First-line Antimicrobial Agents Research Articles

Rhodomyrtone: a new anti-Staphylococcus aureus agent against resistant strains.

Rhodomyrtone is a novel plant-derived antibiotic compound originally isolated from Rhodomyrtus tomentosa leaf extract. To evaluate the activity of rhodomyrtone against a group of MRSA strains, including isolates with reduced susceptibility or resistance to vancomycin, daptomycin, linezolid and ceftaroline. Broth microdilution testing was used to determine the MICs and MBCs of rhodomyrtone, fosfomycin, vancomycin, daptomycin, linezolid and ceftaroline. ROM had an MIC90 of 1 mg/L against 110 strains of MRSA from blood isolates as well as for all other isolates that were daptomycin resistant, VISA, VRSA or LRSA. The MBC90 were 4 mg/L across all groups tested. Among all S. aureus groups tested the ROM MBC did not exceed 8 mg/L. Rhodomyrtone demonstrated excellent activity against MRSA as well as isolates with resistance or reduced activity to other anti-MRSA drugs including vancomycin, daptomycin and linezolid. Rhodomyrtone may have potential clinical utility when treating patients with infections caused by MRSA including those with reduced susceptibility to first-line anti-MRSA antimicrobial agents.

Odontogenic infections in the antibiotic era: approach to diagnosis, management, and prevention.

The prevalence of odontogenic infections remains one of the highest in the world. If untreated, odontogenic infections can break through the limitation, disseminate to other organs or spaces, and cause high mortality rates. However, it is still difficult to rapidly target limited or disseminated infections in clinical practice. The type of disseminated odontogenic infections and the responsible bacteria have not been described in detail. Search databases (e.g., PubMed, MEDLINE, Web of Science, Embase) for reports published from 2018.1 to 2022.9. Use search strategies: ("odontogenic infections" OR "pulpitis" OR "periapical lesions" OR "periodontal diseases") AND ("disseminated infections" OR "complication"). Fourteen different types of disseminated odontogenic infections, most of which are polymicrobial infections, can spread through the body either direct or through hematogenous diffusion. Multiple microbial infections can be more invasive in the transmission of infection. Secondary infections are commonly associated with bacteria like Fusobacterium spp., Streptococcus spp., Peptostreptococcus spp., Prevotella spp., and Staphylococcus spp. Antibiotics with broad-spectrum activity are fundamental as first-line antimicrobial agents based on the microorganisms isolated from disseminated infections. This review elaborates on the epidemiology, microorganisms, risk factors, and dissemination routes, and provides evidence-based opinions on the diagnosis, multidisciplinary management, and prevention of odontogenic infections for dentists and clinicians.

Angiopep-2 Modified Exosomes Load Rifampicin with Potential for Treating Central Nervous System Tuberculosis

Central nervous system tuberculosis (CNS-TB) is the most devastating form of extrapulmonary tuberculosis. Rifampin (RIF) is a first-line antimicrobial agent with potent bactericidal action. Nonetheless, the blood-brain barrier (BBB) limits the therapeutic effects on CNS-TB. Exosomes, however, can facilitate drug movements across the BBB. In addition, exosomes show high biocompatibility and drug-loading capacity. They can also be modified to increase drug delivery efficacy. In this study, we loaded RIF into exosomes and modified the exosomes with a brain-targeting peptide to improve BBB permeability of RIF; we named these exosomes ANG-Exo-RIF. Exosomes were isolated from the culture medium of BMSCs by differential ultracentrifugation and loaded RIF by electroporation and modified ANG by chemical reaction. To characterize ANG-Exo-RIF, Western blot (WB), nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were performed. Bend.3 cells were incubated with DiI labeled ANG-Exo-RIF and then fluorescent microscopy and flow cytometry were used to evaluate the targeting ability of ANG-Exo-RIF in vitro. Fluorescence imaging and frozen section were used to evaluate the targeting ability of ANG-Exo-RIF in vivo. MIC and MBC were determined through microplate alamar blue assay (MABA). A novel exosome-based nanoparticle was developed. Compared with untargeted exosomes, the targeted exosomes exhibited high targeting capacity and permeability in vitro and in vivo. The MIC and MBC of ANG-Exo-RIF were 0.25 μg/mL, which were sufficient to meet the clinical needs. In summary, excellent targeting ability, high antitubercular activity and biocompatibility endow ANG-Exo-RIF with potential for use in future translation-aimed research and provide hope for an effective CNS-TB treatment.

