History Of Antibiotic Exposure Research Articles

Investigation of antimicrobial susceptibility patterns, risk factors and their impact on mortality in cancer patients at a tertiary care cancer hospital- A prospective study

BackgroundCancer patients are vulnerable to infections due to immunosuppression caused by cancer itself and its treatment. The emergence of antimicrobial-resistant bacteria further complicates the treatment of infections and increases the mortality and hospital stays. This study aimed to investigate the microbial spectrum, antimicrobial resistance patterns, risk factors, and their impact on clinical outcomes in these patients.MethodsA prospective study was conducted at a tertiary care cancer hospital in Patna, Bihar, India, which included cancer patients aged 18 years and older with positive microbial cultures.ResultsThis study analysed 440 patients, 53% (234) of whom were females, with an average age of 49.27 (± 14.73) years. A total of 541 isolates were identified, among which 48.01% (242) were multidrug resistant (MDR), 29.76% (150) were extensively drug resistant (XDR), and 19.84% (112) were sensitive. This study revealed that patients who underwent surgery, chemotherapy, were hospitalized, had a history of antibiotic exposure, and had severe neutropenia were more susceptible to MDR and XDR infections. The average hospital stays were 16.90 (± 10.23), 18.30 (± 11.14), and 22.83 (± 13.22) days for patients with sensitive, MDR, and XDR infections, respectively. The study also revealed overall 30-day mortality rate of 31.81% (140), whereas the MDR and XDR group exhibited 38.92% and 50.29% rates of 30-day mortality respectively (P < 0.001). Possible risk factors identified that could lead to mortality, were cancer recurrence, sepsis, chemotherapy, indwelling invasive devices such as foley catheter, Central venous catheter and ryles tube, MASCC score (< 21) and pneumonia.ConclusionsThis study emphasizes the necessity for personalized interventions among cancer patients, such as identifying patients at risk of infection, judicious antibiotic use, infection control measures, and the implementation of antimicrobial stewardship programs to reduce the rate of antimicrobial-resistant infection and associated mortality and hospital length of stay.

High Prevalence of Colistin-Resistant Encoding Genes Carriage among Patients and Healthy Residents in Vietnam.

Background and Objectives: We aimed to investigate the carriage of colistin-resistant genes among both patients with a history of antibiotic exposure and apparently healthy adults with no recent healthcare contact. Materials and Methods: Stool swabs were collected from healthy people, and specimens were collected at the infection foci from the patients. Eleven primer/probe sets were used to perform the Multiplex Real-Time PCR assay with the QuantiNova Multiplex Probe PCR kit for screening the carriage of colistin-resistant genes (mcr-1 to mcr-10) and 16S rRNA gene as internal control. Results: In total, 86 patients and 96 healthy residents were included. Twenty two patients (25.9%) were positive with at least one colistin-resistance encoding gene. The mcr-1 gene was the most frequent (16.5%), followed by mcr-9, mcr-6, and mcr-4 genes, where the prevalence was 11.8%, 10.6%, and 9.4%, respectively. No patient was positive with mcr-3, mcr-7, and mcr-8 genes. Eight patients (9.4%) were positive with multiple colistin-encoding genes. Twenty-three healthy people (24.0%) were positive with at least one colistin-resistance encoding gene, and the mcr-10 gene was the most frequent (27.0%), followed by the mcr-1, mcr-8, and mcr-9 genes, where the prevalence was 24.3%, 21.6%, and 13.5%, respectively. No person was positive with the mcr-2 and mcr-5 genes. Conclusions: Our findings underscore the urgent need for enhanced surveillance, infection control measures, and stewardship interventions to mitigate the spread of colistin resistance in Vietnam.

Exploring Prior Antibiotic Exposure Characteristics for COVID-19 Hospital Admission Patients: OpenSAFELY.

Previous studies have demonstrated the association between antibiotic use and severe COVID-19 outcomes. This study aimed to explore detailed antibiotic exposure characteristics among COVID-19 patients. Using the OpenSAFELY platform, which integrates extensive health data and covers 40% of the population in England, the study analysed 3.16 million COVID-19 patients with at least two prior antibiotic prescriptions. These patients were compared to up to six matched controls without hospitalisation records. A machine learning model categorised patients into ten groups based on their antibiotic exposure history over the three years before their COVID-19 diagnosis. The study found that for COVID-19 patients, the total number of prior antibiotic prescriptions, diversity of antibiotic types, broad-spectrum antibiotic prescriptions, time between first and last antibiotics, and recent antibiotic use were associated with an increased risk of severe COVID-19 outcomes. Patients in the highest decile of antibiotic exposure had an adjusted odds ratio of 4.8 for severe outcomes compared to those in the lowest decile. These findings suggest a potential link between extensive antibiotic use and the risk of severe COVID-19. This highlights the need for more judicious antibiotic prescribing in primary care, primarily for patients with higher risks of infection-related complications, which may better offset the potential adverse effects of repeated antibiotic use.

