Number Of Different Antibiotics Research Articles

Allergies to antibiotics among US women with uncomplicated urinary tract infection.

Uncomplicated urinary tract infections (uUTI) are generally treated empirically with antibiotics. However, antibiotic allergies limit the available oral treatment options for some patients. We assessed the proportion of self-reported antibiotic allergies among US women with uUTI. We performed a cross-sectional survey of US women (≥18 years) with a self-reported uUTI in the previous 60 days and an oral antibiotic prescription. Participants completed an online questionnaire about their most recent uUTI episode. Descriptive self-reported allergy data were stratified into subgroups by whether the participant had recurrent UTI (≥2 uUTIs in the past 6 months or ≥3 uUTIs in past 12 months, including the index episode), the number of different antibiotics given for the index episode (1, 2, ≥3), and whether the treatment was clinically aligned according to Infectious Diseases Society of America uUTI guidelines. Overall, 375 participants completed the questionnaire. The most commonly prescribed antibiotics were trimethoprim-sulfamethoxazole (SXT; 38.7%), ciprofloxacin (22.7%), and nitrofurantoin (18.9%). Most participants (62.7%) received only 1 antibiotic for their uUTI, and most (56.5%) were classified as having a non-recurrent uUTI. No antibiotic allergies were reported for most participants (69.3%), with 24.0% reporting 1 antibiotic allergy and 6.7% reporting ≥2 antibiotic allergies. Allergies to ≥2 antibiotic types were more common among participants classified as having recurrent uUTI, or who used multiple antibiotics to treat their uUTI. The most common allergy was to SXT (15.7%), followed by amoxicillin-clavulanate (8.3%) and ciprofloxacin (5.3%). Similar allergy trends were seen across subgroups, except higher rates of ciprofloxacin allergy were seen in participants given multiple antibiotics. Antibiotic allergies were relatively frequent in this uUTI cohort and the most common allergy was to SXT, which was the most prescribed antibiotic. Allergies to antibiotics reduce the available treatment options for uUTI in some patients.

General Practitioner-Related Factors Associated with Antibiotic Prescription in Community-Dwelling Adult Population

Background: The extensive use of antibiotics has contributed to the development of antibiotic resistance. Understanding the factors behind the attitude of physicians in prescribing antibiotics may be useful to address educational interventions to sensitize them to a more rational use of these drugs. This study aimed to evaluate the general practitioners’ (GPs) characteristics potentially associated with antibiotic prescription in community-dwelling adults from 2000 to 2019. Method: Multivariable linear regression models were performed to evaluate the association of GPs’ characteristics with the mean number of different antibiotics prescribed and the mean number of Defined Daily Doses (DDD) prescribed per patient. Results: We found that GPs older than 60 years prescribed a smaller number of different antibiotics per patient compared to 30–40 years old GPs (mean (standard error) 1.4 (0.5) vs. 1.8 (0.4)). In contrast older GPs prescribed more DDD compared to younger ones (28.9 (0.1) vs. 27.3 (0.3)). GPs prescribed 29 (0.1) DDD for >200 patients on polypharmacy vs. 28 (0.1) DDD for <100 patients on polypharmacy. The mean number of DDD prescribed increased by 5 units and by 16 units for each refill and switch, respectively. Conclusions: Age and number of patients in polypharmacy in charge were found to be associated with higher antibiotic prescriptions. The knowledge of the GPs-related factors could allow the stakeholders to design interventions to sensitize them to a more appropriate use of antibiotics in view of the increasing issue of antibiotic resistance.

Impact of Prior Antibiotic Use in Primary Care on Escherichia coli Resistance to Third Generation Cephalosporins: A Case-Control Study.

