Improving timelines in reporting results from positive blood cultures: simulation of impact of rapid identification on therapy on a real-life cohort.

For patients with bloodstream infections, rapid initiation of the appropriate antimicrobial therapy is essential in reducing mortality and morbidity. New developments and automation in clinical microbiology labs speed up the identification and susceptibility results but are expensive. To gain insight in the added value of the new workflows, we simulated the possible impact of rapid identification and susceptibility tests on a real-life cohort of 158 positive blood culture episodes. Our routine workflow was theoretically challenged against two new workflows, one based on rapid identification with MALDI-TOF MS and one based on molecular testing. First, we observed an important role of the rapid communication of the gram stain results, as about one third of patients needed an adaptation of the antimicrobial therapy based on these results. Antibiotic adaptation based on the microorganism identification was necessary in 10% and in another 25% of cases after the availability of the susceptibility results. The added value of the newer workflow methods lies mainly in the field of the rapid identification and was rather limited in our cohort. In conclusion, for optimizing the blood culture workflow, each microbiology lab should critically scan its own workflow and know its own blood culture epidemiology, before investing in expensive or time-consuming processes.

A complete and multifaceted overview of antibiotic use and infection diagnosis in the intensive care unit: results from a prospective four-year registration.

BACKGROUND: Preparing an antibiotic stewardship program requires detailed information on overall antibiotic use, prescription indication and ecology. However, longitudinal data of this kind are scarce. Computerization of the patient chart has offered the potential to collect complete data of high resolution. To gain insight in our global antibiotic use, we aimed to explore antibiotic prescription in our intensive care unit (ICU) from various angles over a prolonged time period. METHODS: We studied all adult patients admitted to Ghent University Hospital ICU from 1 January 2013 until 31 December 2016. Antibiotic prescription data were prospectively merged with diagnostic (suspected focus, severity and probability of infection at the time of prescription, or prophylaxis) and microbiology data by ICU physicians during daily workflow through dedicated software. Definite focus of infection and probability of infection (classified as high/moderate/low) were reassessed by dedicated ICU physicians at patient discharge. RESULTS: During the study period, 8763 patients were admitted and overall antibiotic consumption amounted to 1232 days of therapy (DOT)/1000 patient days. Antibacterial DOT (84% of total DOT) were linked with infection in 80%; the predominant foci were the respiratory tract (49%) and the abdomen (19%). A microbial cause was identified in 56% (3169/5686). Moderate/low probability infections accounted for 42% of antibacterial DOT prescribed for respiratory tract infections; for abdominal infections, this figure was 15%. The median treatment duration of moderate/low probability respiratory infections was 4 days (IQR 3-7). Antifungal DOT (16% of total DOT) were linked with infection in 47% of total antifungal DOT. Antifungal prophylaxis was primarily administered in the surgical ICU (76%), with a median duration of 4 DOT (IQR 2-9). CONCLUSIONS: By prospectively combining antibiotic, microbiology and clinical data we were able to construct a longitudinal, multifaceted dataset on antibiotic use and infection diagnosis. A complete overview of this kind may allow the identification of antibiotic prescription patterns that require future antibiotic stewardship attention.

Disseminated infection with Mycobacterium tilburgii in a male immunocompromised patient.

Mycobacterium tilburgii is a nonculturable nontuberculous mycobacterium identifiable only by molecular methods. We report a case of disseminated M. tilburgii infection illustrating the importance of 16S rRNA gene sequencing to determine the responsible mycobacterial pathogen and the difficulties in tailoring antimycobacterial treatment in the absence of a culturable organism.

Fourth Belgian multicentre survey of antibiotic susceptibility of anaerobic bacteria.

