Case series of carbapenemase-producing Enterobacteriaceae osteomyelitis: Feel it in your bones.

OBJECTIVES: Limited data have been reported regarding osteomyelitis due to carbapenemase-producing Enterobacteriaceae (CPE), including co-infections with extended-spectrum ß-lactamase (ESBL)-producing micro-organisms. METHODS: We conducted a retrospective study in a reference centre for bone and joint infections from 2011 to 2019 among patients infected with CPE. RESULTS: Nine patients (mean age 46.8 ± 16.6 years), including three with infected implants, were identified. Infections were mostly polymicrobial (n = 8/9), including Staphylococcus aureus (n = 6/9). CPE were mainly OXA-48-type, associated with ESBL-producing Enterobacteriaceae (n = 8/9), of which 5/9 isolates were Klebsiella pneumoniae. Control of the infection was achieved in seven cases. CONCLUSIONS: CPE osteomyelitides are essentially polymicrobial and fluoroquinolone-resistant infections, highlighting the need for efficient surgery with implant removal.

Fecal microbiota transplantation to eradicate vancomycin-resistant enterococci colonization in case of an outbreak.

OBJECTIVE: A rapid and worrying emergence of vancomycin-resistant enterococci (VRE) gut colonization is occurring worldwide and may be responsible for outbreaks, especially in healthcare facilities. While no efficient decolonization strategies are recommended, we assessed fecal microbiota transplantation (FMT) to eradicate VRE colonization. PATIENTS AND METHOD: Our main objective was to measure the impact of FMT on decolonization of VRE carriers, confirmed by at least two consecutive negative rectal swabs at one-week interval during a 3-month follow-up period. Patients received no antibiotic prior to the FMT. RESULTS: After a month only three patients remained colonized with VRE. Decolonization was associated with 87.5% (n=7) of success after three months as only one patient remained colonized. CONCLUSION: Our first results confirm that the FMT seems to be safe, with an impact on VRE colonization over time that may help control outbreaks.

Changes in eosinophil count during bacterial infection: revisiting an old marker to assess the efficacy of antimicrobial therapy.

INTRODUCTION: Eosinopenia as a criterion of sepsis has been the subject of debate for decades. Different authors have proposed different cut-off values. METHODS: A prospective study was conducted from February to August 2016. Hospitalized adults suffering from a bacterial infection with eosinopenia, defined as an eosinophil count <100/mm3, were included. Patients were divided into two groups according to the first day of effective antimicrobial therapy. They were observed for 5days in order to evaluate whether recovery from eosinopenia was predictive of an appropriate antibiotic regimen. RESULTS: One hundred and twenty-two patients were screened and 96 were included. Group 1 patients (n=70) received effective antimicrobial therapy from day 0. Their eosinophil count increased significantly between day 0 and day 1 (p<0.0001). Group 2 patients (n=26) received delayed effective antimicrobial therapy, and there was no significant difference in eosinophil count between day 0 and day 1 (p=0.55). Moreover, eosinophil counts normalized on day 5 in both groups. The mean duration of antimicrobial therapy was comparable in the two groups (7.7±1.16 days). The antibiotics most often prescribed in both groups were intravenous cephalosporins. During follow-up, all patients were considered to be cured after day 30. CONCLUSIONS: The eosinophil count appears to normalize faster than C-reactive protein (CRP) and polymorphonuclear neutrophils in eosinopenic patients on appropriate antimicrobial therapy. This simple test is easy to perform as part of a regular complete blood count, with no additional costs as required for CRP or procalcitonin.

Non-typhi Salmonella enterica urinary tract infections.

OBJECTIVE: Non-typhi Salmonella enterica urinary tract infections (UTIs) are not frequent and rarely reported in the literature. We aimed to characterize clinical presentations and risk factors for the infection. PATIENTS AND METHODS: We performed a retrospective study of non-typhi Salmonella enterica strains isolated from urine cytobacteriological examinations (UCBE) collected between January 1, 1996 and October 30, 2014 and analyzed by the microbiology laboratories of the university hospitals of the western part of Île-de-France and of Paris, France. RESULTS: Twenty UCBEs positive for non-typhi Salmonella enterica were analyzed. The sex ratio was 0.53 and the average age of patients was 57 years. Clinical presentations were acute pyelonephritis, acute cystitis, and prostatitis. Eight cases of bacteremia were identified. Diarrhea was observed in half of patients, either before the UTI or simultaneously. No patient required to be transferred to the intensive care unit. Immunodeficiency and/or diabetes were observed in eight patients. Three patients presented with a uropathy. Prescribed antibiotics were third generation cephalosporins and fluoroquinolones. The average treatment duration was 20 days. A spondylitis and a purulent pleurisy were observed and deemed related to the UTI. Patient outcome was always favorable following treatment prescription. CONCLUSION: Non-typhi Salmonella enterica UTIs are rare. They are mainly observed in elderly patients presenting with immunodeficiency or an underlying urological disorder.