Research is lacking on the reversibility of antimicrobial resistance (AMR). Thus, we aimed to determine the influence of previous antibiotic use on the development and decay over time of third generation cephalosporin (3GC)-resistance of E. coli. Using the database of hospital laboratories of the Autonomous Province of Bolzano/Bozen (Italy), anonymously linked to the database of outpatient pharmaceutical prescriptions and the hospital discharge record database, this matched case-control study was conducted including as cases all those who have had a positive culture from any site for 3GC resistant E. coli (3GCREC) during a 2016 hospital stay. Data were analyzed by conditional logistic regression. 244 cases were matched to 1553 controls by the date of the first isolate. Male sex (OR 1.49, 95% CI 1.10–2.01), older age (OR 1.11, 95% CI 1.02–1.21), the number of different antibiotics taken in the previous five years (OR 1.20, 95% CI 1.08–1.33), at least one antibiotic prescription in the previous year (OR 1.92, 95% CI 1.36–2.71), and the diagnosis of diabetes (OR 1.57, 95% CI 1.08–2.30) were independent risk factors for 3GCREC colonization/infection. Patients who last received an antibiotic prescription two years or three to five years before hospitalization showed non-significant differences with controls (OR 0.97, 95% CI 0.68–1.38 and OR 0.85, 95% CI 0.59–1.24), compared to an OR of 1.92 (95% CI 1.36–2.71) in those receiving antibiotics in the year preceding hospitalization. The effect of previous antibiotic use on 3GC-resistance of E. coli is highest after greater cumulative exposure to any antibiotic as well as to 3GCs and in the first 12 months after antibiotics are taken and then decreases progressively.

The microbial diversity following antibiotic treatment of Clostridioides difficile infection

BackgroundClostridioides difficile (C. difficile) is a major nosocomial pathogen that infects the human gut and can cause diarrheal disease. A dominant risk factor is antibiotic treatment that disrupts the normal gut microbiota. The aim of the study was to examine the correlation between antibiotic treatment received prior to C. difficile infection (CDI) onset and patient gut microbiota.MethodsStool samples were collected from patients with CDI, presenting at the Baruch Padeh Medical Center Poriya, Israel. Demographic and clinical information, including previous antibiotic treatments, was collected from patient charts, and CDI severity score was calculated. Bacteria were isolated from stool samples, and gut microbiome was analyzed by sequencing the 16S rRNA gene using the Illumina MiSeq platform and QIIME2.ResultsIn total, 84 patients with CDI were enrolled in the study; all had received antibiotics prior to disease onset. Due to comorbidities, 46 patients (55%) had received more than one class of antibiotics. The most common class of antibiotics used was cephalosporins (n = 44 cases). The intestinal microbiota of the patients was not uniform and was mainly dominated by Proteobacteria. Differences in intestinal microbiome were influenced by the different combinations of antibiotics that the patients had received (p = 0.022)ConclusionsThe number of different antibiotics administered has a major impact on the CDI patients gut microbiome, mainly on bacterial richness.

Attachment and antibiotic response of early-stage biofilms studied using resonant hyperspectral imaging

Many bacterial species readily develop biofilms that act as a protective matrix against external challenge, e.g., from antimicrobial treatment. Therefore, biofilms are often responsible for persistent and recurring infections. Established methods for studying biofilms are either destructive or focus on the biofilm’s surface. A non-destructive method that is sensitive to the underside of the biofilm is highly desirable, as it allows studying the penetration of antibiotics through the film. Here, we demonstrate that the high surface sensitivity of resonant hyperspectral imaging provides this capability. The method allows us to monitor the early stages of Escherichia coli biofilm formation, cell attachment and microcolony formation, in-situ and in real-time. We study the response of the biofilm to a number of different antibiotics and verify our observations using confocal microscopy. Based on this ability to closely monitor the surface-bound cells, resonant hyperspectral imaging gives new insights into the antimicrobial resistance of biofilms.

