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Bacteremia and endocarditis are two clinical syndromes that, for decades, were managed exclusively with parenteral antimicrobials, irrespective of a given patient's clinical condition, causative pathogen, or its antibiotic susceptibility profile. This clinical approach, however, was based on low-quality data and outdated expert opinions. When a patient's condition has improved, gastrointestinal absorption is not compromised, and an oral antibiotic regimen reaching adequate serum concentrations is available, a switch to oral antibacterials can be applied. Although available evidence has reduced the timing of the oral switch in bacteremia to three days/until clinical improvement, there are only scarce data regarding less than 10-day intravenous antibiotic therapy in endocarditis. Many standard or studied oral antimicrobial dosages are smaller than the approved doses for parenteral administration, which is a risk factor for treatment failure; in addition, the gastrointestinal barrier may affect drug bioavailability, especially when the causative pathogen has a minimum inhibitory concentration that is close to the susceptibility breakpoint. A considerable number of patients infected by such near-breakpoint strains may not be potential candidates for oral step-down therapy to non-highly bioavailable antibiotics like beta-lactams; different breakpoints should be determined for this setting. This review will focus on summarizing findings about pathogen-specific tailoring of oral step-down therapy for bacteremia and endocarditis, but will also present laboratory and clinical data about antibiotics such as beta-lactams, linezolid, and fosfomycin that should be studied more in order to elucidate their role and optimal dosage in this context. [ABSTRACT FROM AUTHOR]

Acute pyelonephritis (APN) is a relatively common community-acquired infection, particularly in women. The early appropriate antibiotic treatment of this potentially life-threatening infection is associated with improved outcomes. The international management guidelines for complicated urinary tract infections and APN recommend using oral antibiotics with <10% resistance among urinary pathogens. However, increasing antibiotic resistance rates among Escherichia coli and other Enterobacterales to fluoroquinolones, trimethoprim-sulfamethoxazole (TMP-SMX), and beta-lactams has left patients without reliable oral antibiotic treatment options for APN. This narrative review proposes using precision medicine concepts to improve empirical antibiotic therapy for APN in ambulatory settings. Whereas resistance rates to a particular antibiotic class may exceed 10% at the population-based level, the predicted antibiotic resistance rates based on patient-specific risk factors fall under 10% in many patients with APN on the individual level. The utilization of clinical tools for the prediction of fluoroquinolones, TMP-SMX, and third-generation cephalosporin resistance improves the ambulatory antibiotic management of APN. It may also reduce the need to switch antibiotic therapy later based on the in vitro antibiotic susceptibility testing results of bacterial isolates in urinary cultures. This approach may mitigate the burden of increasing antibiotic resistance in the community by ensuring that the initial antibiotic prescribed has the highest likelihood of treating APN appropriately. [ABSTRACT FROM AUTHOR]

