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Microorganisms Dec 2021Hospitalization and treatment with antibiotics increase the risk of acquiring multidrug-resistant bacteria due to antibiotic-mediated changes in patient microbiota. This...
Hospitalization and treatment with antibiotics increase the risk of acquiring multidrug-resistant bacteria due to antibiotic-mediated changes in patient microbiota. This study aimed to investigate how broad- and narrow-spectrum antibiotics affect the gut microbiome and the resistome in antibiotic naïve patients during neurointensive care. Patients admitted to the neurointensive care unit were treated with broad-spectrum (meropenem or piperacillin/tazobactam) or narrow-spectrum antibiotic treatment (including ciprofloxacin, cefuroxime, vancomycin and dicloxacillin) according to clinical indications. A rectal swab was collected from each patient before and after 5-7 days of antibiotic therapy ( = 34), respectively. Shotgun metagenomic sequencing was performed and the composition of metagenomic species (MGS) was determined. The resistome was characterized with CARD RGI software and the CARD database. As a measure for selection pressure in the patient, we used the sum of the number of days with each antibiotic (antibiotic days). We observed a significant increase in richness and a tendency for an increase in the Shannon index after narrow-spectrum treatment. For broad-spectrum treatment the effect was more diverse, with some patients increasing and some decreasing in richness and Shannon index. This was studied further by comparison of patients who had gained or lost >10 MGS, respectively. Selection pressure was significantly higher in patients with decreased richness and a decreased Shannon index who received the broad treatment. A decrease in MGS richness was significantly correlated to the number of drugs administered and the selection pressure in the patient. Bray-Curtis dissimilarities were significant between the pre- and post-treatment of samples in the narrow group, indicating that the longer the narrow-spectrum treatment, the higher the differences between the pre- and the post-treatment microbial composition. We did not find significant differences between pre- and post-treatment for both antibiotic spectrum treatments; however, we observed that most of the antibiotic class resistance genes were higher in abundance in post-treatment after broad-spectrum treatment.
PubMed: 34946144
DOI: 10.3390/microorganisms9122542 -
Antibiotics (Basel, Switzerland) Dec 2021Gram-negative Tripartite Resistance Nodulation and cell Division (RND) superfamily efflux pumps confer various functions, including multidrug and bile salt resistance,...
Gram-negative Tripartite Resistance Nodulation and cell Division (RND) superfamily efflux pumps confer various functions, including multidrug and bile salt resistance, quorum-sensing, virulence and can influence the rate of mutations on the chromosome. Multidrug RND efflux systems are often characterized by a wide substrate specificity. Similarly to many other RND efflux pump systems, AcrAD-TolC confers resistance toward SDS, novobiocin and deoxycholate. In contrast to the other pumps, however, it in addition confers resistance against aminoglycosides and dianionic β-lactams, such as sulbenicillin, aztreonam and carbenicillin. Here, we could show that AcrD from confers resistance toward several hitherto unreported AcrD substrates such as temocillin, dicloxacillin, cefazolin and fusidic acid. In order to address the molecular determinants of the AcrD substrate specificity, we conducted substitution analyses in the putative access and deep binding pockets and in the TM1/TM2 groove region. The variants were tested in ΔΔ against β-lactams oxacillin, carbenicillin, aztreonam and temocillin. Deep binding pocket variants N136A, D276A and Y327A; access pocket variant R625A; and variants with substitutions in the groove region between TM1 and TM2 conferred a sensitive phenotype and might, therefore, be involved in anionic β-lactam export. In contrast, lower susceptibilities were observed for cells harbouring deep binding pocket variants T139A, D176A, S180A, F609A, T611A and F627A and the TM1/TM2 groove variant I337A. This study provides the first insights of side chains involved in drug binding and transport for AcrD from .
PubMed: 34943706
DOI: 10.3390/antibiotics10121494 -
Journal of Chromatography. A Nov 2021The presence of antibiotics in the aquatic environment is becoming one of the main research focus of scientists and policy makers. Proof of that is the inclusion of four...