OBJECTIVES: To collect recent data on the susceptibility of anaerobes to antimicrobial agents with known activity against anaerobes, and to compare them with results from previous Belgian multicentre studies. METHODS: Four hundred and three strict anaerobic clinical isolates were prospectively collected from February 2011 to April 2012 in eight Belgian university hospitals. MICs were determined by one central laboratory for 11 antimicrobial agents using Etest methodology. RESULTS: According to EUCAST breakpoints, >90% of isolates were susceptible to amoxicillin/clavulanate (94%), piperacillin/tazobactam (91%), meropenem (96%), metronidazole (92%) and chloramphenicol (98%), but only 70% and 40% to clindamycin and penicillin, respectively. At CLSI recommended breakpoints, only 71% were susceptible to moxifloxacin and 79% to cefoxitin. MIC50/MIC90 values for linezolid and for tigecycline were 1/4 and 0.5/4 mg/L, respectively. When compared with survey data from 2004, no major differences in susceptibility profiles were noticed. However, the susceptibility of Prevotella spp. and other Gram-negative bacilli to clindamycin decreased from 91% in 1993-94 and 82% in 2004 to 69% in this survey. Furthermore, the susceptibility of clostridia to moxifloxacin decreased from 88% in 2004 to 66% in 2011-12 and that of fusobacteria from 90% to 71%. CONCLUSIONS: Compared with previous surveys, little evolution was seen in susceptibility, except a decline in activity of clindamycin against Prevotella spp. and other Gram-negative bacteria, and of moxifloxacin against clostridia. Since resistance was detected to all antibiotics, susceptibility testing of anaerobic isolates is indicated in severe infections to confirm appropriateness of antimicrobial therapy.

Development of antibiotic treatment algorithms based on local ecology and respiratory surveillance cultures to restrict the use of broad-spectrum antimicrobial drugs in the treatment of hospital-acquired pneumonia in the intensive care unit: a retrospective analysis.

INTRODUCTION: Timely administration of appropriate antibiotic therapy has been shown to improve outcome in hospital-acquired pneumonia (HAP). Empirical treatment guidelines tailored to local ecology have been advocated in antibiotic stewardship programs. We compared a local ecology based algorithm (LEBA) to a surveillance culture based algorithm (SCBA) in terms of appropriate coverage and spectrum of antimicrobial activity. METHODS: We retrospectively assessed 2 hypothetical empirical antibiotic treatment algorithms for HAP on an existing high-quality prospectively collected database in a mixed 36-bed tertiary intensive care unit (ICU). Data on consecutive episodes of microbiologically confirmed HAP were collected over a period of 40 months and divided in a derivation (1 July 2009 to 31 October 2010) and validation (1 November 2010 until 31 October 2012) cohort. On the derivation cohort we constructed a LEBA, based on overall observed bacterial resistance patterns, and a SCBA, which targeted therapy to surveillance culture (SC) in the individual patient. Therapy was directed against pathogens found in respiratory SC collected two to five days before HAP, and in the absence of these, presence or absence of multi-drug resistant (MDR) pathogens in other SC dictated broad-spectrum, respectively narrow spectrum antibiotic therapy. Subsequently, LEBA and SCBA were retrospectively reviewed and compared with actually prescribed antibiotics in the validation cohort. RESULTS: The first 100 HAP episodes made up the derivation cohort and the subsequent 113 HAP episodes the validation cohort. Appropriate antibiotic coverage rates by applying LEBA and SCBA were 88.5% and 87.6%, respectively, and did not differ significantly with respect to appropriateness of the actually prescribed initial therapy (84.1%). SCBA proposed more narrow spectrum therapy as compared to LEBA and the actually prescribed antimicrobials (P <0.001). SCBA recommended significantly less combination therapy and carbapenems compared to LEBA (P <0.001). SCBA targeted antibiotics to recent respiratory SC in 38.1% (43 out of 113 episodes) of HAP; in these cases adequacy was 93% (40 out of 43). CONCLUSION: Rates of appropriate antimicrobial coverage were identical in LEBA and SCBA. However, in this setting of moderate MDR prevalence, the use of SCBA would result in a significant reduction of the use of broad-spectrum drugs and may be a preferential strategy when implementing antibiotic stewardship programs.

Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial.

BACKGROUND: Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases may benefit from macrolides. METHODS: We performed a randomised double-blind placebo-controlled trial in subjects with exacerbation-prone severe asthma. Subjects received low-dose azithromycin (n=55) or placebo (n=54) as add-on treatment to combination therapy of inhaled corticosteroids and long-acting ß2 agonists for 6 months. The primary outcome was the rate of severe exacerbations and LRTI requiring treatment with antibiotics during the 26-week treatment phase. Secondary efficacy outcomes included lung function and scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ). RESULTS: The rate of primary endpoints (PEPs) during 6 months was not significantly different between the two treatment groups: 0.75 PEPs (95% CI 0.55 to 1.01) per subject in the azithromycin group versus 0.81 PEPs (95% CI 0.61 to 1.09) in the placebo group (p=0.682). In a predefined subgroup analysis according to the inflammatory phenotype, azithromycin was associated with a significantly lower PEP rate than placebo in subjects with non-eosinophilic severe asthma (blood eosinophilia ≤200/µl): 0.44 PEPs (95% CI 0.25 to 0.78) versus 1.03 PEPs (95% CI 0.72 to 1.48) (p=0.013). Azithromycin significantly improved the AQLQ score but there were no significant between-group differences in the ACQ score or lung function. Azithromycin was well tolerated, but was associated with increased oropharyngeal carriage of macrolide-resistant streptococci. CONCLUSIONS: Azithromycin did not reduce the rate of severe exacerbations and LRTI in patients with severe asthma. However, the significant reduction in the PEP rate in azithromycin-treated patients with non-eosinophilic severe asthma warrants further study. CLINICALTRIALS.GOV NUMBER: NCT00760838.