Reconstruction of sternal defects after sternotomy with postoperative osteomyelitis, using a unilateral pectoralis major advancement muscle flap

Background: The pectoralis major flap, which is usually harvested bilaterally, is considered a workhorse flap in the reconstruction of sternal defects. After a median sternotomy for open heart surgery, 1%-3% of patients develop deep infection and dehiscence of the sternal wound, some of which will eventually require reconstructive surgery. Our aim was to describe the clinical feasibility and associated complications of the unilateral pectoralis major advancement flap in the reconstruction of sternal defects. Methods: A retrospective analysis of all adult patients who were operated on using a unilateral pectoralis major flap for reconstruction of the chest wall at the Linköping University Hospital during 2008–18 was made using data retrieved from medical records. Results: Forty-three patients had reconstructions with unilateral pectoralis major flaps. Three flaps failed completely, and another 10 patients developed complications that required further operation. The factors that were independently associated with loss of the flaps and complications were: older age, male sex, the number of different antibiotics used, and a long duration of treatment with negative wound pressure. Fewer wound revisions before the reconstruction resulted in more complications. The factors that were independently associated with prolonged time to complete healing were emergency reoperation after the initial operation and complications after reconstruction. Conclusion: The unilateral pectoralis major advancement flap has proved to be a useful technique in the reconstruction of most sternal defects after sternal wound infection in older patients. There is, however, need for a follow-up study on a larger number of procedures to evaluate the long-term outcome compared with other methods of sternal reconstruction.

186. Risk Factors for Extended Spectrum β-Lactamase Bacteremia and External Application of a Clinical Prediction Tool

BackgroundExtended spectrum β-lactamase (ESBL) bacteria are resistant to many antibiotics, which increases the risk of inadequate early antibiotic therapy. A previous single-center study had created a prediction tool to assist clinicians in identifying patients at risk for ESBL bloodstream infections. The purpose of our research project was to assess validity of this tool while also identifying risk factors for ESBL bacteremia within our own institution, which would allow for assessment of alternative prediction tools.MethodsWe performed a retrospective chart review of adult patients admitted to an urban university hospital who were found to have bacteremia with Escherichia coli, Klebsiella pneumoniae, and/or Klebsiella oxytoca between October 2016 and April 2018. Demographics and comorbidities were assessed, along with other potential risk factors including exposure to antibiotics and hospitalizations within the past 6 months.ResultsA total of 214 instances of bacteremia were identified and 14% were due to ESBL organisms. Risk factors for ESBL bacteremia in our cohort included history of positive culture for ESBL (RR = 5.9) or MRSA (RR = 3.5) and antibiotic usage in the past 6 months (RR = 2.3). Patients with ESBL bacteremia were hospitalized longer (mean 16 days vs. 6 days for non-ESBL), received longer durations of antibiotic therapy (11.7 days vs. 5.3 days), and were exposed to greater numbers of different antibiotics (1.9 vs. 0.7) in the previous 6 months. Multivariate logistic regression showed that history of prior ESBL infection (OR 14.7, CI 1.8–120) and increasing number of different antibiotic classes administered in the prior 6 months (OR 4.3, CI 1.7–11.2) were significant risk factors for ESBL bacteremia. The previously created prediction tool did not sufficiently differentiate higher and lower risk for ESBL bacteremia in our cohort.ConclusionAlthough risk factors were similar, the previously derived stepwise prediction tool did not predict ESBL bacteremia in our external cohort. Point-based prediction modeling might better assess risk across institutions. Additionally, the number of different antibiotics received was associated with risk for ESBL bacteremia and should be investigated further.Disclosures All authors: No reported disclosures.