The presence of antibiotics in the aquatic environment is becoming one of the main research focus of scientists and policy makers. Proof of that is the inclusion of four antibiotics, amongst which is amoxicillin, in the EU Watch List (WL) (Decision 2020/1161/EU)) of substances for water monitoring. The accurate quantification of amoxicillin in water at the sub-ppb levels required by the WL is troublesome due to its physicochemical properties. In this work, the analytical challenges related to the determination of amoxicillin, and six related penicillins (ampicillin, cloxacillin, dicloxacillin, penicillin G, penicillin V and oxacillin), have been carefully addressed, including sample treatment, sample stability, chromatographic analysis and mass spectrometric detection by triple quadrupole. Given the low recoveries obtained using different solid-phase extraction cartridges, we applied the direct injection of water samples using a reversed-phase chromatographic column that allowed working with 100% aqueous mobile phase. Matrix effects were evaluated and corrected using the isotopically labelled internal standard or correction factors based on signal suppression observed in the analysis of spiked samples. The methodology developed was satisfactorily validated at 50 and 500 ng L for the seven penicillins studied, and it was applied to different types of water matrices, revealing the presence of ampicillin in one surface water sample and cloxacillin in three effluent wastewater samples.
Topics: Amoxicillin; Ampicillin; Chromatography, High Pressure Liquid; European Union; Penicillins; Solid Phase Extraction; Water
PubMed: 34662823
DOI: 10.1016/j.chroma.2021.462605 -
Rural and Remote Health Oct 2021The Gram-negative organism Aeromonas is found in freshwater and marine environments and can cause a range of disease in humans, most commonly gastrointestinal illness...
CONTEXT
The Gram-negative organism Aeromonas is found in freshwater and marine environments and can cause a range of disease in humans, most commonly gastrointestinal illness and soft tissue infections. The severity of soft tissue infections can vary, ranging from cellulitis to rapidly spreading soft tissue infection. Prompt recognition of this pathogen is needed as empirical antibiotics for cellulitis generally do not provide sufficient cover for Aeromonas. Additionally, while cellulitis is generally managed medically, early surgical intervention may be required when Aeromonas is the causative pathogen.
ISSUES
A Caucasian male aged 39 years injured his right foot falling in a creek bed in the Darling Downs region of rural Queensland, sustaining a laceration in the webbing between his first and second toes. He was seen in two rural hospitals following this event, with oral antibiotics prescribed following his second presentation to cover for a localised soft tissue infection. Circumstances meant he did not take these, and he finally presented to a third hospital after noting erythema tracking up his leg and discharge emanating from the wound on his foot. He was admitted and commenced on empirical antibiotics, however severity of the infection necessitated surgical team involvement and multiple debridements. Due to the extent of tissue removal, a skin graft was required. Intraoperative specimens revealed polymicrobial Aeromonas as the causative pathogen.
LESSONS LEARNED
This case report documents a polymicrobial soft tissue infection in a systemically well young male requiring prompt surgical intervention, even without systemic symptoms of illness. Lack of early recognition of risk factors for infection may have delayed appropriate antibiotic therapy. It highlights the importance of early recognition and appropriate antibiotic cover to prevent spreading infection in individuals in whom Aeromonas may be the suspected pathogen. Empirical antibiotics for cellulitis generally do not include the agents to which Aeromonas is susceptible, hence guidelines recommend a regime of trimethoprim-sulfamethoxazole or ciprofloxacin in addition to either dicloxacillin or flucloxacillin. Initiation of appropriate antibiotics earlier in this case may have prevented the need for surgical intervention. This case also demonstrates that early surgical referral and intervention may be warranted in suspected Aeromonas infections.
Topics: Aeromonas; Aeromonas hydrophila; Anti-Bacterial Agents; Cellulitis; Gram-Negative Bacterial Infections; Humans; Male; Queensland
PubMed: 34655515
DOI: 10.22605/RRH6710 -
BMC Infectious Diseases Oct 2021Delafloxacin is a novel fluoroquinolone with broad antibacterial activity against pathogens causing acute bacterial skin and skin structure infections (ABSSSI). This...
BACKGROUND
Delafloxacin is a novel fluoroquinolone with broad antibacterial activity against pathogens causing acute bacterial skin and skin structure infections (ABSSSI). This network meta-analysis (NMA) was conducted to evaluate the relative efficacy of delafloxacin versus other comparators used for managing patients with ABSSSI.
METHODS
A systematic literature review was conducted to identify randomised controlled trials (RCTs) evaluating adults (≥ 18 years) with ABSSSI, complicated SSSI (cSSSI), complicated skin and soft tissue infections (cSSTI) or severe cellulitis with pathogen of gram-positive, gram-negative, or mixed aetiology. OVID MEDLINE, Embase, Epub Ahead of Print, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews were searched from inception through 12 April 2019. A feasibility assessment was conducted, followed by an NMA, which was run in a Bayesian framework. The interventions included in the NMA encompassed monotherapy or combination therapies of amoxicillin/clavulanate, ampicillin/sulbactam, ceftaroline, ceftobiprole, dalbavancin, daptomycin, delafloxacin, fusidic acid, iclaprim, linezolid, omadacycline, oxacillin + dicloxacillin, standard therapy, tedizolid, telavancin, tigecycline, vancomycin, vancomycin + aztreonam and vancomycin + linezolid.