Reagentless Sensing of Vancomycin Using an Indium Tin Oxide Electrode Grafted with Molecularly Imprinted Polymer including Ferrocenyl Group.

Vancomycin (VCM) is a first-line antimicrobial agent against methicillin-resistant Staphylococcus aureus, a cause of nosocomial infections. Therapeutic drug monitoring is strongly recommended for VCM-based chemotherapy. The authors attempted to develop a simple VCM sensor based on molecularly imprinted polymer (MIP), which can be used with simple operations. Methacrylic acid (MAA), acrylamide, methylenebisacrylamide, and allylamine carboxypropionate-3-ferrocene (ACPF) were copolymerized in the presence of VCM and grafted from the surface of indium-tin oxide (ITO) to obtain MIP-coated electrodes. The MIP-grafted ITO electrode was used for differential pulse voltammetry (DPV) measurements in a buffer solution containing VCM or whole bovine blood. The obtained current depends on the VCM concentration with high linearity. The dynamic range covered the therapeutic range (20–40 μg/mL) of the VCM but was almost insensitive to teicoplanin, which has a similar structure to VCM. The ITO electrodes grafted by the same procedure except for omitting either VCM or APCF were not sensitive to VCM. The sensitivity of the MIP electrodes to VCM in whole blood and buffered saline, but the background current in blood was higher than that in saline. This high background current was also seen in the deproteinized plasma. Thus, the current is probably originated from the oxidation of low molecular weight reducing agents in the blood. The MIP-grafted ITO electrode using ACPF as a functional monomer would be a promising highly selective sensor for real-time monitoring of VCM with proper correction of the background current.

Influence of Antimicrobial Stewardship and Molecular Rapid Diagnostic Tests on Antimicrobial Prescribing for Extended-Spectrum Beta-Lactamase- and Carbapenemase-Producing Escherichia coli and Klebsiella pneumoniae in Bloodstream Infection.

ABSTRACTThe objective of this study was to evaluate whether the addition of the Verigene BC-GN molecular rapid diagnostic test to standard antimicrobial stewardship practices (mRDT + ASP) decreased the time to optimal and effective antimicrobial therapy for patients with extended-spectrum beta-lactamase (ESBL)- and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae bloodstream infections (BSI) compared to conventional microbiological methods with ASP (CONV + ASP). This was a multicenter, retrospective cohort study evaluating the time to optimal antimicrobial therapy in 5 years of patients with E. coli or K. pneumoniae BSI determined to be ESBL- or carbapenemase-producing by mRDT and/or CONV. Of the 378 patients included (mRDT + ASP, n = 164; CONV + ASP, n = 214), 339 received optimal antimicrobial therapy (mRDT + ASP, n = 161; CONV + ASP, n = 178), and 360 (mRDT + ASP, n = 163; CONV + ASP, n = 197) received effective antimicrobial therapy. The mRDT + ASP demonstrated a statistically significant decrease in the time to optimal antimicrobial therapy (20.5 h [interquartile range (IQR), 17.0 to 42.2 h] versus 50.1 h [IQR, 27.6 to 77.9 h]; P < 0.001) and the time to effective antimicrobial therapy (15.9 h [IQR, 1.9 to 25.7 h] versus 28.0 h [IQR, 9.5 to 56.7 h]; P < 0.001) compared to CONV + ASP, respectively.IMPORTANCE Our study supports the additional benefit of molecular rapid diagnostic test in combination with timely antimicrobial stewardship program (ASP) intervention on shortening the time to both optimal and effective antimicrobial therapy in patients with ESBL- or carbapenemase-producing Escherichia coli and Klebsiella pneumoniae bloodstream infections, compared to conventional microbiological methods and ASP. Gram-negative infections are associated with significant morbidity and mortality, often resulting in life-threatening organ dysfunction. Both resistance phenotypes confer resistance to many of our first-line antimicrobial agents with carbapenemase-producing Enterobacterales requiring novel beta-lactam and beta-lactamase inhibitor combinations or other susceptible non-beta-lactam antibiotics for treatment. National resistance trends in a cohort of hospitalized patients at U.S. hospitals during our study period demonstrate the increasing incidence of both resistance phenotypes, reinforcing the generalizability and timeliness of such analysis.