High fat intake sustains sorbitol intolerance after antibiotic-mediated Clostridia depletion from the gut microbiota

Carbohydrate intolerance, commonly linked to the consumption of lactose, fructose, or sorbitol, affects up to 30% of the population in high-income countries. Although sorbitol intolerance is attributed to malabsorption, the underlying mechanism remains unresolved. Here, we show that a history of antibiotic exposure combined with high fat intake triggered long-lasting sorbitol intolerance in mice by reducing Clostridia abundance, which impaired microbial sorbitol catabolism. The restoration of sorbitol catabolism by inoculation with probiotic Escherichia coli protected mice against sorbitol intolerance but did not restore Clostridia abundance. Inoculation with the butyrate producer Anaerostipes caccae restored a normal Clostridia abundance, which protected mice against sorbitol-induced diarrhea even when the probiotic was cleared. Butyrate restored Clostridia abundance by stimulating epithelial peroxisome proliferator-activated receptor-gamma (PPAR-γ) signaling to restore epithelial hypoxia in the colon. Collectively, these mechanistic insights identify microbial sorbitol catabolism as a potential target for approaches for the diagnosis, treatment, and prevention of sorbitol intolerance.

Characteristics of non-carbapenemase producing carbapenem-resistant Klebsiella pneumoniae from a tertiary hospital in China.

The spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a substantial severe global public health burden. Non-carbapenemase-producing CRKP (non-CP-CRKP) is increasingly recognized as the source of severe infections. We analyzed the genotypic, and phenotypic profiles of non-CP-CRKP strains with the whole-genome sequences isolated between 2017 and 2019 and the clinical characterization of non-CP-CRKP infection. A total of 91 CRKP strains were collected, of which 5 (5.49%) strains were non-CP-CRKP. Four strains were from male patients; three strains were isolated from the bile of patients who underwent biliary interventional surgery and four had a history of antibiotic exposure. Three strains were sequence type (ST)11, one was ST1, and one was ST5523. The non-CP-CRKP strains were insusceptible to ertapenem. Three strains were susceptible to amikacin. All the strains were susceptible to imipenem, meropenem, tigecycline, ceftazidime/avibatam and polymyxin B. The β-lactamases of non-CP-CRKP predominantly included blaCTX-M, blaSHV, and blaTEM subtypes. Two site mutations in ompK36 (p.A217S and p.N218H) and four in ompK37 (p.I70M, p.I128M, p.N230G, and m233_None234insQ) were detected accounting for carbapenem resistance. Plasmids IncFI and IncFII were found in most strains. Genes encoding aerobactin, yersiniabactin and allantoin utilization were not detected in several isolates, and all non-CP-CRKP strains did not carry rmpA gene. Non-CP-CRKP infected patients had a history of previous antibiotic exposure or invasive procedures. Non-CP-CRKP strains were insusceptible to ertapenem. The mechanism of resistance includes β-lactamases production and the site mutations in ompK36 and ompK37. Several virulence genes were not detected in non-CP-CRKP.

Genomic Insights into Virulence Factors and Multi-Drug Resistance in Clostridium perfringens IRMC2505A.

Clostridium perfringens is a spore-forming, Gram-positive anaerobic pathogen that causes several disorders in humans and animals. A multidrug-resistant Clostridium strain was isolated from the fecal sample of a patient who was clinically suspected of gastrointestinal infection and had a recent history of antibiotic exposure and diarrhea. The strain was identified by 16s rRNA sequencing as Clostridium perfringens. The strain's pathogenesis was analyzed through its complete genome, specifically antimicrobial resistance-related genes. The Clostridium perfringens IRMC2505A genome contains 19 (Alr, Ddl, dxr, EF-G, EF-Tu, folA, Dfr, folP, gyrA, gyrB, Iso-tRNA, kasA, MurA, rho, rpoB, rpoC, S10p, and S12p) antibiotic-susceptible genetic species according to the k-mer-based detection of antimicrobial resistance genes. Genome mapping using CARD and VFDB databases revealed significant (p-value = 1 × 10-26) genes with aligned reads against antibiotic-resistant genes or virulence factors, including phospholipase C, perfringolysin O, collagenase, hyaluronidase, alpha-clostripain, exo-alpha-sialidase, and sialidase activity. In conclusion, this is the first report on C. perfringens from Saudi Arabia that conducted whole genome sequencing of IRMC2505A and confirmed the strain as an MDR bacterium with several virulence factors. Developing control strategies requires a detailed understanding of the epidemiology of C. perfringens, its virulence factors, and regional antimicrobial resistance patterns.

