortality as compared to patients treated with carbapenems. More data from multiple centres need to be gathered to formulate appropriate antibiotic policy for critically ill patients admitted from the community.

Efficacy ratio: A tool to enhance optimal antimicrobial use for intra-abdominal infections.

BACKGROUND: Antimicrobial resistance and inappropriate antibiotic regimen hamper a favorable outcome in intra-abdominal infections. Clinicians rely on the minimum inhibitory concentration (MIC) value to choose from the susceptible antimicrobials. However, the MIC values cannot be directly compared between the different antibiotics because their breakpoints are different. For that reason, efficacy ratio (ER), a ratio of susceptible MIC breakpoint and MIC of isolate, can be used to choose the most appropriate antimicrobial. MATERIALS AND METHODS: A prospective, observational study conducted during 2015 and 2016 included 356 Escherichia coli and 158 Klebsiella spp. isolates obtained from the intra-abdominal specimens. MIC was determined by microbroth dilution method, and ER of each antibiotic was calculated for all the isolates. RESULTS: For both E. coli and Klebsiella spp., ertapenem, amikacin, and piperacillin/tazobactam had the best activities among their respective antibiotic classes. DISCUSSION: This is the first study calculating ER for deciding empiric treatment choices. ER also has a potential additional value in choosing the use of susceptible drugs as monotherapy or combination therapy. A shift in ERs over a period of time tracks rising MIC values and predicts antimicrobial resistance development. CONCLUSION: Estimation of ER could be a meaningful addition for the interpretation of an antimicrobial susceptibility report, thus helping the physician to choose the best among susceptible antimicrobials for patient management.

Extraction, isolation and characterization of bioactive compounds from chloroform extract of Carica papaya seed and it's in vivo antibacterial potentiality in Channa punctatus against Klebsiella PKBSG14.

The relative efficacy of the isolated pure compound, extracted from Carica papaya seed has been tested against live fish, Channa punctatus infected with pathogenic strains of KlebsiellaPKBSG14 (gene bank accession no.KJ162158) at a dose of 0.75 CFU/ml in vivo. The isolated compound has been characterized by chromatography and mass spectroscopy studies using FTIR, 1HNMR and 13c NMR to identify as well as to determine the nature of the pure compound. This study revealed the extracted biological molecule is oleic acid, a long chained saturated fatty acid (LFAs) with a molecular formula C18H34O2. Later this compound was analyzed for its efficacy as an antibacterial agent in vivo through cytotoxicological and genotoxicological assays. A dose of 0.5 mg/kg and 1 mg/kg b.w of isolated pure oleic acid has been tested and it showed effective result in regard to DNA fragmentation, comet tail length and toxicity biomarkers like ROS generation. The results of in vivo studies showed similar effects on spleen cells with regard to cell viability by PI staining, cell cycle analysis and also Annexin-FITC assay. Thus, the overall results suggest that oleic acid increases drug bioavailability and thereby has a better chemo-preventive action against bacterial infection in vivo.

Biosynthesis of silver nanoparticles from Spirulina microalgae and its antibacterial activity.

The present work focuses on a low-cost, simple, and green synthesis of silver nanoparticles (AgNPs) by mixing AgNO3 solution with the extract of Spirulina platensis (SP) without any chemical reducing and/or capping agents. The green synthesis of AgNPs was confirmed by the color change from colorless to yellowish brown. The biosynthesis of AgNPs was further confirmed by UV-visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), biological transmission electron microscopy (Bio-TEM), and energy dispersive X-ray analysis (EDX). The UV-vis spectroscopy results showed the surface plasmon resonance (SPR) of AgNPs around 450 nm. Bio-TEM analysis revealed that the Ag nanoparticles were well dispersed with average range of 5-50 nm. XRD results indicated that the green synthetic process produced face-centered cubic structure of AgNPs. FT-IR spectroscopy analysis showed that the bioactive molecules from the SP extract believed to be the responsible for the reduction of Ag ions. Furthermore, the synthesized AgNPs were evaluated against pathogens such as Staphylococcus sp. and Klebsiella sp. The AgNPs (1-4 mM) extensively reduced the growth rate of the pathogens.