Is faecal microbiota transplantation an option to eradicate highly drug-resistant enteric bacteria carriage?

Carbapenem-resistant Enterobacteriaceae (CRE) or vancomycin-resistant enterococci (VRE) carriage present a major public health challenge. Decolonization strategies are lacking. We aimed to evaluate the impact of faecal microbiota transplantation (FMT) on a cohort of patients with digestive tract colonization by CRE or VRE. Eight patients were included: six carrying CRE and two colonized by VRE. One month after FMT, two patients were free from CRE carriage, and another patient was free from VRE after three months. In our experience, this strategy is safe.

Implementation of a simple innovative system for postprescription antibiotic review based on computerized tools with shared access.

BACKGROUND: Controlling antibiotic use in healthcare establishments limits their consumption and the emergence of bacterial resistance. AIM: To evaluate the efficiency of an innovative antibiotic stewardship strategy implemented over three years in a university hospital. METHODS: An antimicrobial multi-disciplinary team (AMT) [pharmacist, microbiologist and infectious disease specialist (IDS)] conducted a postprescription review. Specific coding of targeted antibiotics (including broad-spectrum ß-lactams, glycopeptides, lipopeptides, fluoroquinolones and carbapenems) in the computerized physician order entry allowed recording of all new prescriptions. The data [patient, antibiotic(s), prescription start date, etc.] were registered on an AMT spreadsheet with shared access, where the microbiologist's opinion on the drug choice, based on available microbiology results, was entered. When the microbiologist and pharmacist did not approve the antibiotic prescribed, a same-day alert was generated and sent to the IDS. That alert led the IDS to re-evaluate the treatment. FINDINGS: From 2012 to 2014, 2106 targeted antibiotic prescriptions were reviewed. Among them, 389 (18.5%) generated an alert and 293 (13.9%) were re-evaluated by the IDS. Recommendations (mostly de-escalation or discontinuation) were necessary for 136 (46.4%) and the prescribers' acceptance rate was 97%. The estimated intervention time was <30 min/day for each AMT member. This system allowed correct use of targeted antibiotics for 91.8% of prescriptions, but had no significant impact on targeted antibiotic consumption. CONCLUSION: This computerized, shared access, antibiotic stewardship strategy seems to be time saving, and effectively limited misuse of broad-spectrum antibiotics.

Diagnostic delay of pyogenic vertebral osteomyelitis and its associated factors.

OBJECTIVES: Pyogenic vertebral osteomyelitis (PVO) is a rare disease with possible severe complications (e.g. sepsis and spinal cord injury). In the 1990s, diagnostic delay (DD) was often extensive as PVO has a non-specific clinical spectrum, mostly afebrile with back pain, and access to magnetic resonance imaging (MRI) was not straightforward. Our aim was to perform a new study focusing on the clinical spectrum and DD of PVO and its associated factors. METHOD: This study examined a prospective cohort of 88 patients having PVO with microbiological identification between 15 November 2006 and 15 November 2010. RESULTS: The 88 patients included in the study (female:male ratio 1:8) had a mean age of 64.1 years. The mean (sd) DD was 45.5 (50.4) days (range 2-280), and 46 patients (52.2%) were febrile at diagnosis. The main microorganism involved was Staphylococcus (n = 45; 51.1%). In univariate and multivariate analyses, age > 75 years, antecedent back pain, involvement of bacteria, topography of PVO, and anti-inflammatory drug intake did not affect the DD, unlike a C-reactive protein (CRP) value > 63 mg/L or a positive blood culture (DD lowered from 73 to 17 days and from 90 to 30 days, respectively). Conversely, X-ray investigation was associated with a longer DD (from 14 to 34.7 days). Severity at diagnosis was not significantly different depending on the intake of anti-inflammatory drugs. CONCLUSIONS: Despite easier access to MRI, the DD for PVO remains long. One shortening factor is a high CRP value, which could be a useful diagnostic tool in case of back pain. Anti-inflammatory drugs seem to have no impact on DD and severity at diagnosis.

Prospective evaluation of antibiotic treatment for urological procedure in patients presenting with neurogenic bladder.