Bacterial Co-Infection and Empirical Antibacterial Therapy in Patients With COVID-19.

The rate and composition of bacterial co-infection in patients with coronavirus disease 2019 (COVID-19) were evaluated when microbiological testing was conducted on the majority of patients. We also evaluated whether the use of empirical antibacterials was associated with mortality. In this retrospective study, all of the adult patients with COVID-19 hospitalized in a single tertiary hospital in South Korea between February 2020 and December 2021 were included. Bacterial co-infection was assessed by sputum cultures, blood cultures, and molecular testing, including polymerase chain reaction sputum testing and urinary antigen tests. Mortality was compared between patients who received empirical antibacterials and those who did not. Of the 367 adult patients admitted during the study period, 300 (81.7%) had sputum culture results and were included in the analysis. Of these 300 patients, 127 (42.3%) had a history of antibiotic exposure. The co-infection rate within 48 hours was 8.3% (25/300): 6.4% (11/173) of patients without prior antibiotic exposure and 11% (14/127) of patients with prior antibacterial exposure. The co-infected bacteria were different according to antibacterial exposure before admission, and multi-drug resistant pathogens were detected exclusively in the antibacterial exposed group. Among the patients without positive results for the microbiological tests, empirical antibacterials were used in 33.3% of cases (100/300). Empirical antibacterial therapy was not significantly related to the 30-day mortality or in-hospital mortality rates in the study cohort before or after the propensity score-matching. In this study including only patients underwent microbiological testing, bacterial co-infection was not frequent, and the co-infected organisms varied depending on previous antibacterial exposures. Given the rarity of co-infection and the lack of potential benefits, empiric antibacterial use in COVID-19 should be an important target of antibiotic stewardship.

785. Bacterial Co-infection and Empirical Antibiotic Therapy in Patients with COVID-19

Abstract Background Understanding the rate and composition of bacterial co-infection is important to determine antibiotic therapy in SARS-CoV-2 infection, but those vary according to healthcare settings and regional differences. We evaluated the rate of bacterial co-infection in hospitalized patients with COVID-19 in a single tertiary hospital in South Korea. Methods In this retrospective study, all the adult patients with COVID-19 hospitalized between Feb 2020 and Dec 2021 were included. Bacterial co-infection rate was assessed by results of sputum cultures, blood cultures, pneumococcal urinary antigen, Legionella urinary antigen, sputum Legionella pneumophilia PCR, and sputum multiplex PCR for Mycoplasma pneumoniae and Chlamydia pneumoniae. Characteristics and outcomes of patients were evaluated according to antibiotics exposure prior to hospitalization. Results Of 367 adult patients, 300 (81.7%) patients having sputum culture results were included in the analysis. Of these, 127 (42.3%) had a history of antibiotic exposure within 1 month before hospitalization. The coinfection rate within 48 hours of hospitalization was confirmed in 8.3% (25/300): 6.4% (11/163) of patients without prior antibiotic exposure and 11% (14/127) of patients with prior antibiotic exposure. In the group without prior antibiotic exposure, pathogens responsible for community-onset infections were isolated, whereas nosocomial pathogens were predominantly isolated in the antibiotic-exposed group. Empirical antibiotics were used in 144 (66%) of 275 patients without positive results for microbiological tests. Empirical antibiotic use in patients without positive results for microbiological tests was not significantly associated with 30-day mortality or in-hospital mortality after adjusting covariates including age, sex, comorbidity, anti-inflammatory treatment, and COVID-19 severity. Conclusion In this study with a high rate of microbiological testing, bacterial co-infection was not frequent, and the results varied depended on previous exposure to antibiotics. Given the rarity of bacterial co-infection and the lack of potential benefits of empirical antibiotic therapy, the antibiotic use in patients with COVID-19 should be restricted as an important target of antibiotic stewardship. Disclosures All Authors: No reported disclosures.

Prevalence and risk factors of carbapenem-resistant Enterobacterales positivity by active screening in intensive care units in the Henan Province of China: A multi-center cross-sectional study.