Insects, Rodents, and Pets as Reservoirs, Vectors, and Sentinels of Antimicrobial Resistance.

This paper reviews the occurrence of antimicrobial resistance (AMR) in insects, rodents, and pets. Insects (e.g., houseflies, cockroaches), rodents (rats, mice), and pets (dogs, cats) act as reservoirs of AMR for first-line and last-resort antimicrobial agents. AMR proliferates in insects, rodents, and pets, and their skin and gut systems. Subsequently, insects, rodents, and pets act as vectors that disseminate AMR to humans via direct contact, human food contamination, and horizontal gene transfer. Thus, insects, rodents, and pets might act as sentinels or bioindicators of AMR. Human health risks are discussed, including those unique to low-income countries. Current evidence on human health risks is largely inferential and based on qualitative data, but comprehensive statistics based on quantitative microbial risk assessment (QMRA) are still lacking. Hence, tracing human health risks of AMR to insects, rodents, and pets, remains a challenge. To safeguard human health, mitigation measures are proposed, based on the one-health approach. Future research should include human health risk analysis using QMRA, and the application of in-silico techniques, genomics, network analysis, and ’big data’ analytical tools to understand the role of household insects, rodents, and pets in the persistence, circulation, and health risks of AMR.

The Impact of Cefazolin Shortage on Surgical Site Infection Following Spine Surgery in Japan.

Retrospective study using prospectively collected data. This study aimed to investigate the effect of alternative antimicrobial prophylaxis agents on surgical site infections (SSIs) after spine surgery. Although the use of alternative antimicrobial prophylaxis agents might have a negative effect on SSI prevention, their association with SSI risk in spine surgery remains unclear. We used the registry data of consecutive patients undergoing spine surgery from April 2017 to January 2020 in four institutions participating in the University of Tokyo Spine Group. Before March 2019, all institutions used cefazolin for antimicrobial prophylaxis. After March 2019, the institutions used broad-spectrum beta-lactam agents as an alternative due to a cefazolin shortage in Japan. Among the 3841 enrolled patients (2289 males), 2024 received cefazolin and 1117 received alternative agents. The risk of reoperation for deep SSI within 30 days of spine surgery was significantly higher in the alternative antimicrobial prophylaxis agent group (adjusted odds ratio [aOR] 1.96; 95% confidence interval [CI], 1.15-3.35; P = 0.014). In subgroup analyses, the SSI risk was significantly higher in the thoracolumbar surgery group (aOR 1.98; 95% CI, 1.06-3.73; P = 0.03). A nonsignificant consistent trend was found in all other subgroups: posterior decompression (aOR 1.91; 95% CI, 0.86-4.21; P = 0.11); posterior fixation (aOR 2.05; 95% CI, 0.99-4.24; P = 0.05); and cervical spine surgery (aOR 2.30; 95% CI, 0.82-6.46; P = 0.11). Alternative antimicrobial prophylaxis agents increased the risk of reoperation for SSI after spine surgery compared with cefazolin. Our study supports the current practice of using first-generation cephalosporins as first-line antimicrobial prophylaxis agents in spine surgery as recommended in multiple guidelines.Level of Evidence: 3.

Susceptibility of hospital-acquired uropathogens to first-line antimicrobial agents at a tertiary health-care hospital, Saudi Arabia.