OBJECTIVES: Patients presenting with neurogenic bladder often require urological procedures (urodynamic testing and botulinum toxin injections) and a preventive antibiotic therapy. We aimed to assess the efficacy of this little known strategy in a cohort of patients. PATIENTS AND METHODS: All patients presenting with neurogenic bladder who underwent urological procedure were included in the study. They received an antibiotic therapy in accordance with the urine cytobacteriological examination results. The antibiotic therapy was initiated two days before the procedure and prolonged up until two days after the procedure if the culture was positive. Patients were treated with a single dose of fosfomycin-trometamol in case of a negative culture. The main study outcome was the occurrence of urinary tract infection (UTI), defined by a positive urine culture and symptoms, up until 14 days after the procedure. RESULTS: A total of 80 urological procedures were performed. Mean patient age was 47±13.1 years (sex ratio 1.22); 59 (73.8%) presented with asymptomatic bacteriuria before the procedure. Nine (11.1%) UTIs were recorded on Day 14, of which one (1.2%) was febrile. Two patients required an additional curative antibiotic therapy. No patient was hospitalized. Overall, 77.8% of UTIs were cured without antibiotic therapy. CONCLUSION: Screening and treating asymptomatic bacteriuria before urological procedures seems unnecessary and vainly exposes this population at high risk of infectious diseases to antibiotic therapies. This data should be confirmed by a randomized clinical trial.

Evaluating antibiotic therapies prescribed to adult patients in the emergency department.

OBJECTIVES: The proper use of antibiotics is a public health priority to preserve their effectiveness. Little data is available on outpatient antibiotic prescriptions, especially in the emergency department. We aimed to assess the quality of outpatient antibiotic prescriptions in our hospital. PATIENTS AND METHODS: Retrospective monocentric study of antibiotic prescriptions written to adult patients managed at the emergency department without hospitalization (November 15th, 2012-November 15th, 2013). Prescriptions were evaluated by an infectious disease specialist and an emergency physician on the basis of local recommendations compiled from national and international guidelines. RESULTS: A total of 760 prescriptions were reviewed. The most frequent indications were urinary tract infections (n=263; 34.6%), cutaneous infections (n=198; 26.05%), respiratory tract infections (n=101; 13.28%), and ENT infections (n=62; 8.15%). The most frequently prescribed antibiotics were fluoroquinolones (n=314; 40.83%) and amoxicillin-clavulanic acid (n=245; 31.85%). Overall, 455 prescriptions (59.86%) did not comply with guidelines. The main reasons for inadequacy were the absence of an indication for antibiotic therapy (n=197; 40.7%), an inadequate spectrum of activity, i.e. too broad, (n=95; 19.62%), and excessive treatment duration (n=87; 17.97%). Rates of inadequate prescriptions were 82.26% for ENT infections, 71.2% for cutaneous infections, 46.53% for respiratory tract infections, and 38.4% for urinary tract infections. CONCLUSION: Antibiotic prescriptions written to outpatients in the emergency department are often inadequate. Enhancing prescribers' training and handing out guidelines is therefore necessary. The quality of these prescriptions should then be re-assessed.

Serum protein electrophoresis: an interesting diagnosis tool to distinguish viral from bacterial community-acquired pneumonia.

29-69 % of pneumonias are microbiologically documented because it can be considered as an invasive procedure with variable test sensitivity. However, it drastically impacts therapeutic strategy in particular the use of antibiotics. Serum protein electrophoresis (SPEP) is a routine and non-invasive test commonly used to identify serum protein disorders. As virus and bacteria may induce different globulins production, we hypothesize that SPEP can be used as an etiological diagnosis test. Retrospective study conducted from 1/1/13 until 5/1/15 among patient hospitalized for an acute community-acquired pneumonia based on fever, crackles and radiological abnormalities. α/ß, α/γ, ß/γ globulins and albumin/globulin (A/G) ratio were calculated from SPEP. Data were analyzed in 3 groups: documented viral (DVP) or bacterial pneumonia (DBP) and supposedly bacterial pneumonia (SBP). We used ANOVA statistic test with multiple comparisons using CI95 and ROC curve to compare them. 109 patients included divided into DBP (n = 16), DVP (n = 26) and SBP (n = 67). Mean age was 62 ± 18 year-old with a sex ratio M/F of 1.3. Underlying conditions (e.g. COPD, diabetes) were comparable between groups in multivariate analysis. Means of A/G ratio were 0.80 [0.76-0.84], 0.96 [0.91-1.01], 1.08 [0.99-1.16] respectively for DBP, SBP and DVP (p = 0.0002). A/G ratio cut-off value of 0.845 has a sensitivity of 87.5 % and a specificity of 73.1 %. A/G ratio seems to be an easy diagnostic tool to differentiate bacterial from viral pneumonia. A/G ratio cut-off value below 0.845 seems to be predictable of a bacterial origin and support the use of antibiotics.