ObjectiveIn intensive care units (ICUs), carbapenem-resistant Enterobacterales (CRE) pose a significant threat. We aimed to examine the distribution, epidemiological characteristics, and risk factors for CRE positivity in ICUs.Materials and methodsThis cross-sectional study was conducted in 96 ICUs of 78 hospitals in Henan Province, China. The clinical and microbiological data were collected. A multivariable logistic regression model was used to analyze the risk factors for CRE positivity.ResultsA total of 1,009 patients were enrolled. There was a significant difference in CRE positive rate between pharyngeal and anal swabs (15.16 vs. 19.13%, P < 0.001). A total of 297 carbapenem-resistant Klebsiella pneumoniae (CR-KPN), 22 carbapenem-resistant Escherichia coli (CR-ECO), 6 carbapenem-resistant Enterobacter cloacae (CR-ECL), 19 CR-KPN/CR-ECO, and 2 CR-KPN/CR-ECL were detected. Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), and a combination of KPC and NDM were detected in 150, 9, and 11 swab samples, respectively. Multivariable logistic regression analysis determined length of ICU stay, chronic neurological disease, transfer from other hospitals, previous infection, and history of antibiotics exposure as independent risk factors for CRE positivity. Age and cardiovascular diseases were independent risk factors for mixed infections of CRE. The occurrence of CRE in secondary and tertiary hospitals was 15.06 and 25.62%, respectively (P < 0.05). Patients from tertiary hospitals had different clinical features compared with those from secondary hospitals, including longer hospital stays, a higher rate of patients transferred from other hospitals, receiving renal replacement therapy, exposure to immunosuppressive drugs, use of antibiotics, and a higher rate of the previous infection.ConclusionIn ICUs in Henan Province, CRE positive rate was very high, mostly KPC-type CR-KPN. Patients with prolonged ICU stay, chronic neurological disease, transfer from other hospitals, previous infection, and history of antibiotic exposure are prone to CRE. Age and cardiovascular diseases are susceptibility factors for mixed infections of CRE. The CRE positive rate in tertiary hospitals was higher than that in secondary hospitals, which may be related to the source of patients, antibiotic exposure, disease severity, and previous infection.

Comparable Results of Helicobacter pylori Antibiotic Resistance Testing of Stools vs Gastric Biopsies Using Next-Generation Sequencing

Comparable Results of Helicobacter pylori Antibiotic Resistance Testing of Stools vs Gastric Biopsies Using Next-Generation Sequencing

Comparison of the dynamic responses of different anammox granules to copper nanoparticle stress: Antibiotic exposure history made a difference

Two types of anaerobic ammonium oxidation (anammox) seed sludge were selected to evaluate their responses to copper nanoparticles (CuNPs) exposure. Antibiotic-exposed anammox granules (R1) were more likely to be inhibited by 5.0 mg L-1 CuNPs than the normal anammox granules (C1). The nitrogen removal efficiency (NRE) of C1 decreased by 9.00% after two weeks of exposure to CuNPs, whereas that of R1 decreased by 20.32%. Simultaneously, the abundance of Candidatus. Kuenenia decreased by 27.65% and 36.02% in C1 and R1 under CuNPs stress conditions, respectively. Generally, R1 was more susceptible to CuNPs than C1. The correlation analysis indicated that the horizontal transfer of antibiotic resistance genes and copA triggered by intI1 facilitated the generation of multiresistance in the anammox process. Moreover, the potential multiresistance mechanism of anammox bacteria was hypothesized based on previous results. The results will generate new ideas for the treatment of complex wastewater using the anammox process.

#41: Examining the Role of Rurality on the Incidence of Acute Respiratory Illnesses, Overall Antibiotic Use and Inappropriate Antibiotic Use Among Young Children in Tennessee