Introduction: Not enough data exist to inform the optimal duration and type of antimicrobial therapy against GN infections in critically ill patients. Methods: Narrative review based on a literature search through PubMed and Cochrane using the following keywords: "multi-drug resistant (MDR)", "extensively drug resistant (XDR)", "pan-drug-resistant (PDR)", "difficult-to-treat (DTR) Gram-negative infection," "antibiotic duration therapy", "antibiotic combination therapy" "antibiotic monotherapy" "Gram-negative bacteremia", "Gram-negative pneumonia", and "Gram-negative intra-abdominal infection". Results: Current literature data suggest adopting longer (≥10–14 days) courses of synergistic combination therapy due to the high global prevalence of ESBL-producing (45–50%), MDR (35%), XDR (15–20%), PDR (5.9–6.2%), and carbapenemases (CP)/metallo-β-lactamases (MBL)-producing (12.5–20%) Gram-negative (GN) microorganisms (i.e., Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii). On the other hand, shorter courses (≤5–7 days) of monotherapy should be limited to treating infections caused by GN with higher (≥3 antibiotic classes) antibiotic susceptibility. A general approach should be based on (i) third or further generation cephalosporins ± quinolones/aminoglycosides in the case of MDR-GN; (ii) carbapenems ± fosfomycin/aminoglycosides for extended-spectrum β-lactamases (ESBLs); and (iii) the association of old drugs with new expanded-spectrum β-lactamase inhibitors for XDR, PDR, and CP microorganisms. Therapeutic drug monitoring (TDM) in combination with minimum inhibitory concentration (MIC), bactericidal vs. bacteriostatic antibiotics, and the presence of resistance risk predictors (linked to patient, antibiotic, and microorganism) should represent variables affecting the antimicrobial strategies for treating GN infections. Conclusions: Despite the strategies of therapy described in the results, clinicians must remember that all treatment decisions are dynamic, requiring frequent reassessments depending on both the clinical and microbiological responses of the patient. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is one of the biggest threats to human health worldwide. The World Health Organization (WHO, Geneva, Switzerland) has launched the "One-Health" approach, which encourages assessment of antibiotic-resistant genes (ARGs) within environments shared by human-animals-plants-microbes to constrain and alleviate the development of AMR. Aerosols as a medium to disseminate ARGs, have received minimal attention. In the present study, we investigated the distribution and abundance of ARGs in indoor and outdoor aerosols collected from an urban location in Kuwait and the interior of three hospitals. The high throughput quantitative polymerase chain reaction (HT-qPCR) approach was used for this purpose. The results demonstrate the presence of aminoglycoside, beta-lactam, fluoroquinolone, tetracycline, macrolide-lincosamide-streptogramin B (MLSB), multidrug-resistant (MDR) and vancomycin-resistant genes in the aerosols. The most dominant drug class was beta-lactam and the genes were IMP-2-group (0.85), Per-2 group (0.65), OXA-54 (0.57), QnrS (0.50) and OXA-55 (0.55) in the urban non-clinical settings. The indoor aerosols possessed a richer diversity (Observed, Chao1, Shannon's and Pielou's evenness) of ARGs compared to the outdoors. Seasonal variations (autumn vs. winter) in relative abundances and types of ARGs were also recorded (R2 of 0.132 at p < 0.08). The presence of ARGs was found in both the inhalable (2.1 µm, 1.1 µm, 0.7 µm and < 0.3 µm) and respirable (>9.0 µm, 5.8 µm, 4.7 µm and 3.3 µm) size fractions within hospital aerosols. All the ARGs are of pathogenic bacterial origin and are hosted by pathogenic forms. The findings present baseline data and underpin the need for detailed investigations looking at aerosol as a vehicle for ARG dissemination among human and non-human terrestrial biota. [ABSTRACT FROM AUTHOR]

(1) Background: Risk factors for extended-spectrum beta-lactamase (ESBL) infections could vary geographically. The purpose of this study was to identify local risk factors for ESBL production in patients with Gram-negative bacteremia. (2) Methods: This retrospective observational study included adult patients admitted from January 2019 to July 2021 and had positive blood cultures for E. coli, K. pneumoniae, K. oxytoca, and P. mirabilis. Patients with ESBL infection were matched to a non-ESBL-producing infection with the same organism. (3) Results: A total of 150 patients were included: 50 in the ESBL group and 100 in the non-ESBL group. Patients in the ESBL group had a longer length of stay (11 vs. 7 days, p < 0.001), but not increased mortality (14% vs. 15%, p = 0.87) Multivariate analysis identified the receipt of >1 antibiotic in the last 90 days as a risk factor for ESBL infection (OR = 3.448, 95% CI = 1.494–7.957; p = 0.004); (4) Conclusions: Recent antimicrobial use was identified as an independent risk factors for ESBL-producing Enterobacterales infections. Knowledge of this risk may improve empirical therapy and reduce inappropriate use. [ABSTRACT FROM AUTHOR]

Introduction: There is marked heterogeneity in clinicians' choice of antibiotic duration for pediatric urinary tract infections (UTIs). Most patients with bacterial UTIs still receive between 7 and 10 days of antibiotics. Prolonged antibiotic exposure drives the emergence of resistance and increases the occurrence of adverse effects. There is increasing evidence that shorter antibiotic regimens may be equally effective compared with longer ones. However, studies evaluating shorter therapies in children hospitalized with urinary tract infections have not yet been performed. Methods: We performed a retrospective study comparing children hospitalized with UTIs treated with a short antibiotic (<7 days) or standard antibiotic treatment. The primary aim of our study was to assess the efficacy of a shorter antibiotic therapy for children with UTIs, compared with an historical group of children treated with a standard 7–14 days course. Results: 112 patients, 46 of which were females (41.1%) with a median age 6 months were enrolled. A total of 33 patients (29.5%) underwent a short therapy. All patients were successfully discharged from the acute episode, independently from antibiotic duration. Short therapy was associated with a lower risk of urinary tract relapse (22 relapses (95.6%) in the standard group, 1 (4.4%) in the short group; OR 0.081; 95%CI 0.01–0.63). Conclusions: Short antibiotic therapy was equivalent to standard duration therapy for the cure of UTIs in hospitalized children and was also associated with a lower rate of recurrences. This study provides the basis for a larger prospective randomized study to address the role of short antibiotic therapies in children with UTIs requiring hospitalization [ABSTRACT FROM AUTHOR]