Chlamydia trachomatis infection in fertile and subfertile women in Rwanda: prevalence and diagnostic significance of IgG and IgA antibodies testing.

BACKGROUND: In many developing countries, little is known about the prevalence of genital Chlamydia trachomatis infections and complications, such as infertility, thus preventing any policy from being formulated regarding screening for C. trachomatis of patients at risk for infertility. The objective of the present study was to determine the prevalence of C. trachomatis and evaluate the diagnostic utility of serological markers namely anti-C. trachomatis IgG and IgA antibodies in women attending an infertility clinic. METHODS: Serum and vaginal swab specimens of 303 women presenting with infertility to the infertility clinic of the Kigali University Teaching Hospital and 312 fertile controls who recently delivered were investigated. Two commercial species-specific ELISA were used to determine serum IgG and IgA antibodies to C. trachomatis and vaginal swabs specimens were tested by PCR. Hysterosalpingography (HSG) was performed in subfertile women. RESULTS: The PCR prevalence of C. trachomatis infection was relatively low and did not differ significantly among subfertile and fertile women (3.3 versus 3.8%). Similarly, no significant differences in overall prevalence rates of C. trachomatis IgG and IgA among both groups were observed. The only factor associated with C. trachomatis infection in our study population was age <25 years. The seroprevalence of IgG in both assays (86.4% for ANILabsystems and 90.9% for Vircell) was significantly higher in the group of PCR C. trachomatis-positive women compared with that of PCR-negative women. Evidence of tubal pathology identified by HSG was found in 185 patients in the subfertile group (67.8%). All the serological markers measured in this study had very low sensitivities and negative predictive values in predicting tubal pathology. The specificities for ANILabsystems IgG, Vircell IgG, Anilabsystem IgA and positive C. trachomatis DNA to predict tubal pathology were 84, 86, 95 and 98%, respectively, whereas their respective positive predictive values were 73, 76, 81 and 80%. CONCLUSIONS: The prevalence of C. trachomatis in our study population in Rwanda appears to be low and women aged <25 years are more likely to have genital infection with C. trachomatis. Since serological testing for Chlamydia shows an excellent negative predictive value for lower genital tract infection, specific peptide-based serological assays may be of use for screening in low prevalence settings. Our data suggest that C. trachomatis is not the primary pathogen responsible for tubal pathology in Rwandan women.

Prevalence, risk factors and adverse pregnancy outcomes of second trimester bacterial vaginosis among pregnant women in Bukavu, Democratic Republic of the Congo.

BACKGROUND: Bacterial vaginosis (BV) is the most common gynecological condition in women of reproductive age and associated with adverse pregnancy outcomes. In the Democratic Republic of the Congo (DRC), neonatal mortality rate is as high as 2.8 percent with preterm birth (PTB) and low birth weight (LBW) as leading causes. Because no studies have addressed BV in DRC, we aimed to investigate the prevalence of BV, the risk factors and the association between BV and adverse pregnancy outcomes in a population of pregnant women from Bukavu, DRC. METHODS: A total of 533 pregnant women in the second trimester of pregnancy were recruited in the Provincial Reference Hospital of Bukavu, DRC, between January and October 2017, and followed until delivery. Clinical and sociodemographic data of mother and newborn, and data on (vaginal) hygiene practices, sexual behavior and reproductive history were collected. BV was diagnosed by Nugent scoring of Gram-stained vaginal smears. Two multivariate regression models were built to identify risk factors for BV and to investigate BV as a risk factor for adverse pregnancy outcomes. RESULTS: The prevalence of BV was 26.3% and approximately half of the women with BV were asymptomatic. Independent risk factors for BV were the use of alternatives to water for intravaginal washing, concurrent partners, unemployed status, the presence of vaginal Candida and clay consumption. BV was independently associated with both LBW and PTB of an infant with LBW. CONCLUSION: The prevalence of BV in Bukavu is high but in line with the global average. BV was associated with adverse pregnancy outcomes in our study population. Hence, research on modifiable risk factor-based interventions to reduce the prevalence of BV, and on screening/treatment of BV during antenatal care should be explored to reduce neonatal mortality and morbidity.