2575. Dramatic Time-Dependent Changes of Bacterial and Fungal Taxonomic Signatures in 4 Body Regions of ICU Patients

BackgroundIt has been hypothesized that intensive care unit (ICU)-related complications like nosocomial pneumonia or gastrointestinal dysfunction are associated with disturbances of normal host microorganisms. However, these alterations are largely unknown in ICU patients. The bacterio- and mycobiota in 4 body regions in 14 ICU patients was investigated after admission until death or discharge to other wards.MethodsMedical ICU patients were sampled with pharyngeal swabs, endotracheal aspirates, gastric secretions and stools or rectal swabs (in constipated patients). V1-V2 (16S rRNA gene) and eukaryoitic ITS sequencing was performed as previously described as well as denoizing, transformation into amplicon sequence variants and analysis using qiime2 and LEfSe (LDA Score > 3.0, P-value < 0.05). For sequence classification databases SILVA 132 (16S) and UNITE version 7.2 (ITS) were used.ResultsSamples were obtained at multiple time points from day 1 up to day 47 with a median of 11 samples per patient (range 2 to 17). In 11 patients all intended body regions were sampled (stool was missing in two patients and gastric secretion in two patients). The length of ICU stay and number of antibiotics administered during ICU stay was associated with loss of diversity in all investigated body sites. Taxonomic profiling showed a significant reduction of physiological members from the oral and fecal microbial community (e.g., Clostridiales, Bacteroidales, Faecalibacterium spp. etc.) after 2 weeks at the ICU. In contrast, Enterococcus spp. and Staphylococcus spp. were enriched in the gastric and fecal microbiota. Candida spp. dominated fungal communities of all body sites investigated. Staphylococcus aureus was associated with ITS positive, Candida spp. dominated samples throughout all body sites, while Pseudomonas aeruginosa was associated with ITS-negative samples.ConclusionThe length of the ICU stay and the number of different antibiotics administered during the stay at the ICU are associated with severe intestinal dysbiosis, determined by loss of physiological microbes, decreased bacterial richness and domination of low-diversity fecal microbiota. Early colonization of Candida spp. might favor a co-existance of a Staphylococcus spp.-dominated microbiota in the ICU.Disclosures All authors: No reported disclosures.

Isolation of Lactobacillus plantarum Strains With Robust Antagonistic Activity, Qualified Probiotic Properties, and Without Antibiotic-resistance From Traditional Sourdough

Background: The main purpose of the present study was to identify the qualified probiotic strains of traditional sourdough and to find stable Lactobacillus strains with enhanced antibacterial/antagonistic activity and without antibiotic resistance. Methods: Sixteen strains were isolated from traditional sourdough and their susceptibility was evaluated toward a number of different antibiotics. In addition, the isolated strains were assessed with respect to their probiotic properties, antagonistic activity, and resistance to low pH, bile salt, different NaCl concentrations, and low storage temperatures. Results: Based on the results, although none of the strains had considerable antibiotic resistance, they showed significant antagonistic activity against 6 different pathogens. Among the isolates, H3a and K3b were the most resistant to low pH and bile salt (0.3%) and demonstrated most hydrophobicity, auto-aggregation, and coaggregation characteristics. It was also observed that the strains could produce strong biofilm and were viable at 1%-10% NaCl concentrations, as well as at 4° C and -20° C. Finally, the sequencing results revealed that these 2 strains had the highest homology to Lactobacillus plantarum based on the 16S rRNA gene. Conclusions: The present data confirmed the safety of Lactobacillus content of the traditional sourdough and the unique probiotic properties of these strains.

Antibiotic resistance is lower in Staphylococcus aureus isolated from antibiotic-free raw meat as compared to conventional raw meat.