Background: Antibiotic Resistance is an imminent global public health threat. Antibiotic resistance emerged in healthcare settings and has now moved on to the community settings. This study was conducted to identify the rates of asymptomatic colonization with selected antibiotic resistant organisms, (Methicillin Resistant Staphylococcus aureus (MRSA), Extended Spectrum Beta Lactamase (ESBL) producing Escherichia coli and Klebsiella spp and carbapenem resistant E.coli and Klebsiella spp) - among a group of university students in Sri Lanka. Identification of genetic determinants of MRSA and ESBL was an additional objective of the study.Methods: A self - collected nasal swab and a peri-rectal swab collected after passing stools were obtained. Routine microbiological methods were used for the isolation S.aureus from the nasal swab and E.coli and Klebsiella species from the peri-rectal swab. Antibiotic sensitivity testing was performed as recommended by clinical and laboratory standard institute (CLSI). Three (3) genes that are responsible for ESBL production; blaCTX-M, blaSHV, and blaTEM were tested using previously described primers and PCR procedures. Identification of MecA and PVL genes attributed to MRSA was also done with PCR.Results: A total of 322 participants between 21 and 28 years were recruited representing 5 different faculties of study. Seventy one (22.0%) were colonized with S.aureus and 14 among them with MRSA, making the MRSA colonization rate of 4.3%. Forty five (15%) of the participants were colonized with an ESBL producing E.coli or Klebsiella spp. No one was colonized with carbapenem resistant E.coli or Klebsiella species. Of the 45 ESBL producers the commonest genetic determinant identified was blaCTX-M (n = 36), while 16 isolates had blaTEM and 7 had blaSHV. Similarly, of the 14 isolates identified as MRSA, 3 (21.4%) were found to be PVL positive while 11 (78.6%) were MecA positive.Conclusions: A high rate of colonization with ESBL producing E.coli and Klebsiella species was noted in our study group. [ABSTRACT FROM AUTHOR]

A 30-year-old female with a medical history of gastrointestinal reflux and intravenous methamphetamine use was admitted to the hospital with complaints of fever and chills. Pantoae agglomerans was isolated in one out of two blood cultures. Although information was limited about the duration and efficacy of oral antibiotics to treat this type of infection, the patient recovered with oral antibiotic treatment following a short course of intravenous antibiotics. [ABSTRACT FROM AUTHOR]

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Background Quinolone resistance has been documented in the pediatric population, although their use is limited in children. This study investigated the effect of maternal quinolone use on gram-negative bacterial resistance to quinolones in their offspring. Methods We conducted a population-based, unmatched case-control study during 2010–2017. Cases were all children aged 0.5–17 years with community acquired, gram-negative quinolone-resistant bacteriuria. Controls were similar children with quinolone-sensitive bacteriuria. Only the first positive urine cultures for each child were included. Data on quinolones dispensed to the mother, any antibiotics dispensed to the children, age, sex, ethnicity, and prior hospitalizations were collected. Children with previous quinolone use were excluded. Results The study population consisted of 40 204 children. Quinolone resistance was detected in 2182 (5.3%) urine cultures. The median age was 5 years, with 93.7% females and 77.6% Jewish. A total of 26 937 (65%) of the children received any antibiotic and 1359 (3.2%) of the mothers received quinolones in the 6 months preceding bacteriuria. Independent risk factors were quinolone dispensed to the mothers (odds ratio [OR], 1.50 [95% confidence interval {CI}, 1.22–1.85]), Arab ethnicity (OR, 1.99 [95% CI, 1.81–2.19]), and antibiotic dispensed to the child (OR, 1.54 [95% CI, 1.38–1.71]). Compared with children aged 12–17 years, younger children had 1.33–1.43 increased odds for quinolone-resistant bacteriuria. Conclusions Quinolone prescription to mothers was linked to increased risk of community-acquired, quinolone-resistant bacteria in their offspring, by about 50%. This is another example of the deleterious ecological effects of antibiotic use and should be considered when prescribing antibiotics. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether prior exposure to non-fluoroquinolone antibiotics increases the risk of fluoroquinolone resistance in Escherichia coli.Methods: This was a secondary analysis of data collected retrospectively in a case-control study linking microbiological test results (isolated bacteria and their susceptibility) of urine samples routinely collected from primary, secondary and tertiary care patients in Belgium with information on prior antibiotic use at the patient level up to 1 year previously.Results: In urine samples from 6125 patients, 7204 E. coli isolates were retrieved [1949 fluoroquinolone-resistant isolates (cases) and 5255 fluoroquinolone-susceptible isolates (controls)]. After adjusting for potential confounders (including fluoroquinolone use) and correcting for multiple testing there were lower odds of fluoroquinolone resistance in E. coli isolates after exposure to cefazolin (OR = 0.65; 95% CI = 0.52-0.81; P = 0.00014) and higher odds after exposure to trimethoprim/sulfamethoxazole (OR = 1.56; 95% CI = 1.23-1.97; P =0.00020) or nitrofurantoin (OR = 1.50; 95% CI = 1.23-1.84; P =0.000083). A sensitivity analysis excluding samples with antibiotic use during the 6 months prior to the sampling date confirmed the higher odds of fluoroquinolone resistance after exposure to trimethoprim/sulfamethoxazole and nitrofurantoin.Conclusions: Assuming no residual confounding or other biases, this study suggests that exposure to non-fluoroquinolone antibiotics, i.e. trimethoprim/sulfamethoxazole and nitrofurantoin, might be causally related to fluoroquinolone resistance in E. coli isolates from urinary samples. Future prospective research is needed to confirm non-fluoroquinolone antibiotics as potential drivers of fluoroquinolone resistance. [ABSTRACT FROM AUTHOR]