Abstract Background The Centers for Disease Control and Prevention (CDC) defines inappropriate antibiotic use as prescribing antibiotics not in accordance with national and local evidence-based guidelines, wrong selection of antibiotics, wrong dosing of antibiotics, or wrong duration of antibiotic use. Inappropriate antibiotic use has been associated with the development and transmission of antibiotic-resistant organisms. Acute respiratory illnesses (ARI) are the leading causes of antibiotic use among children with rates of antibiotic use in Tennessee children among the highest in the United States. The reasons for this have not been adequately assessed, particularly in children enrolled in the Tennessee Medicaid (TennCare) program, who tend to live in low-income households and rural locales and are disproportionately underrepresented in database studies conducted in large managed care organizations. We sought to examine whether the rates of ARI-related overall antibiotic use and inappropriate antibiotic use among young children enrolled in TennCare vary by the rurality of their county of residence. Methods This was a retrospective cohort study of children aged 2 months–5 years enrolled in TennCare from July 1, 2007, to June 30, 2017. We used pharmacy and healthcare claims data to calculate the incidence of ARI and ARI-related antibiotic use. Each eligible child entered into the cohort at the earliest time when selection criteria were met, and follow-up continued from cohort entry until the earliest of loss of enrollment, death, end of study, or meeting exclusion criteria. ARI was identified using International Classification of Diseases, Ninth and Tenth Revisions (ICD-9 and ICD-10) and ARI-related antibiotic use was defined as an antibiotic prescription filled within 72 hours of an ARI. ARI-related antibiotic use was classified as potentially appropriate or inappropriate using a previously published CDC classification system. The rurality of children’s county of residence was defined as either mostly urban, mostly rural, or completely rural based upon the United States Census Bureau definitions. We calculated incidence rates for ARI, ARI-related antibiotic use, and ARI-related inappropriate antibiotic use. To assess the effect of rurality of residence on these outcomes, we used multivariable mixed-effects Poisson regression. These analyses accounted for other factors including child age, gender, race, underlying comorbidities, calendar year and month, and history of antibiotic exposure. Results In total, 813,432 children met enrollment criteria and contributed a total of 2,057,272 person-years for the cohort. Overall, the rate of ARIs, antibiotic use associated with ARIs, and inappropriate antibiotic use associated with ARIs has trended down over time (Figure 1A). There were higher rates of these three outcomes in children who live in mostly rural and completely rural counties compared with those who live in mostly urban counties (Figure 1B–D). Conclusions Children who live in rural counties in Tennessee are disproportionately affected by higher rates of ARIs, antibiotic use, and inappropriate antibiotic use compared with those who live in urban counties. These findings can inform targeted stewardship interventions to reduce inappropriate antibiotic prescribing and to decrease the rates of antibiotic-resistant infections.

Epidemiology of NDM-Producing Enterobacteriaceae in Michigan

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are classified as an urgent antibiotic-resistant threat by the CDC, and they are listed on the critical priority list by the World Health Organization due to the lack of antibiotic treatment options. New-Delhi metallo-β-lactamase (NDM) is an emerging mechanism of carbapenem resistance in the United States. We sought to understand the risk factors and clinical characteristics of patients with NDM CRE in Michigan to improve surveillance. Methods:A retrospective descriptive study was conducted in collaboration with the Michigan Department of Health and Human Services (MDHHS). CRE isolates submitted to MDHHS between April 2014 and July 2019 were tested for the presence of NDM using CDC PCR protocols. Additional information on case demographics, laboratory results, healthcare and antibiotic exposure history, and travel history were collected. Results: In total, 30 NDM cases were identified in Michigan during the study period. Of these 30 cases, 15 (50%) were men, and the median age was 73.5 years (range, 20–88 20). Also, 2 of these patients (6.6%) were immunocompromised; 2 patients (6.6%) had had extensive abdominal surgery, and 2 patients (6.6%) had recurrent hospitalization. Furthermore, 12 case isolates (40%) were collected in outpatient settings, whereas 16 (53%) were collected from inpatient settings. In addition, 13 (43%) patients were admitted from home and 4 (13%) presented from an extended-care facility. Urine was the most common site of isolation in 19 of 30 (63%) cases, followed by blood and tissue culture in 4 of 30 (13%) each. Escherichia coli was the most common organism (17 of 30, 57%), followed by Klebsiella pneumoniae (9 of 30, 30%). Also, 15 of 30 cases (50%) had a recent history of international travel, and of these, 9 of 15 (60%) reported travel to India. Among these 15 cases, 12 (80%) sought medical care in the countries they visited. Two cases (6.6%) had a documented history of multidrug-resistant organism colonization or infection. The mortality rate was 6.6% (2 of 30). The mean time from admission to implementation of contact precautions was 7.3 days (range, 0–20). Conclusions: Suspicion of NDM CRE strains should remain high in patients with a travel history from areas known as major reservoirs of NDM. Delay in implementing contact precautions, as noted in the present study, can lead to a greater risk of transmission. Early detection and subsequent isolation of NDM patients are essential strategies for preventing transmission within healthcare facilities. Future efforts include performing whole-genome sequencing of these isolates to assist in identifying potential epidemiological links among the affected patients.Funding: NoneDisclosures: None