The frequent use of antibiotics contributes to antibiotic resistance in bacteria, resulting in an increase in infections that are difficult to treat. Livestock are commonly administered antibiotics in their feed, but there is current interest in raising animals that are only administered antibiotics during active infections. Staphylococcus aureus (SA) is a common pathogen of both humans and livestock raised for human consumption. SA has achieved high levels of antibiotic resistance, but the origins and locations of resistance selection are poorly understood. We determined the prevalence of SA and MRSA in conventional and antibiotic-free (AF) meat products, and also measured rates of antibiotic resistance in these isolates. We isolated SA from raw conventional turkey, chicken, beef, and pork samples and also from AF chicken and turkey samples. We found that SA contamination was common, with an overall prevalence of 22.6% (range of 2.8–30.8%) in conventional meats and 13.0% (range of 12.5–13.2%) in AF poultry meats. MRSA was isolated from 15.7% of conventional raw meats (range of 2.8–20.4%) but not from AF-free meats. The degree of antibiotic resistance in conventional poultry products was significantly higher vs AF poultry products for a number of different antibiotics, and while multi-drug resistant strains were relatively common in conventional meats none were detected in AF meats. The use of antibiotics in livestock contributes to high levels of antibiotic resistance in SA found in meat products. Our results support the use of AF conditions for livestock in order to prevent antibiotic resistance development in SA.

New molecular tools for meningitis diagnostics in Ethiopia \u2013 a necessary step towards improving antimicrobial prescription

BackgroundMeningitis remains a top cause of premature death and loss of disability-adjusted life years in low-income countries. In resource-limited settings, proper laboratory diagnostics are often scarce and knowledge about national and local epidemiology is limited. Misdiagnosis, incorrect treatment and overuse of antibiotics are potential consequences, especially for viral meningitis.MethodsA prospective study was conducted over three months in a teaching hospital in Ethiopia with limited laboratory resources. Cerebrospinal fluid (CSF) samples from patients with suspected meningitis were analysed using a multiplex PCR-based system (FilmArray, BioFire), in addition to basic routine testing with microscopy and culture. Clinical data, as well as information on treatment and outcome were collected.ResultsTwo hundred and eighteen patients were included; 117 (54%) neonates (0–29 days), 63 (29%) paediatrics (1 month-15 years) and 38 (17%) adults (≥16 years). Of 218 CSF samples, 21 (10%) were PCR positive; 4% in neonates, 14% in paediatrics and 18% in adults. Virus was detected in 57% of the PCR positive samples, bacteria in 33% and fungi in 10%. All CSF samples that were PCR positive for a bacterial agent had a white cell count ≥75 cells/mm3 and/or turbid appearance. The majority (90%) of patients received more than one antibiotic for treatment of the meningitis episode. There was no difference in the mean number of different antibiotics received or in the cumulative number of days with antibiotic treatment between patients with a microorganism detected in CSF and those without.ConclusionsA rapid molecular diagnostic system was successfully implemented in an Ethiopian setting without previous experience of molecular diagnostics. Viral meningitis was diagnosed for the first time in routine clinical practice in Ethiopia, and viral agents were the most commonly detected microorganisms in CSF. This study illustrates the potential of rapid diagnostic tests for reducing antibiotic usage in suspected meningitis cases. However, the cost of consumables for the molecular diagnostic system used in this study limits its use in low-income countries.

Implementation of an Antibiotic Therapy Protocol for Open Fractures in the Emergency Department

CONTEXTWell established in the Emergency Department (ED) literature is that the most important factor in decreasing subsequent infection rate in open fractures is the time to first administration of antibiotics. As such, the authors developed a new ED open fracture antibiotic protocol to facilitate more expeditious antibiotic administration and appropriate choice of antibiotics.METHODSDuring Phase 1 of this project, the authors identified the 2012 - 2016 historical length of time from presentation of an open fracture to the possible initiation of antibiotic therapy at their institution. Results demonstrated critical areas for improvement in both timing and types of antibiotics administered. Phase 2 of the study evaluated the effect of the new open fracture antibiotic protocol. Sample cases from both phases were then further identified based on type of open fracture, time to initiation of antibiotics from ED presentation, type of antibiotics, and time to definitive treatment. Analyses were performed using GraphPad proprietary software.RESULTSA random sample of 110 patients were included from Phase 1 and 27 patients from Phase 2. A total of 43 Phase 1 patients were administered cefazolin (Kefzol, Ancef); the remainder of the patients received a number of different antibiotics. During Phase 2, all 27 patients received cefazolin and Gentamycin if necessary per the new protocol. The average time to initiation of antibiotics was 0.907 hours during Phase 1 compared to 0.568 hours in Phase 2. The new protocol also significantly decreased the average time to antibiotics in ED from 2.17 hours to 1.82 hours when including EMS transfer time. Average time to definitive treatment in the operating room was 6.63 hours during Phase 1 and was significantly lowered to 3.97 hours during Phase 2.CONCLUSIONSTiming to initiation of antibiotics after open fractures is the most important aspect to decrease infection rates. In order to decrease these times, the authors implemented a new ED protocol that specifically stated the type of antibiotic to be given based on the open fracture without orthopedics needing to be notified before administration. Ideally, the use of such protocols in ED settings will serve to greatly decrease infection risks after open fracture.