RESULTS
A feasibility assessment was performed and evidence networks were established for composite clinical response (n = 34 studies), early clinical response (n = 16 studies) and microbiological response (n = 14 studies) in the overall study population, composite clinical response (n = 4 studies) in obese subpopulation and for composite clinical response (n = 18 studies) and microbiological response (n = 14 studies) in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. Delafloxacin performed significantly better than fusidic acid, iclaprim, vancomycin, and ceftobiprole for composite clinical response. Delafloxacin was comparable to dalbavancin, daptomycin, fusidic acid, iclaprim, linezolid, omadacycline, tedizolid, vancomycin, vancomycin + aztreonam and vancomycin + linezolid in the analysis of early clinical response, whereas for microbiological response, delafloxacin was comparable to all interventions. In the obese subpopulation, the results favoured delafloxacin in comparison to vancomycin, whilst the results were comparable with other interventions among the MRSA subpopulation.
CONCLUSIONS
Delafloxacin is a promising new antibiotic for ABSSSI demonstrating greater improvement (composite clinical response) compared to ceftobiprole, fusidic acid, iclaprim, telavancin and vancomycin and comparable effectiveness versus standard of care for all outcomes considered in the study.
Topics: Adult; Fluoroquinolones; Humans; Network Meta-Analysis; Skin Diseases, Infectious; Systematic Reviews as Topic
PubMed: 34610820
DOI: 10.1186/s12879-021-06736-x -
Journal of Analytical Methods in... 2021Novel, accurate, selective, and rapid high-performance liquid chromatography mass spectrometry method was developed for simultaneous analysis of amoxicillin trihydrate,...
Novel, accurate, selective, and rapid high-performance liquid chromatography mass spectrometry method was developed for simultaneous analysis of amoxicillin trihydrate, dicloxacillin sodium, and their official impurity 6-aminopenicillanic acid. The chromatographic separation was carried out by applying the mixture on a C column (3.5 m ps, 100 mm × 4.6 mm id) using acetonitrile:water (65 : 35 by volume) as a mobile phase within only 4 min. The quantitative analysis was executed using single quadrupole mass spectrometer in which electrospray ionization, selected ion monitoring, and negative mode were operated. The retention times were 1.61, 2.54, and 3.50 mins for amoxicillin, 6-aminopenicillanic acid, and dicloxacillin, respectively. The method was validated in linear ranges of 2-28 g mL, 2-35 g mL, and 1-10 g mL for amoxicillin, dicloxacillin, and 6-aminopenicillanic acid, respectively. The results obtained from the suggested HPLC/MS were statistically compared with those obtained from the reported HPLC method, where no significant difference appeared respecting accuracy and precision. According to the analytical eco-scale assessment method, the proposed method was proved to be greener than the reported one, where the analysis time and the amount of the wasted effluent decreased.
PubMed: 34221533
DOI: 10.1155/2021/5570938 -
Ugeskrift For Laeger May 2021Toxic shock syndrome is a potentially deadly toxin-mediated disease in which quick diagnosis is imperative for treatment and prognosis. This is a case report of a...
Toxic shock syndrome is a potentially deadly toxin-mediated disease in which quick diagnosis is imperative for treatment and prognosis. This is a case report of a 21-year-old woman admitted with high fever, confusion, petechial rash and hypotension. During catherisation a tampon was found, and from a vaginal swab Staphylococcus aureus was grown. The patient was hospitalised for eight days, two of which were at the intensive care unit for norepinephrine infusion for hypotension. She was successfully treated with the antibiotics dicloxacillin and clindamycin.
Topics: Adult; Anti-Bacterial Agents; Clindamycin; Female; Humans; Shock, Septic; Staphylococcal Infections; Staphylococcus aureus; Young Adult
PubMed: 33998442
DOI: No ID Found -
International Archives of Allergy and... 2021Intradermal testing with delayed reading (IDTdr), used routinely in many centers, may identify delayed reactions to penicillins. However, few studies have compared the...
BACKGROUND
Intradermal testing with delayed reading (IDTdr), used routinely in many centers, may identify delayed reactions to penicillins. However, few studies have compared the results of IDTdr with drug provocation test (DPT). The aim of this study was to examine the proportion of provocation-positive patients testing positive on IDTdr.