Analysis of the Primary and Post-Treatment Antibiotic Resistance of Helicobacter pylori in the Nanjing Area

Resistance of Helicobacter pylori (H. pylori) to antibiotics is increasing worldwide. The study was aimed to understand the current situation of antibiotic resistance in Nanjing and to provide a reasonable basis for clinical selection of antibiotics to cure H. pylori. To investigate the current status of H. pylori antibiotics resistance in the Nanjing area, and analyze the primary and post-treatment antibiotic resistance of H. pylori in this area. During the period from July 2017 to December 2019, 1533 gastric mucosal specimens from patients with positive H. pylori confirmed by a breath test or rapid urease test were collected for isolation and identification of H. pylori. The agar dilution method was used for the antibiotic resistance test. The result showed that the resistance rates of H. pylori to amoxicillin, clarithromycin, levofloxacin, furazolidone, tetracycline and metronidazole were 2.74%, 47.03%, 33.59%, 0.91%, 0.52% and 80.76%, respectively in the period of July 2017 to December 2019. The resistance rates of H. pylori (primary vs. post-treatment) to amoxicillin, clarithromycin, levofloxacin, furazolidone, tetracycline and metronidazole were 1.83% vs. 6.08%, 38.62% vs. 77.81%, 27.41% vs. 56.23%, 0.58% vs. 2.13%, 0.33% vs. 1.22%, 78.57% vs. 88.75%, respectively. Antibiotic resistance of H. pylori remained a problem for the effective eradication of this pathogen and its associated diseases in the Nanjing area. For post-treatment eradication patients, clinicians should take into account regional antibiotic resistance rate, personal antibiotic exposure history, economic benefit ratio, adverse antibiotic reactions, antibiotic availability and other aspects.

Infection rate and clinical characteristics of toxigenic Clostridium difficile in children with inflammatory bowel disease

Objective: To explore the infection rate and clinical characteristics of toxigenic Clostridium difficile in children with inflammatory bowel disease (IBD). Methods: From July 2015 to October 2016, the fecal samples and clinical data of 30 IBD children admitted to Department of Gastroenterology, Beijing Children's Hospital, Capital Medical University, as well as the specimens and data of 30 healthy children were collected in the meantime. The toxin gene of Clostridium difficile was detected and clinical characteristics of children with positive toxin gene were analyzed retrospectively. χ(2) test was used to compare the variables between groups. Results: Among the 30 IBD patients, 15 were in ulcerative colitis (UC) group and 15 in Crohn's disease (CD) group. In the IBD group, 6 (3 in UC and 3 in CD group) had positive result of toxigenic Clostridium difficile (20%), among whom 5 were toxin Clostridium difficile A (tcdA) +toxin Clostridium difficile B (tcdB) -, and 1 was tcdA+tcdB+. In the healthy group, only one had positive result of toxigenic Clostridium difficile (3%), which was tcdA+tcdB-. Binary toxin gene was negative in both groups. The infection rate of toxigenic Clostridium difficile in IBD group was significantly higher than that in healthy control group (χ(2)=4.043, P=0.044). In UC group, no Clostridium difficile toxin gene was detected during the remission period (0/1), one case was positive for toxin gene (1/11) during mild active period, and 2 cases were (2/3) during moderately active period. There were significant differences in the infection rate of toxigenic Clostridium difficile between patients in different active period (χ(2)=4.000, P=0.046). The main manifestations of the 6 cases were diarrhea, abdominal pain and bloody stool, and the relapsed case was characterized by sudden aggravation. TcdA was detected in all toxin gene positive samples, and 1 case combined with tcdB had more serious bloody mucopurulent stool. Five cases had colonoscopy, but there was no obvious characteristics of toxigenic Clostridium difficile colitis such as yellow white plaques or pseudomembranous spot. Three cases had antibiotic exposure history. All 6 cases were sensitive to metronidazole treatment, and stable without relapse during the 3-month follow-up. Conclusions: The infection rate of toxigenic Clostridium difficile in children with IBD is higher than that in healthy children. The patients with both tcdA and tcdB could have more serious clinical symptoms, although there may not be specific pathological changes of toxigenic Clostridium difficile colitis. The recognition of toxigenic Clostridium difficile infection in IBD children should be strengthened in clinical work.

