The purpose of the study was to evaluate how use of antibiotics precedes the presence of ESBL-producing E.coli in general practice. The authors performed a triple-case-control study where three case groups were individually compared to a single control group of uninfected individuals. Urine samples were prospectively collected and retrospective statistical analyses were done. This study included 98 cases with urinary tract infection (UTI) caused by ESBL-producing E. coli, 174 with antibiotic-resistant (non-ESBL) E. coli, 177 with susceptible E. coli and 200 with culture negative urine samples. Case groups had significantly higher use of antibiotics than the control group within 30 days before infection (p < 0.0001). The ESBL group had significantly more hospital admissions than the other case groups (p < 0.05). Hospital admission was an independent risk factor for community onset UTI by ESBL-producing E. coli. Exposure to antibiotics was a risk factor for UTI with E. coli, while prior antibiotic usage was not an indisputable predictor for infection with ESBL-producing E.coli in general practice.

BackgroundEscherichia coli is the most common cause of urinary tract infection (UTI). The pathogenic isolates are becoming increasingly resistant to antibiotics; with a worldwide dissemination of resistant sequence types (ST). We characterized three different uropathogenic E. coli populations, from non-hospitalized patients to describe the genetic kinship between resistant and susceptible isolates. We studied the populations by use of multi-locus sequence typing (MLST) and abbreviated-multi locus variable number of tandem repeat analysis (a-MLVA). Urine samples submitted for testing, by general practitioners, were identified at Dept. of Clinical Microbiology at Hvidovre Hospital, Denmark, from Oct. 2011 to July 2012. We included 94 fully susceptible, 94 resistant (non-ESBL) and 98 Extended Spectrum Beta-lactamases- (ESBL)-producing E. coli isolates.ResultsThe ESBL population was dominated vastly by ST131 (51 %), ST38 (9 %) and ST69 (6 %). In the resistant group ST69 (18 %), ST73 (11 %) and ST131 (15 %) were the largest clusters. In the susceptible population more STs and a-MLVA codes were identified compared to the other groups and ST73 and ST95 were found as the only clusters with 16 % and 6 %, respectively. Ninety-eight per cent of the ESBL-producing E. coli isolates were CTX-M-producers.ConclusionST131 dominated the population of community-associated uropathogenic ESBL-producing E. coli, but was less frequent among non-ESBL-producing E. coli. The fully susceptible E. coli population was a much more diverse group than the resistant and ESBL-producing E. coli populations. Overall, these findings suggest that dominant ESBL-producing lineages are derived from UPEC lineages already established in the general UPEC population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0681-z) contains supplementary material, which is available to authorized users.

BackgroundA basic paradigm of human infection is that acute bacterial disease is caused by fast growing planktonic bacteria while chronic infections are caused by slow-growing, aggregated bacteria, a phenomenon known as a biofilm. For lung infections, this paradigm has been thought to be supported by observations of how bacteria proliferate in well-established growth media in the laboratory—the gold standard of microbiology.ObjectiveTo investigate the bacterial architecture in sputum from patients with acute and chronic lung infections.MethodsAdvanced imaging technology was used for quantification and direct comparison of infection types on fresh sputum samples, thereby directly testing the acute versus chronic paradigm.ResultsIn this study, we compared the bacterial lifestyle (planktonic or biofilm), growth rate and inflammatory response of bacteria in freshly collected sputum (n=43) from patient groups presenting with acute or chronic lung infections. We found that both acute and chronic lung infections are dominated by biofilms (aggregates of bacteria within an extracellular matrix), although planktonic cells were observed in both sample types. Bacteria grew faster in sputum from acute infections, but these fast-growing bacteria were enriched in biofilms similar to the architecture thought to be reserved for chronic infections. Cellular inflammation in the lungs was also similar across patient groups, but systemic inflammatory markers were only elevated in acute infections.ConclusionsOur findings indicate that the current paradigm of equating planktonic with acute and biofilm with chronic infection needs to be revisited as the difference lies primarily in metabolic rates, not bacterial architecture.

Compared to 2003 data the ESBL prevalence in Denmark has increased significantly. In the ESBL-producers, reduced susceptibility towards both gentamicin and ciprofloxacin was seen among 43% E. coli and 55% K. pneumoniae, leaving clinicians in these cases with only a carbapenem for the treatment of serious infections. Part of this study was presented at the 20(th) European Congress of Clinical Microbiology and Infectious Diseases, abstract P-1617.