Pharmacodynamic Evaluation of Fosfomycin against Escherichia coli and Klebsiella spp. from Urinary Tract Infections and the Influence of pH on Fosfomycin Activities.

Fosfomycin is widely used for the treatment of uncomplicated urinary tract infection (UTI), and it has recently been recommended that fosfomycin be used to treat infections caused by multidrug-resistant (MDR) Gram-negative bacilli. Whether urine acidification can improve bacterial susceptibility to fosfomycin oral dosing regimens has not been analyzed. The MIC of fosfomycin for 245 Gram-negative bacterial isolates, consisting of 158 Escherichia coli isolates and 87 Klebsiella isolates which were collected from patients with urinary tract infections, were determined at pH 6.0 and 7.0 using the agar dilution method. Monte Carlo simulation of the urinary fosfomycin area under the concentration-time curve (AUC) after a single oral dose of 3,000 mg fosfomycin and the MIC distribution were used to determine the probability of target attainment (PTA). Fosfomycin was effective against E. coli (MIC90 ≤ 16 µg/ml) but not against Klebsiella spp. (MIC90 > 512 µg/ml). Acidification of the environment increased the susceptibility of 71% of the bacterial isolates and resulted in a statistically significant decrease in bacterial survival. The use of a regimen consisting of a single oral dose of fosfomycin against an E. coli isolate with an MIC of ≤64 mg/liter was able to achieve a PTA of ≥90% for a target pharmacodynamic index (AUC/MIC) of 23 in urine; PTA was not achieved when the MIC was higher than 64 mg/liter. The cumulative fractions of the bacterial responses (CFR) were 99% and 55% against E. coli and Klebsiella spp., respectively, based on simulated drug exposure in urine with an acidic pH of 6.0. A decrease of the pH from 7.0 to 6.0 improved the PTA and CFR of the target pharmacodynamic index in both E. coli and Klebsiella isolates.

Patterns of antimicrobial resistance in intensive care unit patients: a study in Vietnam.

BACKGROUND: Antimicrobial resistance has emerged as a major concern in developing countries. The present study sought to define the pattern of antimicrobial resistance in ICU patients with ventilator-associated pneumonia. METHODS: Between November 2014 and September 2015, we enrolled 220 patients (average age ~ 71 yr) who were admitted to ICU in a major tertiary hospital in Ho Chi Minh City, Vietnam. Data concerning demographic characteristics and clinical history were collected from each patient. The Bauer-Kirby disk diffusion method was used to detect the antimicrobial susceptibility. RESULTS: Antimicrobial resistance was commonly found in ceftriaxone (88%), ceftazidime (80%), ciprofloxacin (77%), cefepime (75%), levofloxacin (72%). Overall, the rate of antimicrobial resistance to any drug was 93% (n = 153/164), with the majority (87%) being resistant to at least 2 drugs. The three commonly isolated microorganisms were Acinetobacter (n = 75), Klebsiella (n = 39), and Pseudomonas aeruginosa (n = 29). Acinetobacter baumannii were virtually resistant to ceftazidime, ceftriaxone, piperacilin, imipenem, meropenem, ertapenem, ciprofloxacin and levofloxacin. High rates (>70%) of ceftriaxone and ceftazidime-resistant Klebsiella were also observed. CONCLUSION: These data indicated that critically ill patients on ventilator in Vietnam were at disturbingly high risk of antimicrobial resistance. The data also imply that these Acinetobacter, Klebsiella, and Pseudomonas aeruginosa and multidrug resistance pose serious therapeutic problems in ICU patients. A concerted and systematic effort is required to rapidly identify high risk patients and to reduce the burden of antimicrobial resistance in developing countries.

Antimicrobial Activity of Ceftazidime-Avibactam against Gram-Negative Bacteria Isolated from Patients Hospitalized with Pneumonia in U.S. Medical Centers, 2011 to 2015.