Since sepsis was first defined, sepsis management has remained challenging. To improve mortality rates for sepsis and septic shock, an accurate diagnosis and prompt administration of appropriate antibiotics are essential. The goals of antimicrobial stewardship are to achieve optimal clinical outcomes and to ensure cost-effectiveness and minimal unintended consequences, such as toxic effects and development of resistant pathogens. A combination of inadequate diagnostic criteria for sepsis and time pressure to provide broad-spectrum antimicrobial therapy remains an obstacle for antimicrobial stewardship. Efforts such as selection of appropriate empirical antibiotics and de-escalation or determination of whether or not to stop antibiotics may help to improve a patient's clinical prognosis as well as the successful implementation of antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

Background Carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonizes the gastrointestinal tract of intensive care unit (ICU) patients, and CRPA colonization puts patients at increased risk of CRPA infection. Prior studies have not examined relationships between the microbiota, medications, and CRPA colonization acquisition. Methods Data and perirectal swabs were obtained from a cohort of ICU patients at the University of Maryland Medical Center. Patients (N = 109) were classified into 3 groups by CRPA colonization-acquisition status and antimicrobial exposure. We conducted 16S ribosomal RNA gene sequencing of an ICU admission swab and ≥1 additional swab and evaluated associations between patient characteristics, medications, the gastrointestinal microbiota, and CRPA colonization acquisition. Results ICU patients had low levels of diversity and high relative abundances of pathobionts. Piperacillin-tazobactam was prescribed more frequently to patients with CRPA colonization acquisition than those without. Piperacillin-tazobactam was associated with low abundance of potentially protective taxa (eg, Lactobacillus and Clostridiales) and increased risk of Enterococcus domination (odds ratio [OR], 5.50; 95% confidence interval [CI], 2.03–14.92). Opioids were associated with dysbiosis in patients who did not receive antibiotics; potentially protective Blautia and Lactobacillus were higher in patients who did not receive opioids. Several correlated taxa, identified at ICU admission, were associated with lower risk of CRPA colonization acquisition (OR, 0.58; 95% CI,.38–.87). Conclusions Antibiotics differed in their impact on the microbiota, with piperacillin-tazobactam being particularly damaging. Certain bacterial taxa (eg, Clostridiales) were negatively associated with CRPA colonization acquisition. These taxa may be markers of risk for CRPA colonization acquisition and/or serve a protective role. [ABSTRACT FROM AUTHOR]