Discovery of the fourth mobile sulfonamide resistance gene

BackgroundOver the past 75 years, human pathogens have acquired antibiotic resistance genes (ARGs), often from environmental bacteria. Integrons play a major role in the acquisition of antibiotic resistance genes. We therefore hypothesized that focused exploration of integron gene cassettes from microbial communities could be an efficient way to find novel mobile resistance genes. DNA from polluted Indian river sediments were amplified using three sets of primers targeting class 1 integrons and sequenced by long- and short-read technologies to maintain both accuracy and context.ResultsUp to 89% of identified open reading frames encode known resistance genes, or variations thereof (> 1000). We identified putative novel ARGs to aminoglycosides, beta-lactams, trimethoprim, rifampicin, and chloramphenicol, including several novel OXA variants, providing reduced susceptibility to carbapenems. One dihydropteroate synthase gene, with less than 34% amino acid identity to the three known mobile sulfonamide resistance genes (sul1–3), provided complete resistance when expressed in Escherichia coli. The mobilized gene, here named sul4, is the first mobile sulfonamide resistance gene discovered since 2003. Analyses of adjacent DNA suggest that sul4 has been decontextualized from a set of chromosomal genes involved in folate synthesis in its original host, likely within the phylum Chloroflexi. The presence of an insertion sequence common region element could provide mobility to the entire integron. Screening of 6489 metagenomic datasets revealed that sul4 is already widespread in seven countries across Asia and Europe.ConclusionsOur findings show that exploring integrons from environmental communities with a history of antibiotic exposure can provide an efficient way to find novel, mobile resistance genes. The mobilization of a fourth sulfonamide resistance gene is likely to provide expanded opportunities for sulfonamide resistance to spread, with potential impacts on both human and animal health.

Optimizing prophylactic antibiotic regimen in patients admitted fortransrectal ultrasound-guided prostate biopsies: A prospective randomized study.

BackgroundTransrectal ultrasound-guided prostate biopsies (TRUSBx), in spite of being one of the most frequently performed urological office procedures, are associated with a spectrum of complications, most significantly including infection. The aim of the study is to evaluate the prevalence of fluoroquinolone-resistant bacteria in rectal swabs from our local population prior to TRUSBx and to identify risk factors among a patient population harboring fluoroquinolone-resistant organisms.MethodsWe prospectively included 541 men who were submitted for TRUSBx in our center from March 2011 to June 2015. The indications for TRUSBx were an elevated prostate-specific antigen level and/or abnormal digital rectal exam. All patients were randomly divided into two groups: Group 1 (n = 279 cases) who received standard empirical prophylactic antibiotics and Group 2 who received targeted prophylaxis based on a rectal swab culture and susceptibility result. Differences in risk factors between quinolone-resistant and nonresistant patients were compared. Univariate and multivariate analyses were performed to identify independent potential risk factors associated with fluoroquinolone-resistant rectal flora.ResultsSixteen out of 271 men developed infectious complications after TRUSBx in the group receiving standard empirical prophylaxis (5.7%). No men in the group who received targeted prophylactic antibiotic guided by rectal swab developed infectious complications. Among the 262 patients who underwent prebiopsy rectal swab cultures, 76 men (29%) displayed fluoroquinolone-resistant rectal flora (29%). In the multivariate analysis, a history of antibiotic exposure before prostate biopsy was the only independent factor associated with an increased risk of fluoroquinolone resistance.ConclusionDetermining the prevalence of fluoroquinolone resistance in rectal flora has important implications in the selection of targeted prophylactic antibiotic regimens. Antimicrobial profiles guided by rectal swabs may prove useful to optimize prophylaxis prior to TRUSBx; this strategy is effective at reducing the rates of infectious complications, including sepsis, especially in men at higher risk of infectious complications.

Intrahost Evolution of Methicillin-Resistant Staphylococcus aureus USA300 Among Individuals With Reoccurring Skin and Soft-Tissue Infections.

Methicillin-resistant Staphylococcus aureus (MRSA) USA300 is the leading cause of MRSA infections in the United States and has caused an epidemic of skin and soft-tissue infections. Recurrent infections with USA300 MRSA are common, yet intrahost evolution during persistence on an individual has not been studied. This gap hinders the ability to clinically manage recurrent infections and reconstruct transmission networks. To characterize bacterial intrahost evolution, we examined the clinical courses of 4 subjects with 3-6 recurrent USA300 MRSA infections, using patient clinical data, including antibiotic exposure history, and whole-genome sequencing and phylogenetic analysis of all available MRSA isolates (n = 29). Among sequential isolates, we found variability in diversity, accumulation of mutations, and mobile genetic elements. Selection for antimicrobial-resistant populations was observed through both an increase in the number of plasmids conferring multidrug resistance and strain replacement by a resistant population. Two of 4 subjects had strain replacement with a genetically distinct USA300 MRSA population. During a 5-year period in 4 subjects, we identified development of antimicrobial resistance, intrahost evolution, and strain replacement among isolates from patients with recurrent MRSA infections. This calls into question the efficacy of decolonization to prevent recurrent infections and highlights the adaptive potential of USA300 and the need for effective sampling.