Context:Management of urinary tract infections (UTIs) is caused by antibiotic resistance uropathogens.Aim:This study aimed to determine the important uropathogens and their resistance to first-line urinary tract antimicrobial agents.Settings and Design:The region of Aseer, Southern Saudi Arabia, between 2013 and 2016.Materials and Methods:A total of 1506 isolates were recovered from the urine samples of patients that were identified and tested against nine first-line UTI antimicrobial agents. Laboratory analysis was done as per the standard methods. Confirmation of bacterial identity and antimicrobial susceptibility assay was achieved by the VITEK 2 automated system.Statistical Analysis Used:Statistical Package for the Social Sciences software version 21.0 was used for the statistical analysis.Results:The dominant uropathogens were Escherichia coli (E. coli) 507 (33.7%); Klebsiella pneumoniae (K. pneumoniae), 229 (15.21%); Pseudomonas aeruginosa, 153 (10.2%); Acinetobacter baumannii, 80 (5.3%); Enterococcus faecalis, 71 (4.7%); and Proteus mirabilis, 61 (4.1%). Of all culture-positive uropathogens, 51.5% were resistant to the 39 agents, whereas 48.5% were sensitive (P = 0.7969). Regarding the susceptibility to the first-line agent, the most effective against the dominant (in vitro) agents against E. coli were fosfomycin and nitrofurantoin (93.5%) and (85.4%), respectively. Whereas those worked well against K. pneumoniae were cefoxitin (57.1).Conclusions:The present study recommends the use of fosfomycin, cefoxitin, nitrofurantoin, and amoxicillin/clavulanate as the first choice UTIs treatment given their relatively high in vitro activity against major uropathogens. Knowledge of the bacterial species and their antimicrobial sensitivity patterns are always necessary to serve as a base for selecting the empirical treatment of UTIs as resistance rates vary geographically and with time.

Antimicrobial susceptibility surveillance of bacterial isolates recovered in Japan from odontogenic infections in 2013

We report on the findings of the first antimicrobial susceptibility surveillance study in Japan of isolates recovered from odontogenic infections. Of the 38 facilities where patients representing the 4 groups of odontogenic infections were seen, 102 samples were collected from cases of periodontitis (group 1), 6 samples from pericoronitis (group 2), 84 samples from jaw inflammation (group 3) and 54 samples from phlegmon of the jaw bone area (group 4) for a total of 246 samples. The positivity rates of bacterial growth on culture were 85.3%, 100%, 84% and 88.9%, respectively, for groups 1, 2, 3 and 4. Streptococcus spp. isolation rates according to odontogenic infection group were 22% (group 1), 17.7% (group 3) and 20.7% (group 4). Anaerobic isolation rates were 66.9% (group 1), 71.8% (group 3) and 68.2% (group 4). Drug susceptibility tests were performed on 726 strains excluding 121 strains that were undergrown. The breakdown of the strains subjected to testing was 186 Streptococcus spp., 179 anaerobic gram-positive cocci, 246 Prevotella spp., 27 Porphyromonas spp., and 88 Fusobacterium spp. The isolates were tested against 30 antimicrobial agents.Sensitivities to penicillins and cephems were good except for Prevotella spp. The low sensitivities of Prevotella spp is due to β-lactamase production. Prevotella strains resistant to macrolides, quinolones, and clindamycin were found. No strains resistant to carbapenems or penems were found among all strains tested. No anaerobic bacterial strain was resistant to metronidazole.Antimicrobial susceptibility testing performed on the S. anginosus group and anaerobic bacteria, which are the major pathogens associated with odontogenic infections, showed low MIC90 values to the penicillins which are the first-line antimicrobial agents for odontogenic infections; however, for Prevotella spp., penicillins combined with β-lactamase inhibitor showed low MIC90 values.

Resistance to multiple first-line antibiotics among Escherichia coli from poultry in Western Algeria.