The ability of different antibiotics to select for extended-spectrum ␤-lactamase (ESBL)-producing Escherichia coli remains a topic of discussion. In a mouse intestinal colonization model, we evaluated the selective abilities of nine common antimicrobials (cefotaxime, cefuroxime, dicloxacillin, clindamycin, penicillin, ampicillin, meropenem, ciprofloxacin, and amdinocillin) against a CTX-M-15-producing E. coli sequence type 131 (ST131) isolate with a fluoroquinolone resistance phenotype. Mice (8 per group) were orogastrically administered 0.25 ml saline with 10 8 CFU/ml E. coli ST131. On that same day, antibiotic treatment was initiated and given subcutaneously once a day for three consecutive days. CFU of E. coli ST131, Bacteroides, and Gram-positive aerobic bacteria in fecal samples were studied, with intervals, until day 8. Bacteroides was used as an indicator organism for impact on the Gram-negative anaerobic population. For three antibiotics, prolonged colonization was investigated with additional fecal CFU counts determined on days 10 and 14 (cefotaxime, dicloxacillin, and clindamycin). Three antibiotics (cefotaxime, dicloxacillin, and clindamycin) promoted overgrowth of E. coli ST131 (P < 0.05). Of these, only clindamycin suppressed Bacteroides, while the remaining two antibiotics had no negative impact on Bacteroides or Gram-positive organisms. Only clindamycin treatment resulted in prolonged colonization. The remaining six antibiotics, including ciprofloxacin, did not promote overgrowth of E. coli ST131 (P > 0.95), nor did they suppress Bacteroides or Gram-positive organisms. The results showed that antimicrobials both with and without an impact on Gram-negative anaerobes can select for ESBL-producing E. coli, indicating that not only Gram-negative anaerobes have a role in upholding colonization resistance. Other, so-far-unknown bacterial populations must be of importance for preventing colonization by incoming E. coli.

Studies on human and mouse gastrointestinal microbiota have correlated the composition of the microbiota to a variety of diseases, as well as proved it vital to prevent colonization with resistant bacteria, a phenomenon known as colonization resistance. Antibiotics dramatically modify the gut community and there are examples of how antibiotic usage lead to colonization with resistant bacteria [e.g., dicloxacillin usage selecting for ESBL-producing E. coli carriage], as shown by Hertz et al. Here, we investigated the impact of five antibiotics [cefotaxime, cefuroxime, dicloxacillin, clindamycin, and ciprofloxacin] on the intestinal microbiota in mice. Five different antibiotics were each given to groups of five mice. The intestinal microbiotas were profiled by use of the IS-pro analysis; a 16S–23S rDNA interspace [IS]-region-based profiling method. For the mice receiving dicloxacillin and clindamycin, we observed dramatic shifts in dominating phyla from day 1 to day 5. Of note, diversity increased, but overall bacterial load decreased. For ciprofloxacin, cefotaxime, and cefuroxime there were few overall changes. We speculate that antibiotics with efficacy against the abundant anaerobes in the gut, particularly Bacteroidetes, can in fact be selected for resistant bacteria, disregarding the spectrum of activity.

Background To investigate if a 5-day course pivmecillinam (amdinocillin pivoxil) 400 mg three times daily is superior to a 3-day course in women with uncomplicated urinary tract infection (UTI). Methods A randomised, double-blind, placebo-controlled trial conducted at nine primary care centres in Denmark. 368 women (18–70 years) with symptoms compatible with UTI were randomised to blinded therapy of 5 days [5d] or 3 days followed by 2 days of placebo [3d] from May 2015 to November 2017. Clinical data were assessed using a validated questionnaire at inclusion (day-0), daily the following 7 days and once again within the 2nd to 6th week after intervention. Bacteriological data were collected prior to intervention and twice between day 7 and 42. Main clinical endpoints were days to symptom resolution within 7 days after inclusion and proportions with clinical success at the end of intervention. Main bacteriological endpoint was proportion of participants with significant reduction of bacteriuria (≥ 10 2 CFU/mL) in 1st control urine sample. ClinicalTrialsRegister.eu: 2014–001321-32. Findings 180 (5d) and 188 (3d) participants were included in the study (mean age: 35.4 [5d] and 34.9 [3d]). Of these, 125 (70% [5d]) and 122 (66% [3d]) had a positive baseline urine culture. Forty-four participants were lost to follow-up, leaving 161 [5d] and 163 [3d] participants for analysis, respectively. Mean time to symptom resolution was 2.91 (SD 1.46; [5d]) days and 2.94 (SD 1.42; [3d]) days (P = .894). Clinical success at the end of treatment occurred for 117 of 153 (76%) receiving the 5d-course and for 115 of 157 (73%) receiving the 3d course (difference 3.2% [95% CI -7.1% - 13.5%]; P = .601). Bacteriological success was seen in 92 of 104 (88%) participants given the 5d course and in 86 of 99 (87%) given the 3d course (difference 1.6% [95% CI -8.4%-11.6%]; P = .895). Interpretations A 5-day course of pivmecillinam was not superior to a 3-day course in clinical or bacteriological outcomes for UTI. Primary funding source The Danish Regions [no. 14/217].

The worldwide increase in infections caused by extended‐spectrum beta‐lactamase‐ (ESBL) and AmpC‐producing Enterobacteriaceae (ESBL‐E) is a concern. Surveillance is extensive in Europe, North America, and Asia. Yet, there is no summarizing surveillance in Africa. This study aimed to perform a preliminary investigation on the prevalence of ESBL‐E in the northeastern part of Nigeria. However, of the 60 samples collected, we were able to culture 15 Escherichia coli and 7 Klebsiella spp. only. In the collection of clinical hospital samples, we found eight of 15 E. coli isolates to be ESBL (53%) and two out of seven Klebsiella spp. to be ESBL/AmpC (29%). Due to the limitations of this study, our findings cannot take a broad view on the prevalence of ESBL‐E, in Nigeria and other parts of Africa. Yet, to know which genes encode ESBL in Nigeria, and to know exact prevalence of every ESBL gene would be of importance.