Up to now, little has been known about the prevalence and clinical relevance of colonisation of asymptomatic pregnant women with methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA) or extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. In this two-centre cross-sectional study, we evaluated the performance and importance of screening at different times and different locations for colonisation in pregnant women and newborns. Between October 2013 and December 2015, four samples were collected from pregnant women, two from newborns at birth and three from 3-day-old newborns. Samples were screened on culturing media and were confirmed with molecular methods. MSSA was used as a surrogate for MRSA, as the two share most microbiologic characteristics and colonisation patterns. Of 763 pregnant women, 14.5% (111) were colonised with MSSA, 0.4% (3) with MRSA and 2.6% (20) with ESBL-producing E. coli. Of 658 newborns, 0.9% (10) were colonised with MSSA at birth and 13.1% (70) at 3 days old, 0.5% (3) were colonised with MRSA and 2.6% (17) with ESBL-producing E. coli. Nasal sampling identified 91.0% of MSSA-colonised pregnant women and 60.0% of newborns. In newborns, nasal and umbilical sampling at 3 days after birth discovered 84.0% of colonised cases. For ESBL-producing E. coli, the perianal region was positive in all colonised pregnant women and in 88.2% of colonised newborns. Combining nasal and perianal swabs is optimal when screening for antibiotic-resistant bacteria in pregnant women. Nasal, perianal and umbilical sample collection from 3-day-old newborns significantly increased the sensitivity compared to screening immediately after birth. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) caused by antibiotic-resistant Gram-negative bacteria are a growing concern due to limited therapeutic options. Gram-negative bacteria, specifically Enterobacteriaceae, are common causes of both community-acquired and hospital acquired UTIs. These organisms can acquire genes that encode for multiple antibiotic resistance mechanisms, including extended-spectrum-lactamases (ESBLs), AmpC- β -lactamase, and carbapenemases. The assessment of suspected UTI includes identification of characteristic symptoms or signs, urinalysis, dipstick or microscopic tests, and urine culture if indicated. UTIs are categorized according to location (upper versus lower urinary tract) and severity (uncomplicated versus complicated). Increasing rates of antibiotic resistance necessitate judicious use of antibiotics through the application of antimicrobial stewardship principles. Knowledge of the common causative pathogens of UTIs including local susceptibility patterns are essential in determining appropriate empiric therapy. The recommended first-line empiric therapies for acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females is a 5-day course of nitrofurantion or a 3-g single dose of fosfomycin tromethamine. Second-line options include fluoroquinolones and β-lactams, such as amoxicillin-clavulanate. Current treatment options for UTIs due to AmpC- β -lactamase-producing organisms include fosfomycin, nitrofurantion, fluoroquinolones, cefepime, piperacillin-tazobactam and carbapenems. In addition, treatment options for UTIs due to ESBLs-producing Enterobacteriaceae include nitrofurantion, fosfomycin, fluoroquinolones, cefoxitin, piperacillin-tazobactam, carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, and aminoglycosides. Based on identification and susceptibility results, alternatives to carbapenems may be used to treat mild-moderate UTIs caused by ESBL-producing Enterobacteriaceae. Ceftazidime-avibactam, colistin, polymixin B, fosfomycin, aztreonam, aminoglycosides, and tigecycline are treatment options for UTIs caused by carbapenem-resistant Enterobacteriaceae (CRE). Treatment options for UTIs caused by multidrug resistant (MDR)-Pseudomonas spp. include fluoroquinolones, ceftazidime, cefepime, piperacillin-tazobactam, carbapenems, aminoglycosides, colistin, ceftazidime-avibactam, and ceftolozane-tazobactam. The use of fluoroquinolones for empiric treatment of UTIs should be restricted due to increased rates of resistance. Aminoglycosides, colistin, and tigecycline are considered alternatives in the setting of MDR Gram-negative infections in patients with limited therapeutic options. [ABSTRACT FROM AUTHOR]

Background: The emergence and spread of Carbapenem-resistant Escherichia coli (CREC) is becoming a serious problem in Chinese hospitals, however, the data on this is scarce. Therefore, we investigate the risk factors for healthcare-associated CREC infection and study the incidence, antibiotic resistance and medical costs of CREC infections in our hospital.Methods: We conducted a retrospective, matched case-control-control, parallel study in a tertiary teaching hospital. Patients admitted between January 2012 and December 2015 were included in this study. For patients with healthcare-associated CREC infection, two matched subject groups were created; one group with healthcare-associated CSEC infection and the other group without infection.Results: Multivariate conditional logistic regression analysis demonstrated that prior hospital stay (<6 months) (OR:3.96; 95%CI:1.26-12.42), tracheostomy (OR:2.24; 95%CI: 1.14-4.38), central venous catheter insertion (OR: 8.15; 95%CI: 2.31-28.72), carbapenem exposure (OR: 12.02; 95%CI: 1.52-95.4), urinary system disease (OR: 16.69; 95%CI: 3.01-89.76), low hemoglobin (OR: 2.83; 95%CI: 1.46-5.50), and high blood glucose are associated (OR: 7.01; 95%CI: 1.89-26.02) with CREC infection. Total costs (p = 0.00), medical examination costs (p = 0.00), medical test costs (p = 0.00), total drug costs (p = 0.00) and ant-infective drug costs (p = 0.00) for the CREC group were significantly higher than those for the no infection group. Medical examination costs (p = 0.03), total drug costs (p = 0.03), and anti-infective drug costs (p = 0.01) for the CREC group were significantly higher than for the CSEC group. Mortality in CREC group was significantly higher than the CSEC group (p = 0.01) and no infection group (p = 0.01).Conclusion: Many factors were discovered for acquisition of healthcare-associated CREC infection. CREC isolates were resistant to most antibiotics, and had some association with high financial burden and increased mortality. [ABSTRACT FROM AUTHOR]