Background and Aim:Escherichia coli can cause a number of serious infections both in human and veterinary medicine. Their management is increasingly complicated by the emergence and dissemination of multiresistance to various first-line antimicrobial agents. This study aimed to evaluate the resistance level to the commonly used antibiotics, with a focus on the first-line antimicrobial agents, in E. coli strains isolated from poultry in Western Algeria.Materials and Methods:E. coli culture was done on MacConkey agar and their identification was determined by AP20E system. For susceptibility testing, disk diffusion method to 14 antimicrobials, including first-line antibiotics, was used according to Kirby–Bauer disk diffusion method in Mueller-Hinton agar and the results were interpreted according to the Clinical and Laboratory Standards Institute guidelines. E. coli isolates were considered as multidrug resistance (MDR) when found resistant to at least one antimicrobial agent of three different families of antibiotics. Double-disk synergy and combination disk tests were used for initial screening and confirmation for extended-spectrum β-lactamases (ESBLs) production, respectively.Results:A total of 145 E. coli strains were isolated in this study. High resistance levels to various antibiotics, including commonly used first-line antimicrobial agents, were recorded in this study. The highest resistance level was observed against nalidixic acid (90.34%, n=131), followed by tetracycline (86.89%, n=126), ampicillin (82.75%, n=120), enrofloxacin (80.68%, n=117) and neomycin (80.68%, n=117), trimethoprim/sulfamethoxazole (73.79%, n=107), norfloxacin (72.41%, n=105) and cephalothin (72.41%, n=105), amoxicillin/clavulanic acid (51.72%, n=75), chloramphenicol (22.75%, n=33), nitrofurantoin (17.24%, n=25), gentamicin (13.10%, n=19), and ceftiofur (3.44%, n=5). Moreover, resistance to multiple first-line antibiotics was also demonstrated in the present study. Overall, 139 out of 145 isolates (95.86%) demonstrated MDR (resistant to at least three antibiotics). In addition, five E. coli isolates (3.44%) were confirmed to be ESBL producers.Conclusion:The alarming rate of E. coli resistant to multiple first-line antibiotics in poultry demands intensified surveillance. These results call for taking drastic measures to preserve antibiotic effectiveness and reduce the emergence risks of extensively drug-resistant and pandrug-resistant E. coli isolates.

Urinary tract infection and subclinical bacteriuria in cats: A clinical update.

Practical relevance:Urinary tract infection (UTI) is an important cause of feline lower urinary tract disease (FLUTD), particularly in female cats older than 10 years of age. In addition to cats with typical clinical signs of FLUTD or upper UTI, many cats have subclinical bacteriuria, but the clinical relevance of this is currently uncertain. UTIs are one of the most important indications for antimicrobial use in veterinary medicine and contribute to the development of antimicrobial resistance. Adherence to treatment guidelines and confinement to a few first-line antimicrobial agents is imperative to avoid further deterioration of the antimicrobial resistance situation. The decision to treat with antimicrobials should be based on the presence of clinical signs, and/or concurrent diseases, and the results of urine culture and susceptibility testing.Clinical challenges:Distinguishing between cats with bacterial cystitis, and those with idiopathic cystitis and concurrent clinical or subclinical bacteriuria, is challenging, as clinical signs and urinalysis results may be identical. Optimal treatment of subclinical bacteriuria requires clarification as there is currently no evidence that demonstrates a beneficial effect of routine treatment. Management of recurrent UTIs remains a challenge as evidence for most alternatives used for prevention in cats is mainly anecdotal, and no preventive treatment modality is currently recommended.Evidence base:This review draws on an extensive literature base in veterinary and human medicine, including the recently updated guidelines of the International Society for Companion Animal Infectious Diseases for the diagnosis and management of bacterial urinary tract infections in dogs and cats. Where published evidence is lacking, the authors describe their own approach; notably, for the bacteriuric cat with chronic kidney disease.

Drug resistance and clarithromycin resistance gene mutations in Helicobacter pylori strains circulating in Changchun area