Blood stream infections due to multidrug-resistant organisms among spinal cord-injured patients, epidemiology over 16 years and associated risks: a comparative study.

STUDY DESIGN: Retrospective study. OBJECTIVES: We aimed to describe the epidemiology of multidrug-resistant organisms (MDROs) during bloodstream infection (BSI) and identify associated risks of MDROs among patients with spinal cord injury (SCI). SETTING: A teaching hospital, expert center in disability, in France. METHODS: We studied a retrospective cohort of all BSIs occurring in SCI patients hospitalized over 16 years. We described the prevalence of MDRO BSI among this population and its evolution over time and compared the BSI population due to MDROs and due to non-MDROs. RESULTS: A total of 318 BSIs occurring among 256 patients were included in the analysis. The most frequent primary sites of infection were urinary tract infection (34.0%), pressure sore (25.2%) and catheter line-associated bloodstream infection (11.3%). MDROs were responsible for 41.8% of BSIs, and this prevalence was stable over 16 years. No significant associated factor for MDRO BSI could be identified concerning sociodemographic and clinical characteristics, primary site of infection and bacterial species in univariate and multivariate analyses. BSI involving MDROs was not associated with initial severity of sepsis compared with infection without MDROs (43.8 vs 43.6%, respectively) and was not associated either with 30th-day mortality (6.2 vs 9%, respectively). CONCLUSION: During BSI occurrence in an SCI population, MDROs are frequent but remain stable over years. No associated risk can be identified that would help optimize antibiotic treatment. Neither the severity of the episode nor the mortality is significantly different when an MDRO is involved.

Chronic gonococcal arthritis with C5 deficiency presenting with brief flare-ups: case study and literature review.

Gonococcal arthritis is typically acute and appears within 3 weeks after initial infection. Chronic gonococcal arthritis is now exceptionally rare, since the advent of the antibiotic era. Numerous host factors are involved in gonococcal dissemination, such as complement deficiency, HIV and gonococcus strain characteristics. Gonococcal arthritis shares the same risk factors. In this instance, our patient was a 16-year-old girl suffering from persistent polyarthralgia with joint swelling presenting with brief flare-ups for a period of 1 year. She disclosed a single episode of unprotected sexual intercourse 1 year ago, i.e. just before developing her first rheumatological symptoms. Therefore, we performed a joint aspiration (arthrocentesis), and synovial fluid was inoculated directly into aerobic and anaerobic blood culture bottles, which tested positive for Neisseria gonorrhoeae within 24 h. Clinical presentation was consistent with previous reports of chronic gonococcal arthritis. Further investigation revealed a C5 complement deficiency, which might explain the chronic Neisseria process. A favourable outcome was reached after a ten-day course of IV ceftriaxone, with no apparent sequelae found during follow-up 6 weeks later. This case demonstrates an unusual gonococcal arthritis with brief flare-ups for the course of a year, followed by a subacute form. N. meningitidis infections, similar to N. gonorrhoeae, are typically acute and may sometimes be involved in chronic processes. However, this characteristic appears to be rare in the case of N. gonorrhoeae. Risk factors for this chronic process will be discussed with a review of the literature.

Comparison of six generic vancomycin products for treatment of methicillin-resistant Staphylococcus aureus experimental endocarditis in rabbits.

Concerns have recently emerged about the potency and the quality of generic vancomycin (VAN) products approved for use in humans, based on experiments in a neutropenic mouse thigh infection model. However, other animal models may be more appropriate to decipher the bactericidal activities of VAN generics in vivo and to predict their efficacy in humans. We aimed to compare the bactericidal activities of six generic VAN products currently used in France (Mylan and Sandoz), Spain (Hospira), Switzerland (Teva), and the United States (Akorn-Strides and American Pharmaceutical Products [APP]) in a rabbit model of aortic valve endocarditis induced by 8 × 10(7) CFU of methicillin-resistant Staphylococcus aureus (MRSA) strain COL (VAN MIC, 1.5 µg/ml). In vitro, there were no significant differences in the time-kill curve studies performed with the six generic VAN products. Ten rabbits in each group were treated with intravenous (i.v.) VAN, 60 mg/kg of body weight twice a day (b.i.d.) for 4 days. Mean peak serum VAN levels, measured 45 min after the last injection, ranged from 35.5 (APP) to 45.9 µg/ml (Teva). Mean trough serum VAN levels, measured 12 h after the last injection, ranged from 2.3 (Hospira) to 9.2 (APP) µg/ml. All generic VAN products were superior to controls (no treatment) in terms of residual organisms in vegetations (P < 0.02 for each comparison) and in the spleen (P < 0.005 for each comparison). Pairwise comparisons of generic VAN products found no significant differences. In conclusion, a stringent MRSA endocarditis model found no significant differences in the bactericidal activities of six generic VAN products currently used in Europe and America.