METHODS
Fifty-seven patients with a positive DPT occurring >2 h after intake of penicillin V, dicloxacillin, pivampicillin, or amoxicillin had an IDTdr with penicillin G, amoxicillin, ampicillin, and dicloxacillin. A control group included 18 patients with negative DPTs with the suspected penicillin.
RESULTS
In total 25% (n = 14) of provocation-positive patients tested positive on IDTdr. Among patients with positive IDTdr, 9/14 (64%) versus 11/43 (26%) in the IDTdr negative group (p < 0.05) had required oral steroids to treat skin reactions following DPT. No other differences between IDTdr positive and negative groups were found. No controls had a positive IDTdr.
CONCLUSION
Investigating with IDTdr would have identified 25% of patients with a DPT-verified allergy with delayed reactions. It is difficult to target subgroups who will test positive on IDTdr. There were more patients who tested positive on IDT who had received oral steroids after DPT, and this may be an indication that skin reaction severity plays a role in skin testing diagnostics. Further potential predictors for positivity of IDTdr, such as duration of skin symptoms, should be assessed in large studies in order to optimize the investigations of nonimmediate drug allergic reactions.
Topics: Anti-Bacterial Agents; Drug Hypersensitivity; Humans; Hypersensitivity, Delayed; Penicillin G; Penicillins; Skin Tests; Symptom Assessment
PubMed: 33873191
DOI: 10.1159/000515080 -
Archives of Microbiology Aug 2021The continual increase in resistance to antibacterial drugs has become a major public health problem, and their indiscriminate use in agriculture, aquaculture, and the...
The continual increase in resistance to antibacterial drugs has become a major public health problem, and their indiscriminate use in agriculture, aquaculture, and the treatment of human and animal diseases has severely contributed to the occurrence and spread of multidrug resistance genes. This study phylogenetically characterized multidrug-resistant bacteria isolated from seafood cocktails. Seafood cocktail dishes from 20 establishments on public roads were sampled. Samples were grown on TCBS agar and blood agar. Forty colonies with different macro- and microscopic characteristics were isolated. The 16S rRNA gene V4 and V6 hypervariable regions were amplified, sequenced and phylogenetically analyzed. Antibacterial drug resistance was determined by disk diffusion assay. Isolated bacteria were identical to species of the genera Enterococcus, Proteus, Vibrio, Staphylococcus, Lactococcus, Vagococcus, Micrococcus, Acinetobacter, Enterobacter, and Brevibacterium, with 75-100% presenting resistance or intermediate resistance to dicloxacillin, ampicillin, and penicillin; 50-70% to cephalosporins; 30-67.5% to amikacin, netilmicin and gentamicin; 40% to nitrofurantoin and other antibacterial drugs; 25% to chloramphenicol; and 2.5% to trimethoprim with sulfamethoxazole. In general, 80% of the bacteria showed resistance to multiple antibiotics. The high degree of bacterial resistance to antibacterial drugs indicates that their use in producing raw material for marine foods requires established guidelines and the implementation of good practices.
Topics: Bacteria; Drug Resistance, Multiple, Bacterial; Phylogeny; Seafood
PubMed: 33864113
DOI: 10.1007/s00203-021-02319-1 -
Clinical and Experimental Emergency... Mar 2021Centipede stings are a common problem in tropical countries. Current treatment guidelines do not include recommendations for antibiotic prophylaxis to prevent the...
OBJECTIVE
Centipede stings are a common problem in tropical countries. Current treatment guidelines do not include recommendations for antibiotic prophylaxis to prevent the associated bacterial infection since no previous study has assessed the effectiveness of antibiotic treatment in patients bitten by centipedes. Thus, this study aimed to compare the effectiveness of antibiotic prophylaxis over placebo for the skin infections that occur after a centipede sting.
METHODS
In this randomized, double-blind, multi-center clinical trial conducted in the emergency departments in four hospitals, patients with any history of a centipede sting were prospectively enrolled and divided randomly into two groups. One group received dicloxacillin and the other a placebo. The primary outcome was the incidence of wound infection 3 to 5 days after the centipede sting.
RESULTS
From December 2014 to October 2015, a total of 83 patients were enrolled in the study and were randomized into antibiotic (n=43) and placebo (n=40) groups. Two patients in the antibiotic group developed wound infections, while none showed wound infection in the placebo group (5% vs. 0%). The wound infection rate did not differ significantly between the two groups (P=0.496).
CONCLUSION
Antibiotic prophylaxis may be unnecessary in cases of centipede stings. Proper wound care is an adequate and appropriate treatment for patients with centipede stings. However, the patient should be re-evaluated for detection of secondary bacterial infection.
PubMed: 33845522
DOI: 10.15441/ceem.20.110