Microbiological culture methods for pediatric musculoskeletal infection: a guideline for optimal use.

Culture results affect the diagnosis and treatment of children with musculoskeletal infection. To our knowledge, no previous large-scale study has assessed the relative value of culture methods employed during the evaluation of these conditions. The purpose of this study was to identify an optimal culture strategy for pediatric musculoskeletal infection. Children with musculoskeletal infection were retrospectively studied to assess culture results from the infection site or blood; culture type, including aerobic, anaerobic, fungal, and acid-fast bacteria (AFB); antibiotic exposure history; and clinical history of children with positive culture results. We studied 869 children, including 353 with osteomyelitis, 199 with septic arthritis, forty-two with pyomyositis, and 275 with abscess. The 4537 cultures processed included 1303 aerobic, 903 anaerobic, 340 fungal, 289 AFB, and 1702 blood. Of 3004 specimens sent during initial work-up, positive results occurred in 677 of 1049 aerobic cultures (64.5%), 140 of 763 blood cultures (18.3%), eighteen of 722 anaerobic cultures (2.5%), five of 251 fungal cultures (2.0%), and two of 219 AFB cultures (0.9%). Staphylococcus aureus was the most common pathogen isolated, from 428 (50.7%) of 844 children for whom blood or infection-site culture material was sent (methicillin-resistant S. aureus, 252; and oxacillin-sensitive S. aureus, 176). Cultures were negative in 206 (29.0%) of the 710 children for whom culture material from the site of infection was sent. Children with true-positive anaerobic, fungal, or AFB cultures had a history of immunocompromise, penetrating inoculation, or failed primary treatment. Antibiotic exposure prior to culture-sample acquisition did not interfere with aerobic culture results from the site of infection. Our findings suggest that anaerobic, fungal, and AFB cultures should not be routinely performed during the initial evaluation of children with hematogenous musculoskeletal infection. These cultures should be performed for children with immunocompromise, clinical suspicion of penetrating inoculation, or failed primary treatment.

Updated antibiotic resistance and clinical spectrum of infections caused by Streptococcus pneumoniae in Taiwan: Emphasis on risk factors for penicillin nonsusceptibilities

Streptococcus pneumoniae is one of the leading pathogens causing community-acquired infection with high mortality rates in elderly patients. Emerging antibiotic resistance was found in past decades. Continuous surveillance to monitor changes in antibiotic resistance of S. pneumoniae and associated risk factors are important clinical issues. Isolates of S. pneumoniae collected from six hospitals participating in the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program III (2002) - VI (2008) were enrolled in this study. Bacterial susceptibilities were determined by minimum inhibitory concentration. The clinical data of source patients were collected retrospectively. A total of 330 nonduplicate S. pneumoniae isolates were enrolled in this study. Sputum was the most common specimen source, followed by pus. The mean age of the source patients was 38 years among these 330 patients, and 247 had various infections caused by S.pneumoniae. The overall in-hospital mortality rate was 6% and most (60%)of the mortality occurred in patients older than 65 years. The mortality rates among the patients age 65 years and older and those age 5 years and younger were 12.9% (9 of 70) and 2.4% (2 of 83), respectively. The rates of nonsusceptibility to penicillin by the meningitis criteria (PNSP-M) were 69.0% in 2002, 81.0% in 2004, 73.7% in 2006, and 74.5% in 2008. Resistance to erythromycin and trimethoprim/sulfamethoxazole remained high. Using multivariate analysis, patients with PNSP isolates were more likely to have a history of antibiotic exposure within the previous 15 days compared with patients with penicillin-susceptible (PSSP) isolates (nonmeningitis criteria: 29.70% vs. 18.34%, p=0.0288; meningitis criteria: 25.30% vs. 9.88%, p=0.006). Shock at presentation was the risk factor for in-hospital mortality. Our study demonstrated that the rates of penicillin nonsusceptibility among S.pneumoniae remained high in Taiwan during the study period. Previous antibiotic exposure was the only risk factor for subsequent acquisition of penicillin- nonsusceptible S. pneumoniae compared with penicillin-susceptible S. pneumoniae. Judicious antibiotic use is important to control the spread of drug nonsusceptible S. pneumoniae.