Bacterial isolates were collected from patients hospitalized with pneumonia (PHP), including ventilator-associated pneumonia (VAP), from 76 U.S. medical centers in 2011 to 2015. The Gram-negative organisms (n = 11,185, including 1,097 from VAP) were tested for susceptibility to ceftazidime-avibactam and comparators by the broth microdilution method. ß-Lactamase-encoding genes were screened using a microarray-based assay on selected isolates. Pseudomonas aeruginosa and Klebsiella spp. were the most common Gram-negative bacteria isolated from PHP and VAP. Ceftazidime-avibactam was very active against P. aeruginosa (n = 3,402; MIC50/MIC90, 2 and 4 µg/ml; 96.6% susceptible), including isolates nonsusceptible to meropenem (86.3% susceptible to ceftazidime-avibactam), piperacillin-tazobactam (85.6% susceptible), or ceftazidime (80.6% susceptible). Ceftazidime-avibactam was also highly active against Enterobacteriaceae (MIC50/MIC90, 0.12 and 0.5 µg/ml; 99.9% susceptible), including carbapenem-resistant Enterobacteriaceae (CRE) (n = 189; MIC50/MIC90, 0.5 and 2 µg/ml; 98.0% susceptible) and multidrug-resistant (MDR) (n = 674; MIC50/MIC90, 0.25 and 1 µg/ml; 98.8% susceptible) and extensively drug-resistant (XDR) (n = 156; MIC50/MIC90, 0.5 and 2 µg/ml; 98.1% susceptible) Enterobacteriaceae isolates, as well as Klebsiella species isolates showing an extended-spectrum ß-lactamase (ESBL) screening-positive phenotype (n = 433; MIC50/MIC90, 0.25 and 1 µg/ml; 99.5% susceptible). Among Enterobacter spp. (24.8% ceftazidime nonsusceptible), 99.8% of the isolates, including 99.4% of ceftazidime-nonsusceptible isolates, were susceptible to ceftazidime-avibactam. The most common ß-lactamases detected among Klebsiella pneumoniae and E. coli isolates were K. pneumoniae carbapenemase (KPC)-like and CTX-M-15, respectively. Only 8 of 6,209 Enterobacteriaceae isolates (0.1%) were ceftazidime-avibactam nonsusceptible, three NDM-1-producing strains with ceftazidime-avibactam MIC values of >32 µg/ml and five isolates with ceftazidime-avibactam MIC values of 16 µg/ml and negative results for all ß-lactamases tested. Susceptibility rates among isolates from VAP were generally similar or slightly higher than those from all PHP.

Oral fosfomycin for treatment of urinary tract infection: a retrospective cohort study.

BACKGROUND: Fosfomycin is increasingly called upon for the treatment of multi drug-resistant (MDR) organisms causing urinary tract infection (UTI). We reviewed oral fosfomycin use for UTI treatment in a large UK hospital. The primary goal was to audit our clinical practice against current national guidelines. Secondary aims were to identify factors associated with treatment failure, and to investigate the potential for using fosfomycin in patients with co-morbidities. METHODS: We retrospectively studied 75 adult patients with UTI who received 151 episodes of treatment with fosfomycin from March 2013 to June 2015. We collected clinical data from our electronic patient record, and microbiology data pre- and post- fosfomycin treatment. We recorded additional data for patients receiving prolonged courses in order to make a preliminary assessment of safety and efficacy. We also reviewed >18,000 urinary tract isolates of Escherichia coli and Klebsiella spp. processed by our laboratory over the final year of our study period to determine the prevalence of fosfomycin resistance. RESULTS: There was a significant increase in fosfomycin treatment episodes over the course of the study period. Co-morbidities were present in 71 % of patients. The majority had E. coli infection (69 %), of which 59 % were extended spectrum beta-lactamase (ESBL)-producers. Klebsiella infections were more likely than E. coli to fail treatment, and more likely to be reported as fosfomycin resistant in cases of relapse following treatment. There were no adverse events in five patients treated with prolonged fosfomycin. Among all urinary isolates collected over a year, fosfomycin resistance was documented in 1 % of E. coli vs. 19 % of Klebsiella spp. (p < 0.0001). CONCLUSIONS: We report an important role for oral fosfomycin for MDR UTI treatment in a UK hospital population, and based on the findings from this study, we present our own local guidelines for its use. We present preliminary data suggesting that fosfomycin is safe and effective for use in patients with complex comorbidities and over prolonged time periods, but may be less effective against Klebsiella than E. coli.