Comparison of different sampling techniques and of different culture methods for detection of group B streptococcus carriage in pregnant women.

BACKGROUND: Streptococcus agalactiae (group B streptococcus; GBS) is a significant cause of perinatal and neonatal infections worldwide. To detect GBS colonization in pregnant women, the CDC recommends isolation of the bacterium from vaginal and anorectal swab samples by growth in a selective enrichment medium, such as Lim broth (Todd-Hewitt broth supplemented with selective antibiotics), followed by subculture on sheep blood agar. However, this procedure may require 48 h to complete. We compared different sampling and culture techniques for the detection of GBS. METHODS: A total of 300 swabs was taken from 100 pregnant women at 35-37 weeks of gestation. For each subject, one rectovaginal, one vaginal and one rectal ESwab were collected. Plating onto Columbia CNA agar (CNA), group B streptococcus differential agar (GBSDA) (Granada Medium) and chromID Strepto B agar (CA), with and without Lim broth enrichment, were compared. The isolates were confirmed as S. agalactiae using the CAMP test on blood agar and by molecular identification with tDNA-PCR or by 16S rRNA gene sequence determination. RESULTS: The overall GBS colonization rate was 22%. GBS positivity for rectovaginal sampling (100%) was significantly higher than detection on the basis of vaginal sampling (50%), but not significantly higher than for rectal sampling (82%). Direct plating of the rectovaginal swab on CNA, GBSDA and CA resulted in detection of 59, 91 and 95% of the carriers, respectively, whereas subculturing of Lim broth yielded 77, 95 and 100% positivity, respectively. Lim broth enrichment enabled the detection of only one additional GBS positive subject. There was no significant difference between GBSDA and CA, whereas both were more sensitive than CNA. Direct culture onto GBSDA or CA (91 and 95%) detected more carriers than Lim broth enrichment and subculture onto CNA (77%). One false negative isolate was observed on GBSDA, and three false positives on CA. CONCLUSIONS: In conclusion, rectovaginal sampling increased the number GBS positive women detected, compared to vaginal and/or rectal sampling. Direct plating on CA and/or GBSDA provided rapid detection of GBS that was at least as sensitive and specific as the CDC recommended method of Lim broth subcultured onto non chromogenic agar.

Longitudinal analysis of the vaginal microflora in pregnancy suggests that L. crispatus promotes the stability of the normal vaginal microflora and that L. gasseri and/or L. iners are more conducive to the occurrence of abnormal vaginal microflora.

BACKGROUND: Despite their antimicrobial potential, vaginal lactobacilli often fail to retain dominance, resulting in overgrowth of the vagina by other bacteria, as observed with bacterial vaginosis. It remains elusive however to what extent interindividual differences in vaginal Lactobacillus community composition determine the stability of this microflora. In a prospective cohort of pregnant women we studied the stability of the normal vaginal microflora (assessed on Gram stain) as a function of the presence of the vaginal Lactobacillus index species (determined through culture and molecular analysis with tRFLP). RESULTS: From 100 consecutive Caucasian women vaginal swabs were obtained at mean gestational ages of 8.6 (SD 1.4), 21.2 (SD 1.3), and 32.4 (SD 1.7) weeks, respectively. Based on Gram stain, 77 women had normal or Lactobacillus-dominated vaginal microflora (VMF) during the first trimester, of which 18 had grade Ia (L. crispatus cell morphotypes) VMF (23.4%), 16 grade Iab (L. crispatus and other Lactobacillus cell morphotypes) VMF (20.8%), and 43 grade Ib (non-L. crispatus cell morphotypes) VMF (55.8%). Thirteen women with normal VMF at baseline, converted in the second or third trimester (16.9%) to abnormal VMF defined as VMF dominated by non-Lactobacillus bacteria. Compared to grade Ia and grade Iab VMF, grade Ib VMF were 10 times (RR = 9.49, 95% CI 1.30 - 69.40) more likely to convert from normal to abnormal VMF (p = 0.009). This was explained by the observation that normal VMF comprising L. gasseri/iners incurred a ten-fold increased risk of conversion to abnormal VMF relative to non-L. gasseri/iners VMF (RR 10.41, 95% CI 1.39-78.12, p = 0.008), whereas normal VMF comprising L. crispatus had a five-fold decreased risk of conversion to abnormal VMF relative to non-L. crispatus VMF (RR 0.20, 95% CI 0.05-0.89, p = 0.04). CONCLUSION: The presence of different Lactobacillus species with the normal vaginal microflora is a major determinant to the stability of this microflora in pregnancy: L. crispatus promotes the stability of the normal vaginal microflora while L. gasseri and/or L. iners predispose to some extent to the occurrence of abnormal vaginal microflora.