Objective To investigate the resistance of Helicobacter pylori (H.pylori) strains to common antibiotics and to analyze the sites of genetic mutations carried by clarithromycin-resistant strains in order to provide reference for selecting sensitive antibiotics against H. pylori and for providing individualized treatment for patients in Changchun area. Methods Drug resistance of H. pylori clinical isolates to common antibiotics was detected by disk dilution method. The 23S rRNA genes of clarithromycin-resistant strains were amplified by PCR and then sequenced to analyze the presence of mutations. Results In this study, 69 strains of H. pylori were successfully isolated with a positive rate of 23.1%. Results of the drug susceptibility test to seven commonly used antibiotics showed that there were 52.2% of the isolates resistant to clarithromycin, 47.8% to tinidazole, 37.7% to levofloxacin, 33.3% to tetracycline hydrochloride, 30.4% to furazolidone, 30.4% to metronidazole and 5.8% to amoxicillin. Amoxicillin could continue to be used as a first-line antimicrobial agent. Seven mutation sites were found in the 23S rRNA genes carried by the clarithromycin-resistant strains, which were A1821G, G1826A, T1830C, G1940A, A2143G, T2182C and A2223G. The A2143G site mutation accounted for 54.2% and was the predominant mutation resulting in the resistance to clarithromycin of H. pylori strains circulating in this area. Conclusions The H. pylori strains isolated from patients with gastroduodenal diseases in Changchun area had a high resistance rate to clarithromycin, which was mainly caused by the A2143G mutation in 23S rRNA gene. Key words: Helicobacter pylori; Clarithromycin resistance; 23S rRNA; Gene mutation

Detection of multidrug resistant Escherichia coli in the ovaries of healthy broiler breeders with emphasis on extended-spectrum β-lactamases producers

In the last few years, antimicrobial resistant (AMR) Escherichia coli have been detected in newborn chickens suggesting their vertical transmission from breeding birds to their offspring. However, little is known about the presence of AMR E. coli in the reproductive organs of broiler breeders. The aim of this study was to investigate the presence of E. coli in the ovaries of healthy broiler breeders and to study their antimicrobial resistance. Samples from broiler breeders (n = 80) collected from 80 different broiler breeder flocks were included in this study. Antibiotic susceptibility testing was performed using disk diffusion method according to Clinical and Laboratory Standards Institute guidelines. Minimal inhibitory concentrations (MICs) of five antimicrobial agents were determined by Etest. PCR and sequencing were used to detect the blaESBL genes. E. coli were detected in the ovaries of thirty seven out of 80 (46.25%) sampled flocks. High levels of resistance to various first-line antimicrobial agents were recorded in E. coli isolates. This study showed that 89.18% of E. coli isolates were multidrug resistant (MDR). Furthermore, MDR extended-spectrum β-lactamases (ESBL)-producing E. coli were detected in the ovaries of four different broiler breeder flocks. Molecular characterization revealed that three isolates harboured blaCTX-M-1 gene and one isolate expressed blaSHV-12 gene. In addition, one blaCTX-M-1 -producing E. coli co-harboured the blaTEM-1 gene. These findings would contribute to a better epidemiological understanding of MDR E. coli for improve existing preventive strategies in order to reduce the dissemination of antimicrobial resistance in the broiler production system.

The public washroom - friend or foe? An observational study of washroom cleanliness combined with microbiological investigation of hand hygiene facilities

BackgroundMany people use handwashing and hand-drying facilities in public washrooms under the impression that these amenities are hygienic. However, such facilities may be potential sites for the transmission of pathogenic bacteria. This study aimed to examine the hygiene facilities provided including handwashing and hand-drying facilities in public washrooms. Total bacterial counts and species identification were determined for hand-drying facilities. Antimicrobial susceptibilities were performed.MethodsThe bacterial contamination levels of 55 public washrooms ranging in category from low class communities to high end establishments, were examined. The hygienic environment and facilities of the washrooms were analysed using an electronic checklist to facilitate immediate data entry. Pre-moistened sterile swabs were used to collect samples from areas around the outlet of paper towel dispensers, air outlet of air dryers, exit door handles and paper towels in the washrooms. Total bacterial counts were performed and isolates identified using matrix-assisted laser desorption ionisation time-of-flight mass spectrometry. Antimicrobial susceptibility was determined by disk diffusion.ResultsThe high and middle-income categories washrooms generally had cleaner facilities and environment followed by those in low categories. Fifty-two bacterial species were identified from the 55 investigated washrooms. Over 97% of the pathogenic Staphylococcus spp. tested were resistant to at least one first-line antimicrobial therapeutic agent, including penicillin, cefoxitin, erythromycin, co-trimoxazole, clindamycin and gentamicin, and 22.6% demonstrated co-resistance to at least three antimicrobial agents, with co-resistance to penicillin, erythromycin and clindamycin being the most common.ConclusionOur findings suggest that hand-drying facilities in public washrooms can act as reservoirs of drug-resistant bacteria. The importance of frequent cleaning and maintenance of public washrooms to promote safe hand hygiene practices for the public are emphasised.