Occurrence of tetracyclines and sulfonamides in manures, agricultural soils and crops from different areas in Galicia (NW Spain)

Abstract Antibiotics released to the environment are causing public health and sustainability concerns. Taking that into account, we studied the presence of tetracyclines (Tetracycline, Oxytetracycline, Chlortetracycline and Doxycycline) and sulfonamides (Sulfadiazine, Sulfamethazine, Sulfachlorpyridazine and Sulfamethoxypyridazine) in manures, soils and crops from Galicia (Spain), where a high number of cattle, pig and poultry farms exist. We used the HPLC-MS/MS technique to analyze 40 samples of cattle, pig and poultry manure, as well as 65 soil samples, and 27 vegetation samples. The presence of antibiotics was detected in 42% of the manures, 17% of the soils and 44% of crop samples, with maximum concentrations of 106.0 mg kg−1 for individual antibiotics in manures and 0.6 mg kg−1 in soils and plants. The simultaneous presence of several antibiotics was infrequent in soils (only three soils presented two or three antibiotics), and more common in manures and plants, some of them with up to five antibiotics. Pig slurries showed the highest antibiotic concentrations, as well as the highest number of different antibiotics. Crops fertilized with these slurries also showed the highest number of different antibiotics. Antibiotics were detected in 71% of grass and corn samples, and in 33% of wheat grain samples, while they were not detected in potato samples. These results can be very relevant taking into account potential environmental and public health repercussions of antibiotics in soil and water, as well as antibiotics uptake and accumulation in plants, and subsequent incorporation to the food chain.

Medical and surgical management of intraspecific wounds in a European beaver kit (Castor fiber)

A captive European beaver (Castor fiber) kit, of approximately eight to ten weeks of age, was found in his enclosure with multiple wounds caused by intraspecific aggression. Six wounds healed quickly, while three progressed to abscessation. Severe proprioceptive deficits developed in both hindlegs as a secondary complication. A number of different antibiotics, general anaesthesia and basic physiotherapy (including range‐of‐motion exercises and hydrotherapy) were used in conjunction to treat these wounds over the following 10 months. Anti‐inflammatories were used as needed. Bacteria cultured from the infected wounds included Enterobacter cloacae, Serratia marcescens, Klebsiella pneumoniae, Pseudomonas aeruginosa, Serratia liquefaciens and Stenotrophomonas maltophilia. This report presents previously unreported information regarding the use and effectiveness of various medications and physiotherapy techniques in juvenile European beavers.