Microflora of the penile skin-lined neovagina of transsexual women.

BACKGROUND: The microflora of the penile skin-lined neovagina in male-to-female transsexuals is a recently created microbial niche which thus far has been characterized only to a very limited extent. Yet the knowledge of this microflora can be considered as essential to the follow-up of transsexual women. The primary objective of this study was to map the neo-vaginal microflora in a group of 50 transsexual women for whom a neovagina was constructed by means of the inverted penile skin flap technique. Secondary objectives were to describe possible correlations of this microflora with multiple patients' characteristics, such as sexual orientation, the incidence of vaginal irritation and malodorous vaginal discharge. RESULTS: Based on Gram stain the majority of smears revealed a mixed microflora that had some similarity with bacterial vaginosis (BV) microflora and that contained various amounts of cocci, polymorphous Gram-negative and Gram-positive rods, often with fusiform and comma-shaped rods, and sometimes even with spirochetes. Candida cells were not seen in any of the smears. On average 8.6 species were cultured per woman. The species most often found were: Staphylococcus epidermidis, Streptococcus anginosus group spp., Enterococcus faecalis, Corynebacterium sp., Mobiluncus curtisii and Bacteroides ureolyticus. Lactobacilli were found in only one of 30 women. There was no correlation between dilatation habits, having coitus, rinsing habits and malodorous vaginal discharge on the one hand and the presence of a particular species on the other. There was however a highly significant correlation between the presence of E. faecalis on the one hand and sexual orientation and coitus on the other (p = 0.003 and p = 0.027 respectively). Respectively 82%, 58% and 30% of the samples showed an amplicon after amplification with M. curtisii, Atopobium vaginae and Gardnerella vaginalis primer sets. CONCLUSION: Our study is the first to describe the microflora of the penile skin-lined neovagina of transsexual women. It reveals a mixed microflora of aerobe and anaerobe species usually found either on the skin, in the intestinal microflora or in a BV microflora.

Genotyping of Streptococcus agalactiae (group B streptococci) isolated from vaginal and rectal swabs of women at 35-37 weeks of pregnancy.

BACKGROUND: Group B streptococci (GBS), or Streptococcus agalactiae, are the leading bacterial cause of meningitis and bacterial sepsis in newborns. Here we compared different culture media for GBS detection and we compared the occurrence of different genotypes and serotypes of GBS isolates from the vagina and rectum. METHODS: Streptococcus agalactiae was cultured separately from both rectum and vagina, for a total of 150 pregnant women, i) directly onto Columbia CNA agar, or indirectly onto ii) Granada agar resp. iii) Columbia CNA agar, after overnight incubation in Lim broth. RESULTS: Thirty six women (24%) were colonized by GBS. Of these, 19 harbored GBS in both rectum and vagina, 9 only in the vagina and 8 exclusively in the rectum. The combination of Lim broth and subculture on Granada agar was the only culture method that detected all GBS positive women. Using RAPD-analysis, a total of 66 genotypes could be established among the 118 isolates from 32 women for which fingerprinting was carried out. Up to 4 different genotypes in total (rectal + vaginal) were found for 4 women, one woman carried 3 different genotypes vaginally and 14 women carried two 2 different genotypes vaginally. Only two subjects were found to carry strains with the same genotype, although the serotype of both of these strains was different.Eighteen of the 19 subjects with GBS at both sites had at least one vaginal and one rectal isolate with the same genotype.We report the presence of two to four different genotypes in 22 (61%) of the 36 GBS positive women and the presence of identical genotypes in both sites for all women but one. CONCLUSION: The combination of Lim broth and subculture on Granada medium provide high sensitivity for GBS detection from vaginal and rectal swabs from pregnant women. We established a higher genotypic diversity per individual than other studies, with up to four different genotypes among a maximum of 6 isolates per individual picked. Still, 18 of the 19 women with GBS from both rectum and vagina had at least one isolate from each sampling site with the same genotype.