Background Drug resistant organisms pose an increasing threat to the successful treatment of common infections. Understanding colonization patterns of these bacteria is important for effective antibiotic treatment and infection control guidelines. Methods A prospective observational study was performed to determine the prevalence of colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E), methicillinresistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE) among patients admitted via the emergency department to a public tertiary hospital in Singapore. Anterior nares, groin, axillary and rectal swabs were collected at admission and cultured using standard bacteriological techniques. Clinical data including healthcare contact within the past 12 months and recent antibiotic use was collected and analyzed using a logistic regression model. Results 1006 patients were screened. 124 (12.4%) were colonized by ESBL-E, 18 (1.8%) by MRSA while no VRE was detected. Antibiotic use within the past month was the only significant predictor for ESBL-E colonization in the regression model, with an adjusted odds ratio (AOR) of 2.58 (1.04 to 6.42). In participants recently prescribed antibiotics and hospitalized in the previous 3 months, 29.4% were colonized by ESBL-E. This represented 20.2% of the total ESBL-E burden, and ESBL-E was also detected in 6.3% of participants with no healthcare contact. Hospitalization and outpatient hospital visits predicted MRSA colonization in the univariate analysis. Neither was statistically significant in the logistic regression model, with AORs for MRSA colonization following hospitalization in the past 3 and 12 months of 3.81 [95% CI 0.84-17.28] and 3.48 [0.64-18.92] respectively. Conclusion A high prevalence of colonization with ESBL-E was evident among patients at admission, even in the absence of recent antibiotic use or contact with healthcare. [ABSTRACT FROM AUTHOR]

Antibiotic resistance mechanisms reported in Gram-negative bacteria are causing a worldwide health problem. The continuous dissemination of 'multidrug-resistant' (MDR) bacteria drastically reduces the efficacy of our antibiotic 'arsenal' and consequently increases the frequency of therapeutic failure. In MDR bacteria, the overexpression of efflux pumps that expel structurally unrelated drugs contributes to the reduced susceptibility by decreasing the intracellular concentration of antibiotics. During the last decade, several clinical data have indicated an increasing involvement of efflux pumps in the emergence and dissemination of resistant Gram-negative bacteria. It is necessary to clearly define the molecular, functional and genetic bases of the efflux pump in order to understand the translocation of antibiotic molecules through the efflux transporter. The recent investigation on the efflux pump AcrB at its structural and physiological levels, including the identification of drug affinity sites and kinetic parameters for various antibiotics, may pave the way towards the rational development of an improved new generation of antibacterial agents as well as efflux inhibitors in order to efficiently combat efflux-based resistance mechanisms. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infections (UTIs) are the most commonly treated infection among nursing home residents. Even in the absence of specific (e.g., dysuria) or non-specific (e.g., fever) signs or symptoms, residents frequently receive an antibiotic for a suspected infection. This research investigates factors associated with the use of antibiotics to treat asymptomatic bacteriuria (ASB) among nursing home residents. Methods: This was a cross-sectional study involving multi-level multivariate analyses of antibiotic prescription data for residents in four nursing homes in central Texas. Participants included all nursing home residents in these homes who, over a six-month period, received an antibiotic for a suspected UTI. We investigated what factors affected the likelihood that a resident receiving an antibiotic for a suspected UTI was asymptomatic. Results: The most powerful predictor of antibiotic treatment for ASB was the presence of an indwelling urinary catheter. Over 80 percent of antibiotic prescriptions written for catheterized individuals were written for individuals with ASB. For those without a catheter, record reviews identified 204 antibiotic prescriptions among 151 residents treated for a suspected UTI. Almost 50% of these prescriptions were for residents with no documented UTI symptoms. Almost three-quarters of these antibiotics were ordered after laboratory results were available to clinicians. Multivariate analyses indicated that resident characteristics did not affect the likelihood that an antibiotic was prescribed for ASB. The only statistically significant factor was the identity of the nursing home in which a resident resided. Conclusions: We confirm the findings of earlier research indicating frequent use of antibiotics for ASB in nursing homes, especially for residents with urinary catheters. In this sample of nursing home residents, half of the antibiotic prescriptions for a suspected UTI in residents without catheters occurred with no documented signs or symptoms of a UTI. Urine studies were performed in almost all suspected UTI cases in which an antibiotic was prescribed. Efforts to improve antibiotic stewardship in nursing homes must address clinical decision-making solely on the basis of diagnostic testing in the absence of signs or symptoms of a UTI. [ABSTRACT FROM AUTHOR]