Clinical teaching skills for midwives

Sixty-eight hospital-admitted patients with a first episode of Clostridium difficile infection (CDI) were included and followed up during 1 year. Faeces samples were collected at 1, 2, 6 and 12 months after inclusion and analyzed for the presence of C. difficile toxin B, genes for toxin A, toxin B, binary toxin and TcdC deletion by PCR. All strains were also PCR-ribotyped and the MICs of the isolates were determined against eight antimicrobial agents. In 68 patients initially included, antibiotics, clinical signs and co-morbidities were analyzed and 56 were evaluable for recurrences. The mean number of different antibiotics given during 3 months prior to inclusion was 2.6 (range 0–6). Six patients had not received any antibiotics and three of them had diagnosed inflammatory bowel disease. Thirty-two patients (57%) had either a microbiological or clinical recurrence, 16 of whom had clinical recurrences that were confirmed microbiologically (13, 23%) or unconfirmed by culture (3, 5%). Twenty-nine patients were positive in at least one of the follow-up tests, 16 had the same ribotype in follow-up tests, i.e. relapse, and 13 a different ribotype, i.e., reinfection. Most common ribotypes were 078/126, 020, 023, 026, 014/077, 001 and 005. No strain of ribotype 027 was found. Strains ribotype 078/126 and 023 were positive for binary toxin and were the strains most prone to cause recurrence. All strains were sensitive to vancomycin and metronidazole. Patients with recurrences were significantly older (p = 0.02) and all patients had a high burden of comorbidities, which could explain the high fatality rate, 26 (38%) patients died during the 1-year follow-up.

Clostridium difficile recurrences in Stockholm

Sixty-eight hospital-admitted patients with a first episode of Clostridium difficile infection (CDI) were included and followed up during 1 year. Faeces samples were collected at 1, 2, 6 and 12 months after inclusion and analyzed for the presence of C. difficile toxin B, genes for toxin A, toxin B, binary toxin and TcdC deletion by PCR. All strains were also PCR-ribotyped and the MICs of the isolates were determined against eight antimicrobial agents. In 68 patients initially included, antibiotics, clinical signs and co-morbidities were analyzed and 56 were evaluable for recurrences. The mean number of different antibiotics given during 3 months prior to inclusion was 2.6 (range 0–6). Six patients had not received any antibiotics and three of them had diagnosed inflammatory bowel disease. Thirty-two patients (57%) had either a microbiological or clinical recurrence, 16 of whom had clinical recurrences that were confirmed microbiologically (13, 23%) or unconfirmed by culture (3, 5%). Twenty-nine patients were positive in at least one of the follow-up tests, 16 had the same ribotype in follow-up tests, i.e. relapse, and 13 a different ribotype, i.e., reinfection. Most common ribotypes were 078/126, 020, 023, 026, 014/077, 001 and 005. No strain of ribotype 027 was found. Strains ribotype 078/126 and 023 were positive for binary toxin and were the strains most prone to cause recurrence. All strains were sensitive to vancomycin and metronidazole. Patients with recurrences were significantly older (p = 0.02) and all patients had a high burden of comorbidities, which could explain the high fatality rate, 26 (38%) patients died during the 1-year follow-up.

A prospective study of community-associated Clostridium difficile infections: The role of antibiotics and co-infections

This prospective study was performed to determine the incidence, risk factors, severity and outcomes of community-associated Clostridium difficile infection (CA-CDI) in the SE of Scotland. All patients (335) diagnosed with laboratory confirmed CDI in the city of Edinburgh, East Lothian and Midlothian regions of Scotland between August 2010 and July 2011 were followed up for one year after diagnosis. Clinical details and laboratory markers were recorded. Stool samples were tested for C. difficile, other bacterial pathogens and norovirus. Molecular epidemiology of C. difficile isolates was studied by PCR-ribotyping. Of the total 335 confirmed CDI cases, PCR-ribotype 001 was the commonest (14.1%), followed by PCR-ribotypes 078 (12.9%) and 015 (11.7%), respectively. CA-CDI represented 12.5% of the cases. In these, PCR-ribotype 078 was the commonest (19.0%), followed by PCR-ribotypes 014/020 (16.7%), PCR-ribotype 015 (14.3% and PCR-ribotype 001 (11.9%). A lower Charlson co-morbidity index and a lower age was observed in the CA-CDI group as was total number of different antibiotic classes whereas age >75 was more common in the HA-CDI group. On multivariable analysis presence of PCR-ribotype 078 was significantly associated with community acquisition (p = 0.006) whereas a greater proportion of immunosuppressed patients and those on antibiotics 8 weeks preceding diagnosis (p = 0.035 and p = 0.005 respectively) were found among HA-CDI cases. Charlson co-morbidity index, number of different antibiotics given in the eight weeks preceding onset, severity of infection and rural residence were not significantly different between the two groups. This study demonstrates that patients with CA-CDI may also present with severe infection, are less likely to receive antibiotics prior to CDI, more likely to be younger in age and have a greater proportion of PCR-ribotype 078 compared with CDI acquired in a hospital setting. Hence a high level of vigilance must be maintained to detect CDI cases which present in the community without the traditional predisposing factors.