Identification and genotyping of bacteria from paired vaginal and rectal samples from pregnant women indicates similarity between vaginal and rectal microflora.

BACKGROUND: The vaginal microflora is important for maintaining vaginal health and preventing infections of the reproductive tract. The rectum has been suggested as the major source for the colonisation of the vaginal econiche. METHODS: To establish whether the rectum can serve as a possible bacterial reservoir for colonisation of the vaginal econiche, we cultured vaginal and rectal specimens from pregnant women at 35-37 weeks of gestation, identified the isolates to the species level with tRNA intergenic length polymorphism analysis (tDNA-PCR) and genotyped the isolates for those subjects from which the same species was isolated simultaneously vaginally and rectally, by RAPD-analysis.One vaginal and one rectal swab were collected from a total of each of 132 pregnant women at 35-37 weeks of gestation. Swabs were cultured on Columbia CNA agar and MRS agar. For each subject 4 colonies were selected for each of both sites, i.e. 8 colonies in total. RESULTS: Among the 844 isolates that could be identified by tDNA-PCR, a total of 63 bacterial species were present, 9 (14%) only vaginally, 26 (41%) only rectally, and 28 (44%) in both vagina and rectum. A total of 121 (91.6%) of 132 vaginal samples and 51 (38.6%) of 132 rectal samples were positive for lactobacilli. L. crispatus was the most frequently isolated Lactobacillus species from the vagina (40% of the subjects were positive), followed by L. jensenii (32%), L. gasseri (30%) and L. iners (11%). L. gasseri was the most frequently isolated Lactobacillus species from the rectum (15%), followed by L. jensenii (12%), L. crispatus (11%) and L. iners (2%).A total of 47 pregnant women carried the same species vaginally and rectally. This resulted in 50 vaginal/rectal pairs of the same species, for a total of eight different species. For 34 of the 50 species pairs (68%), isolates with the same genotype were present vaginally and rectally and a high level of genotypic diversity within species per subject was also established. CONCLUSION: It can be concluded that there is a certain degree of correspondence between the vaginal and rectal microflora, not only with regard to species composition but also with regard to strain identity between vaginal and rectal isolates.These results support the hypothesis that the rectal microflora serves as a reservoir for colonisation of the vaginal econiche.

Modified classification of Gram-stained vaginal smears to predict spontaneous preterm birth: a prospective cohort study.

OBJECTIVE: The purpose of this study was to identify women at risk of spontaneous preterm birth through a 4-category Gram-stained vaginal smear method, not restricted to bacterial vaginosis. STUDY DESIGN: This was a prospective cohort study correlating Gram-stained vaginal smears in early pregnancy with spontaneous preterm birth. Smears were categorized as 'normal,' 'bacterial vaginosis-like,' 'grade I-like' (atypical gram-positive rods) or 'purulent grade I' (lactobacilli-dominated smears showing heavy leukorrhea of unknown cause). RESULTS: Normal microflora were associated with a 4-fold decreased risk (95%CI 0.1-0.6, P < .001) of spontaneous preterm birth and an abnormal Gram stain with an overall adjusted odds ratio of 5.2 (95%CI 1.8-14.5, P < .001). The sensitivity of vaginal smear diagnosis for preterm birth increased from 25% with conventional scoring up to 70% with these modified criteria. CONCLUSION: Accounting for atypical gram-positive bacteria and neutrophils on Gram-stained vaginal smears may identify a larger proportion of women at risk of preterm birth compared to diagnosis of bacterial vaginosis alone.

Three cases of OXA-48-like carbapenemase producing Enterobacteriaceae (not) detected using Xpert® Carba-R.

The increasing prevalence of carbapenemase-producing Enterobacteriaceae necessitates laboratories to invest in the detection of these bacteria, both with phenotypic and to a lesser extent molecular methods. OXA-48-like strains are rapidly emerging, especially in Europe. Since the expression level of OXA-48 is low and some strains present with several alleles, some types might be missed by some molecular assays. Three cases of OXA-48-like strains are described here, where the detection was not straightforward.