Severe transaminitis after interferon-ribavirin therapy in HIV/HCV-coinfected patients: influence of a sustained HCV response.

Chronic hepatitis C is an independent risk factor for severe drug hepatotoxicity. Successful treatment of chronic hepatitis C may modulate drug hepatotoxicity, as it is associated with a decline in hepatic enzyme release and halts fibrosis progression in HIV/HCV-coinfected patients. The aim of this study was to determine biological and/or clinical determinants of alanine aminotransferase and/or aspartate aminotransferase elevation (>five-fold above the upper limit of normal in patients with normal baseline levels or >3.5-fold increase from baseline in those with increased baseline levels) in a large prospective cohort of HIV/HCV-coinfected patients on HAART who had previously been treated for HCV infection. Median follow-up exceeded five years. Cox proportional hazards models were used. At baseline, 248 patients had been receiving antiretroviral therapy for a mean of 6.3 (± 3.2) years. Seventy-one patients (29%) had a sustained HCV viral response (SVR). During follow-up, 66 patients (26.6%) received a second course of HCV therapy and 29 (44%) of them had an SVR. Severe transaminitis occurred in 64 patients (26%). In multivariate analysis, no SVR (HR 33.33, 95% CI 4.54-222, P = 0.001) and stavudine-based therapy (HR 2.11, 95% CI 1.12-3.99, P = 0.018) remained significantly associated with severe transaminitis. A SVR to anti-HCV therapy is thus associated with a markedly reduced risk of severe transaminitis during antiretroviral therapy. Treatment of HCV infection should therefore be a priority in HIV-coinfected patients. Stavudine is associated with an increased risk of severe transaminitis.

Satisfaction with care in HIV-infected patients treated with long-term follow-up antiretroviral therapy: the role of social vulnerability.

The aim of this study was to determine factors associated with complete satisfaction with the care provided (satisfaction with physicians and satisfaction with services and organization) among HIV-infected patients followed up in the French ANRS CO8 APROCO-COPILOTE cohort. Analyses focused on cross-sectional data collected during the ninth year of cohort follow-up. Satisfaction with care, sociodemographic characteristics, and behavioral data were collected using self-administered questionnaires, while clinical data were derived from medical records. Complete satisfaction with care was defined as being 100% satisfied. Two logistic regression models were used to identify predictors of (1) complete satisfaction with physicians (n=404) and (2) complete satisfaction with services and organization (n=396). Sixteen percent of patients were completely satisfied with physicians, while 15.9% were completely satisfied with services and organization. Being older and reporting fewer discomforting antiretroviral therapy (ART) side effects were factors independently associated with complete satisfaction with both physicians and services and organization. Strong support from friends and absence of hepatitis C (HCV) co-infection were independently associated with complete satisfaction with physicians, while strong support from one's family and comfortable housing conditions were independently associated with complete satisfaction with services and organization. Even after nine years of follow-up, social vulnerabilities still strongly influence HIV-infected patients' interactions with the health care system. Day-to-day experience with the disease, including perceived treatment side effects, appears to play a key role in the quality of these interactions. More attention should be given to patient satisfaction, especially for socially vulnerable patients, in order to avoid potentially detrimental consequences such as poor adherence to ART.

[Genital lymphogranuloma venereum in an HIV-1 infected patient]. / Lymphogranulomatose vénérienne génitale chez un patient infecté par le VIH-1.

BACKGROUND: Lymphogranuloma venereum (LGV) is an uncommon sexually transmitted disease caused by the L serovars of Chlamydiae trachomatis. Since 2003-2004, a continued outbreak of LGV proctitis (C. trachomatis serovar L2b) has been reported in North America and Europe, including France, among homosexual males, especially with HIV co-infection. CASE REPORT: A 41-year-old man presented penile ulceration of three weeks' standing, associated with a large swollen granulomatous lesion and an inguinal lymph node but without proctitis. All lesions resolved after a three-week course of doxycycline 200mg daily. These lesions were related to a genital bubo due to LGV as confirmed by positive specific PCR for C. trachomatis (serovar L2) performed on the genital ulceration. DISCUSSION: Clinical descriptions of male genital LGV are infrequent, even during the LGV proctitis epidemic seen in Western countries in recent years. A diagnosis of LGV must be considered in the presence of sexually transmitted genital lesions, even atypical, especially among HIV-infected patients.