An examination of the inhibitory effects of three antibiotics in combination on ribosome biosynthesis in Staphylococcus aureus

Although a number of different antibiotics are used to combat staphylococcal infections, resistance has continued to develop. The use of rifampicin and ciprofloxacin in combination with azithromycin, known for its inhibitory effects on the bacterial ribosome, can create potential synergistic effects on ribosomal subunit synthesis rates. In this work, combination antibiotic treatments gave a significant decrease in cell numbers following growth in the presence of ciprofloxacin or rifampicin with azithromycin compared to those grown with azithromycin or rifampicin alone. DNA, RNA and protein synthesis rates were reduced with single antibiotic treatments and showed further decreases when drug combinations were used. 70S ribosome levels were reduced with every antibiotic treatment. DNA gyrase subunits A and B showed significant decreases for double and triple antibiotic-treated samples. Ribosomal subunit synthesis rates were diminished for each different antibiotic combination. Turnover of 16S and 23S rRNA was also observed in each case and was stimulated by antibiotic combinations. The frequency of spontaneous resistance was reduced in all double selections, and no triply resistant mutants were found.

Monitoring bacterial resistance to chloramphenicol and other antibiotics by liquid chromatography electrospray ionization tandem mass spectrometry using selected reaction monitoring

Antibiotic resistance is a growing problem worldwide. For this reason, clinical laboratories often determine the susceptibility of the bacterial isolate to a number of different antibiotics in order to establish the most effective antibiotic for treatment. Unfortunately, current susceptibility assays are time consuming. Antibiotic resistance often involves the chemical modification of an antibiotic to an inactive form by an enzyme expressed by the bacterium. Selected reaction monitoring (SRM) has the ability to quickly monitor and identify these chemical changes in an unprecedented time scale. In this work, we used SRM as a technique to determine the susceptibility of several different antibiotics to the chemically modifying enzymes β-lactamase and chloramphenicol acetyltransferase, enzymes used by bacteria to confer resistance to major classes of commonly used antibiotics. We also used this technique to directly monitor the effects of resistant bacteria grown in a broth containing a specific antibiotic. Because SRM is highly selective and can also identify chemical changes in a multitude of antibiotics in a single assay, SRM has the ability to detect organisms that are resistant to multiple antibiotics in a single assay. For these reasons, the use of SRM greatly reduces the time it takes to determine the susceptibility or resistance of an organism to a multitude of antibiotics by eliminating the time-consuming process found in other currently used methods.

Inhibition of Ribosomal Subunit Synthesis in Escherichia coli by the Vanadyl Ribonucleoside Complex

The increase in antibiotic-resistant microorganisms has driven a search for new antibiotic targets and novel antimicrobial agents. A large number of different antibiotics target bacterial ribosomal subunit formation. Several specific ribonucleases are important in the processing of rRNA during subunit biogenesis. This work demonstrates that the ribonuclease inhibitor, vanadyl ribonucleoside complex (VRC), can inhibit RNases involved in ribosomal subunit formation. The ribosomal subunit synthesis rate was significantly decreased and ribosomal RNA from the subunit precursors was degraded. VRC had no inhibitory effect on translation. VRC also potentiated the inhibitory effects of an aminoglycoside and a macrolide antibiotic.