Contamination risk of synovial biopsy cultures in total hip arthroplasty: a prospective review of 100 cases.

INTRODUCTION: Cultures of deep synovial biopsies remain an important tool in diagnosing periprosthetic joint infection, a devastating complication following total hip arthroplasty (THA). Recent reports of unexpected positive intraoperative cultures in aseptic revision arthroplasty, however, challenge the validity and interpretation of these cultures. The aim of this study was to evaluate the contamination risk of synovial biopsy cultures collected intraoperatively during primary THA of healthy subjects. METHODS: Synovial biopsies for culture were collected during primary total hip arthroplasty procedures from 100 consecutive cases. The synovial biopsies were taken within the first 15 minutes after skin incision. Biopsy specimen were cultured on 4 different media for 8 or 15 days. Positive cultures were identified using Maldi-Tof spectrometry. RESULTS: 16 cultures yielded a bacterium, suggesting a false positive result of 16%. The mean time for the cultures to become positive was 6.29 days (standard deviation [SD] 3.90) with a maximum of 15 days. Proprionibacterium acnes and Staphylococcus epidermidis were most commonly cultured with 6 positive results for both bacteria. CONCLUSIONS: Our study yielded a 16% false positive rate in cultures of synovial biopsy taken during primary total hip arthroplasty of healthy subjects, suggesting that contamination risk of these synovial biopsy cultures may be larger than assumed by clinicians.

Outcome in bacteremia associated with nosocomial pneumonia and the impact of pathogen prediction by tracheal surveillance cultures.

OBJECTIVE: To assess whether pathogen prediction in bacteremia associated with nosocomial pneumonia (NP) by tracheal surveillance cultures improves adequacy of early antibiotic therapy and impacts mortality. DESIGN AND SETTING: A retrospective observational study of a prospectively gathered cohort. This cohort included all adult patients admitted to the ICU of a tertiary care hospital from 1992 through 2001 and who developed bacteremia associated with NP. MEASUREMENTS AND MAIN RESULTS: 128 episodes of bacteremia associated with NP were identified. In 110 episodes a tracheal surveillance culture 48-96h prior to bacteremia was available: this culture predicted the pathogen in 67 episodes (61%). Overall rates of appropriate empiric antibiotic therapy within 24 and 48h were 62 and 87%, respectively. Pathogen prediction was associated with a significantly higher rate of appropriate antibiotic therapy within 24h (71 vs 45%; p=0.01), but not within 48h (91 vs 82%; p=0.15). Crude in-hospital mortality was 50%. Pathogen prediction was associated with increased survival in univariate (OR 0.43; CI 0.19-0.93; p=0.04) and multivariate analysis (OR 0.32; CI 0.12-0.82; p=0.02). Multivariate analysis further identified age (OR 1.04; CI 1.01-1.07; p=0.02), increasing APACHEII score (OR 1.08; CI 1.02-1.15; p=0.01), and methicillin-resistant Staphylococcus aureus (OR 5.90; CI 1.36-25.36; p=0.01) and Pseudomonas aeruginosa (OR 3.30; CI 1.04-10.4; p=0.04) as independent risk factors for mortality. CONCLUSION: Pathogen prediction in bacteremia associated with NP by tracheal surveillance cultures is associated with a higher rate of adequate empiric antibiotic therapy within 24[Symbol: see text]h and with increased survival.

Antibiotic susceptibility of Atopobium vaginae.

BACKGROUND: Previous studies have indicated that a recently described anaerobic bacterium, Atopobium vaginae is associated with bacterial vaginosis (BV). Thus far the four isolates of this fastidious micro-organism were found to be highly resistant to metronidazole and susceptible for clindamycin, two antibiotics preferred for the treatment of BV. METHODS: Nine strains of Atopobium vaginae, four strains of Gardnerella vaginalis, two strains of Lactobacillus iners and one strain each of Bifidobacterium breve, B. longum, L. crispatus, L. gasseri and L. jensenii were tested against 15 antimicrobial agents using the Etest. RESULTS: All nine strains of A. vaginae were highly resistant to nalidixic acid and colistin while being inhibited by low concentrations of clindamycin (range: < 0.016 microg/ml), rifampicin (< 0.002 microg/ml), azithromycin (< 0.016-0.32 microg/ml), penicillin (0.008-0.25 microg/ml), ampicillin (< 0.016-0.94 microg/ml), ciprofloxacin (0.023-0.25 microg/ml) and linezolid (0.016-0.125 microg/ml). We found a variable susceptibility for metronidazole, ranging from 2 to more than 256 microg/ml. The four G. vaginalis strains were also susceptible for clindamycin (< 0.016-0.047 microg/ml) and three strains were susceptible to less than 1 microg/ml of metronidazole. All lactobacilli were resistant to metronidazole (> 256 microg/ml) but susceptible to clindamycin (0.023-0.125 microg/ml). CONCLUSION: Clindamycin has higher activity against G. vaginalis and A. vaginae than metronidazole, but not all A. vaginae isolates are metronidazole resistant, as seemed to be a straightforward conclusion from previous studies on a more limited number of strains.