Integrative metagenomic and biochemical studies on rifamycin ADP-ribosyltransferases discovered in the sediment microbiome

Antibiotic resistance is a serious and growing threat to human health. The environmental microbiome is a rich reservoir of resistomes, offering opportunities to discover new antibiotic resistance genes. Here we demonstrate an integrative approach of utilizing gene sequence and protein structural information to characterize unidentified genes that are responsible for the resistance to the action of rifamycin antibiotic rifampin, a first-line antimicrobial agent to treat tuberculosis. Biochemical characterization of four environmental metagenomic proteins indicates that they are adenosine diphosphate (ADP)-ribosyltransferases and effective in the development of resistance to FDA-approved rifamycins. Our analysis suggests that even a single residue with low sequence conservation plays an important role in regulating the degrees of antibiotic resistance. In addition to advancing our understanding of antibiotic resistomes, this work demonstrates the importance of an integrative approach to discover new metagenomic genes and decipher their biochemical functions.

Point prevalence surveys of antimicrobial use among eight neonatal intensive care units in India: 2016

BackgroundInformation about antimicrobial use is scarce and poorly understood among neonatal intensive care units (NICUs) in India. In this study, we describe antimicrobial use in eight NICUs using four point prevalence surveys (PPSs). MethodsAs part of the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children (GARPEC) study, one-day, cross-sectional, hospital-based PPSs were conducted four times between 1 February 2016 and 28 February 2017 in eight NICUs. Using a standardized web-based electronic data entry form, detailed data were collected for babies on antimicrobials. ResultsA total of 403 babies were admitted to NICUs across all survey days, and 208 (51.6%) were prescribed one or more antimicrobials. Among 208 babies, 155 (74.5%) were prescribed antimicrobials for treatment of an active infection. Among 155 babies with an active infection, treatment was empiric in 109 (70.3%). Sepsis (108, 49.1%) was the most common reason for prescribing antimicrobials. Amikacin (17%) followed by meropenem (12%) were the two most commonly prescribed antimicrobials. For community-acquired sepsis, piperacillin-tazobactam (17.5%) was the most commonly prescribed drug. A combination of ampicillin and gentamicin was prescribed in only two babies (5%). ConclusionsThe recommended first-line antimicrobial agents, ampicillin and gentamicin, were rarely prescribed in Indian NICUs for community acquired neonatal sepsis.

Antimicrobial activity of preparations after combined cultivation of lactic acid bacteria and yeast strains.

Use of antimicrobials in both human and animal populations over the past several decades has led to the emergence of multidrug-resistant bacteria populations that are resistant to many commercially available drugs. For example, acquired resistance to first-line antimicrobial agents increasingly complicates the management of extra-intestinal infections due to Escherichia coli, which are a major source of illness and death. The continued development of new classes of natural antimicrobial agents, possessing antibacterial activity, has become of increasing importance for medicine and veterinary. So, selection of lactic acid bacteria and yeast strains for their combined cultivation with the aim of increasing of the activity is topical. It was shown that during combined cultivation of the lactic acid bacteria with probiotic properties and yeast strains, antimicrobial activity depends on the genus and species to which the strain of lactic acid bacteria and yeast belongs. They inhibited the growth of multidrug-resistant bacteria with better efficiency. Increasing of the antimicrobial activity can be explained by the synergetic effect of products of cultures metabolism and by interaction between lactic acid bacteria cells with the cell wall of yeasts. Our data showed perspectives of combined cultivation of yeast and lactic acid bacteria for creation of a new class of antimicrobial preparations with high antibacterial activity and broad spectrum of action. Preparation can be recommended for treatment of animals.

Increasing Incidence of Listeriosis and Infection-associated Clinical Outcomes.