Background. The prevalence of fecal colonization with Escherichia coli that has reduced susceptibility to fluoroquinolones is unknown. A detailed characterization of such isolates is limited. Methods. We conducted 3 annual fecal surveillance initiatives at 2 hospitals from 2002 to 2004. All E. coli isolates with reduced susceptibility to fluoroquinolones (minimum inhibitory concentration [MIC] to levofloxacin, ≥0.125 µg/mL) were identified. We characterized gyrA and parC mutations and organic solvent tolerance (OST). Isolates were compared using pulsed-field gel electrophoresis. Results. Of 789 fecal samples, 149 (18.9%) revealed E. coli with reduced susceptibility to fluoroquinolones. Of 149 isolates, 102 (68.5%) had a MIC ≥8 µg/mL, 138 (92.6%) had ≥1 gyrA mutation, 101 (67.8%) had ≥1 parC mutation, and 59 (39.6%) demonstrated OST. Isolates with a MIC <8 versus !8 mg/mL had more target mutations (median, 3 vs. 1; P < .001) and more often exhibited OST (51% vs. 15%; P < 0.001). Of 149 isolates, 144 (96.6%) demonstrated a MIC ≥16 µg/mL to nalidixic acid. The prevalence of OST differed across study years (P = .01). There was no clonal spread of isolates. Conclusions. Colonization by E. coli with reduced fluoroquinolone susceptibility is common, and fluoroquinolone-resistance characteristics differ significantly over time. Resistance to nalidixic acid may be useful in the identification of E. coli with early resistance mutations. [ABSTRACT FROM AUTHOR]

We conducted a cross-sectional study to determine the prevalence of, and risk factors for, colonization with fluoroquinolone (FQ)-resistant Escherichia coli in residents in a long-term care facility. FQ-resistant E. coli were identified from rectal swabs for 25 (51%) of 49 participants at study entry. On multivariable analyses, prior FQ use was the only independent risk factor for FQ-resistant E. coli carriage and was consistent for FQ exposures in the previous 3, 6, 9, or 12 months. Pulsed-field gel electrophoresis of FQ-resistant E. coli identified clonal spread of 1 strain among 16 residents. Loss (6 residents) or acquisition (7 residents) of FQ-resistant E. coli was documented and was associated with de novo colonization with genetically distinct strains. Unlike the case in the hospital setting, FQ-resistant E. coli carriage in long-term care facilities is associated with clonal spread. [ABSTRACT FROM AUTHOR]

The feasibility of gastrointestinal (GI) microbiome work in a pediatric intensive care unit (PICU) to determine the GI microbiota composition of infants as compared to control infants from the same hospital was investigated. In a single-site observational study at an urban quaternary care children's hospital in Western Michigan, subjects less than 6 months of age, admitted to the PICU with severe respiratory syncytial virus (RSV) bronchiolitis, were compared to similarly aged control subjects undergoing procedural sedation in the outpatient department. GI microbiome samples were collected at admission (n = 20) and 72 h (n = 19) or at time of sedation (n = 10). GI bacteria were analyzed by sequencing the V4 region of the 16S rRNA gene. Alpha and beta diversity were calculated. Mechanical ventilation was required for the majority (n = 14) of study patients, and antibiotics were given at baseline (n = 8) and 72 h (n = 9). Control subjects' bacterial communities contained more Porphyromonas, and Prevotella (p = 0.004) than those of PICU infants. The ratio of Prevotella to Bacteroides was greater in the control than the RSV infants (mean ± SD—1.27 ± 0.85 vs. 0.61 ± 0.75: p = 0.03). Bacterial communities of PICU infants were less diverse than those of controls with a loss of potentially protective populations. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the clinical and organizational impact of an active re-evaluation (on day 10) of patients on antibiotic treatment diagnosed with bloodstream infections (BSIs). A prospective, single center, pre-post quasi-experimental study was performed. Patients were enrolled at the time of microbial BSI confirmation. In the pre-intervention phase (August 2014–August 2015), clinical status and antibiotic regimen were re-evaluated at day 3. In the intervention phase (January 2016–January 2017), clinical status and antibiotic regimen were re-evaluated at day 3 and day 10. Primary outcomes were rate of optimal therapy, duration of antibiotic therapy, length of hospitalization, and 30-day mortality. A total of 632 patients were enrolled (pre-intervention period, n = 303; intervention period, n = 329). Average duration of therapy reduced from 18.1 days (standard deviation (SD), 11.4) in the pre-intervention period to 16.8 days (SD, 12.7) in the intervention period (p < 0.001). Similarly, average length of hospitalization decreased from 24.1 days (SD, 20.8) to 20.6 days (SD, 17.7) (p = 0.001). No inter-group difference was found for the rate of 30-day mortality. In patients with BSI, re-evaluation of clinical status and antibiotic regimen at day 3 and 10 after microbiological diagnosis was correlated with a reduction in the duration of antibiotic therapy and hospital stay. The intervention is simple and has a low impact on overall costs. [ABSTRACT FROM AUTHOR]