Pneumococcal conjugate vaccination in children with recurrent acute otitis media: a therapeutic alternative?

BACKGROUND: Based on two clinical trials in healthy infants the American Academy of Pediatrics (AAP) advices immunization with a 7-valent pneumococcal conjugate vaccine in children with recurrent acute otitis media (AOM). OBJECTIVE: To study the efficacy of a 7-valent pneumococcal conjugate vaccine on acute otitis media recurrences, its immunogenicity and impact on nasopharyngeal Streptococcus pneumoniae carriage in children with a history of frequent acute otitis media. METHODS: In this double-blind, randomized study, 74 Belgian children, aged 1-7 years, with at least 2 clinically diagnosed episodes of acute otitis media in the previous year were enrolled. Children were immunized with either a 7-valent pneumococcal conjugate vaccine followed by a 23-valent pneumococcal polysaccharide booster or a control hepatitis A vaccine. Total follow-up was 26 months. RESULTS: Despite adequate serum IgG responses to all conjugate vaccine pneumococcal serotypes, no reduction of acute otitis media episodes was observed in the pneumococcal vaccine group as compared to the control group (rate ratio: 1.16; 95% CI: 0.69-1.96). Overall nasopharyngeal pneumococcal carriage remained stable. However, a transient shift from conjugate vaccine related S. pneumoniae serogroups to non-vaccine related serogroups was noted following conjugate vaccination. CONCLUSION: Clinically no protective effect of pneumococcal conjugate vaccination on acute otitis media recurrences was found in children with a history of frequent AOM.

Impact of de-escalation of beta-lactam antibiotics on the emergence of antibiotic resistance in ICU patients: a retrospective observational study.

PURPOSE: Antibiotic de-escalation is promoted to limit prolonged exposure to broad-spectrum antibiotics, but proof that it prevents the emergence of resistance is lacking. We evaluated determinants of antibiotic de-escalation in an attempt to assess whether the latter is associated with a lower emergence of antimicrobial resistance. METHODS: Antibiotic treatments, starting with empirical beta-lactam prescriptions, were prospectively documented during 2013 and 2014 in a tertiary intensive care unit (ICU) and categorized as continuation, de-escalation or escalation of the empirical antimicrobial treatment. Determinants of the de-escalation or escalation treatments were identified by multivariate logistic regression; the continuation category was used as the reference group. Using systematically collected diagnostic and surveillance cultures, we estimated the cumulative incidence of antimicrobial resistance following de-escalation or continuation of therapy, with adjustment for ICU discharge and death as competing risks. RESULTS: Of 478 anti-pseudomonal antibiotic prescriptions, 42 (9 %) were classified as escalation of the antimicrobial treatment and 121 (25 %) were classified as de-escalation, mainly through replacement of the originally prescribed antibiotics with those having a narrower spectrum. In multivariate analysis, de-escalation was associated with the identification of etiologic pathogens (p < 0.001). The duration of the antibiotic course in the ICU in de-escalated versus continued prescriptions was 8 (range 6-10) versus 5 (range 4-7) days, respectively (p < 0.001). Mortality did not differ between patients in the de-escalation and continuation categories. The cumulative incidence estimates of the emergence of resistance to the initial beta-lactam antibiotic on day 14 were 30.6 and 23.5 % for de-escalation and continuation, respectively (p = 0.22). For the selection of multi-drug resistant pathogens, these values were 23.5 (de-escalation) and 18.6 % (continuation) respectively (p = 0.35). CONCLUSION: The emergence of antibiotic-resistant bacteria after exposure to anti-pseudomonal beta-lactam antibiotics was not lower following de-escalation.