BackgroundListeriosis caused by Listeria monocytogenes has a high case-fatality rate (CFR) of approximately 20% to 30%. An increasing incidence of listeriosis has been reported in many countries recently. We investigated the annual incidence, clinical characteristics, and outcomes of listeriosis at three different hospitals in Korea and evaluated the effects of appropriate empiric antimicrobial treatments on patient outcomes.MethodsWe retrospectively collected the data of all culture-positive cases of human listeriosis from three hospitals of different sizes in Korea during 2006–2016 and calculated the annual number of cases and incidence per 100,000 admissions.ResultsA total of 58 patients with L. monocytogenes were included in this study. The incidence of listeriosis was significantly higher in 2013–2016 than in 2006–2012 (RR 3.1; 95% CI 1.79–5.36; P<0.001), mainly because of an increase in patients over 60 years of age (RR 3.69; 95% CI 1.70–8.02; P<0.001). Multivariate analysis showed that healthcare-associated infection (adjusted OR, 12.15; 95% CI, 2.56–86.01; P=0.004) and empirical treatment with first-line antimicrobial agents (adjusted OR, 0.08; 95% CI, 0.00–0.63; P=0.044) were associated with CFR.ConclusionsHealthcare-associated infections caused by L. monocytogenes are associated with high CFR. Adequate initial empirical treatments could reduce CFR, suggesting that careful consideration of an empirical antimicrobial regimen is warranted for elderly or immunocompromised patients admitted to the hospital.

Use of Ceftaroline Fosamil in Children: Review of Current Knowledge and its Application.

Ceftaroline is a novel cephalosporin recently approved in children for treatment of acute bacterial skin and soft tissue infections and community-acquired bacterial pneumonia (CABP) caused by methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae and other susceptible bacteria. With a favorable tolerability profile and efficacy proven in pediatric patients and excellent in vitro activity against resistant Gram-positive and Gram-negative bacteria, ceftaroline may serve as a therapeutic option for polymicrobial infections, CABP caused by penicillin- and ceftriaxone-resistant S. pneumoniae and resistant Gram-positive infections that fail first-line antimicrobial agents. However, limited data are available on tolerability in neonates and infants younger than 2 months of age, and on pharmacokinetic characteristics in children with chronic medical conditions and those with invasive, complicated infections. In this review, the microbiological profile of ceftaroline, its mechanism of action, and pharmacokinetic profile will be presented. Additionally, clinical evidence for use in pediatric patients and proposed place in therapy is discussed.

Plesiomonas shigelloides Revisited.

After many years in the family Vibrionaceae, the genus Plesiomonas, represented by a single species, P. shigelloides, currently resides in the family Enterobacteriaceae, although its most appropriate phylogenetic position may yet to be determined. Common environmental reservoirs for plesiomonads include freshwater ecosystems and estuaries and inhabitants of these aquatic environs. Long suspected as being an etiologic agent of bacterial gastroenteritis, convincing evidence supporting this conclusion has accumulated over the past 2 decades in the form of a series of foodborne outbreaks solely or partially attributable to P. shigelloides. The prevalence of P. shigelloides enteritis varies considerably, with higher rates reported from Southeast Asia and Africa and lower numbers from North America and Europe. Reasons for these differences may include hygiene conditions, dietary habits, regional occupations, or other unknown factors. Other human illnesses caused by P. shigelloides include septicemia and central nervous system disease, eye infections, and a variety of miscellaneous ailments. For years, recognizable virulence factors potentially associated with P. shigelloides pathogenicity were lacking; however, several good candidates now have been reported, including a cytotoxic hemolysin, iron acquisition systems, and lipopolysaccharide. While P. shigelloides is easy to identify biochemically, it is often overlooked in stool samples due to its smaller colony size or relatively low prevalence in gastrointestinal samples. However, one FDA-approved PCR-based culture-independent diagnostic test system to detect multiple enteropathogens (FilmArray) includes P. shigelloides on its panel. Plesiomonads produce β-lactamases but are typically susceptible to many first-line antimicrobial agents, including quinolones and carbapenems.