Background: Increased resistance to third-generation cephalosporin (3GC) is a serious concern for community-onset Escherichia coli infection because this resistance easily delays effective treatment. This study surveyed the current antimicrobial resistance pattern among E. coli isolates that cause community-onset bacteremia, with a special focus on the prevalence of and the risk factors for 3GC resistance, and determined factors for poor outcomes among patients with community-onset E. coli bacteremia.Methods: This retrospective study was conducted at a tertiary-care teaching hospital in Taiwan. All adult patients with community-onset E. coli bacteremia between January 1, 2015, and December 31, 2015 were enrolled and were divided into two groups depending on whether the E. coli isolate was susceptible to 3GCs. Risk factors for 3GC resistance, 14-day all-cause mortality, and length of hospital stay were analyzed.Results: The overall rate of 3GC resistance among E. coli isolates causing community-onset bacteremia was 19.7%, whereas it was 9.6% if only isolates causing community-acquired bacteremia were considered. Independent risk factors for 3GC-resistant community-onset E. coli bacteremia were hospitalization within the past 1 year (odds ratio: 2.4, 95% confidence interval: 1.6-3.7, P < 0.001), exposure to antibiotics within the past 15 days (2.6, 1.4-4.9, P = 0.002), residence in nursing home or long-term care facility (3.6, 1.0-12.3, P = 0.044), presence of underlying genitourinary disease (1.9, 1.2-2.9, P = 0.005), and presence of indwelling implantable intravenous port (2.2, 1.1-4.1, P = 0.021). 3GC resistance was independently associated with increased length of hospital stays (P < 0.001).Conclusion: In this study, the prevalence of 3GC resistance was high among both patients with community-onset and those with community-acquired E. coli bacteremia. 3GC resistance is a strong independent risk factor for length of hospital stay. The effectiveness of empirical antibiotic treatment would partially explain the impact of 3GC resistance, but more evidence is needed. The choice of appropriate empirical antibiotics for community-onset E. coli bacteremia might impact outcomes in terms of the length of hospital stay and need to be individualized according to the patient-specific risk for acquiring drug-resistant pathogens. [ABSTRACT FROM AUTHOR]

Background: Healthcare exposure may increase drug-resistant Enterobacteriaceae colonization risk. Nascent antimicrobial stewardship efforts in low- and middle-income countries require setting-specific data. We aimed to evaluate risk factors for inpatient drug resistant Enterobacteriaceae colonization in a resource-limited setting in India.Methods: Patients age ≥ 6 months admitted with ≥24 h of fever to a tertiary hospital in Pune, India were enrolled in a prospective cohort. Perirectal swabs, collected on admission and hospitalization day 3 or 4, were cultured in vancomycin- and ceftriaxone-impregnated media to assess for ceftriaxone-resistant Enterobacteriaceae (CTRE) and carbapenem-resistant Enterobacteriaceae (CPRE). Multivariable analyses assessed risk factors for drug-resistant Enterobacteriaceae colonization among participants without admission colonization.Results: Admission perirectal swabs were collected on 897 participants; 87 (10%) had CTRE and 14 (1.6%) had CPRE colonization. Admission CTRE colonization was associated with recent healthcare contact (p < 0.01). Follow-up samples were collected from 620 participants, 67 (11%) had CTRE and 21 (3.4%) had CPRE colonization. Among 561 participants without enrollment CTRE colonization, 49 (9%) participants were colonized with CTRE at follow-up. Detection of CTRE colonization among participants not colonized with CTRE at admission was independently associated with empiric third generation cephalosporin treatment (adjusted odds ratio [OR] 2.9, 95% CI 1.5-5.8). Follow-up transition to CPRE colonization detection was associated with ICU admission (OR 3.0, 95% CI 1.0-8.5).Conclusions: Patients who receive empiric third generation cephalosporins and are admitted to the ICU rapidly develop detectable CTRE and CPRE colonization. Improved antimicrobial stewardship and infection control measures are urgently needed upon hospital admission. [ABSTRACT FROM AUTHOR]