Invasive bone and joint infections from the French Scedosporiosis/lomentosporiosis Observational Study (SOS) cohort: no mortality with long-term antifungal treatment and surgery.

Little is known about localized osteoarticular Scedosporiosis (LOS). Most data come from case reports and small case series. Here we present an ancillary study of the nationwide French Scedosporiosis Observational Study (SOS), describing 15 consecutive cases of LOS diagnosed between January 2005 and March 2017. Adult patients diagnosed with LOS defined by osteoarticular involvement without distant foci reported in SOS were included. Fifteen LOS were analyzed. Seven patients had underlying disease. Fourteen patients had prior trauma as potential inoculation. Clinical presentation was arthritis (n = 8), osteitis (n = 5), and thoracic wall infection (n = 2). The most common clinical manifestation was pain (n = 9), followed by localized swelling (n = 7), cutaneous fistulization (n = 7), and fever (n = 5). The species involved were Scedosporium apiospermum (n = 8), S. boydii (n = 3), S. dehoogii (n = 1), and Lomentospora prolificans (n = 3). The species distribution was unremarkable except for S. boydii, which was associated with healthcare-related inoculations. Management was based on medical and surgical treatment for 13 patients. Fourteen patients received antifungal treatment for a median duration of 7 months. No patients died during follow-up. LOS exclusively occurred in the context of inoculation or systemic predisposing factors. It has a non-specific clinical presentation and is associated with an overall good clinical outcome, provided there is a prolonged course of antifungal therapy and adequate surgical management.

Localized osteoarticular scedosporiosis mostly occurs following direct inoculation. Management was most often based on voriconazole therapy and concomitant surgery. Unlike other invasive scedosporiosis, no patient died during follow-up.

The economic burden of urinary tract infections in women visiting general practices in France: a cross-sectional survey.

BACKGROUND: Urinary tract infections (UTIs) are among the most common bacterial infections. Despite this burden, there are few studies of the costs of UTIs. The objective of this study was to determine the costs of UTIs in women over 18 years of age who visit general practitioners in France. METHODS: The direct and indirect costs of clinical UTIs were estimated from societal, French National Health Insurance and patient perspectives. The study population was derived from a national cross-sectional survey entitled the Drug-Resistant Urinary Tract Infection (Druti). The Druti included every woman over 18 years of age who presented with symptoms of UTI and was conducted in France in 2012 and 2013 to estimate the annual incidence of UTIs due to antibiotic-resistant Enterobacteriaceae in women visiting general practitioners (GPs) for suspected UTIs. RESULTS: Of the 538 women included in Druti, 460 were followed over 8 weeks and included in the cost analysis. The mean age of the women was 46 years old. The median cost of care for one episode of a suspected UTI was €38, and the mean cost was €70. The annual societal cost was €58 million, and €29 million of this was reimbursed by the French National Health Insurance system. In 25 % of the cases, the suspected UTIs were associated with negative urine cultures. The societal cost of these suspected UTIs with negative urine cultures was €13.5 million. No significant difference was found between the costs of the UTIs due to antibiotic-resistant E. coli and those due to wild E. coli (p = 0.63). CONCLUSION: In the current context in which the care costs are continually increasing, the results of this study suggests that it is possible to decrease the cost of UTIs by reducing the costs of suspected UTIs and unnecessary treatments, as well as limiting the use of non-recommended tests.

Diversity, community composition, and dynamics of nonpigmented and late-pigmenting rapidly growing mycobacteria in an urban tap water production and distribution system.

Nonpigmented and late-pigmenting rapidly growing mycobacteria (RGM) have been reported to commonly colonize water production and distribution systems. However, there is little information about the nature and distribution of RGM species within the different parts of such complex networks or about their clustering into specific RGM species communities. We conducted a large-scale survey between 2007 and 2009 in the Parisian urban tap water production and distribution system. We analyzed 1,418 water samples from 36 sites, covering all production units, water storage tanks, and distribution units; RGM isolates were identified by using rpoB gene sequencing. We detected 18 RGM species and putative new species, with most isolates being Mycobacterium chelonae and Mycobacterium llatzerense. Using hierarchical clustering and principal-component analysis, we found that RGM were organized into various communities correlating with water origin (groundwater or surface water) and location within the distribution network. Water treatment plants were more specifically associated with species of the Mycobacterium septicum group. On average, M. chelonae dominated network sites fed by surface water, and M. llatzerense dominated those fed by groundwater. Overall, the M. chelonae prevalence index increased along the distribution network and was associated with a correlative decrease in the prevalence index of M. llatzerense, suggesting competitive or niche exclusion between these two dominant species. Our data describe the great diversity and complexity of RGM species living in the interconnected environments that constitute the water production and distribution system of a large city and highlight the prevalence index of the potentially pathogenic species M. chelonae in the distribution network.

Paradoxical reactions during treatment of tuberculosis with extrapulmonary manifestations in HIV-negative patients.

PURPOSE: Tuberculous paradoxical reactions (PR) have been seldom studied in non-immunocompromised patients. We conducted a study to describe the incidence, clinical and biological features, treatment and outcome of PR in human immunodeficiency virus (HIV)-negative patients treated for extrapulmonary tuberculosis (TB) and to identify predictive factors of PR. METHODS: A single-center retrospective study was conducted in consecutive HIV-negative patients presenting with TB with at least one extrapulmonary manifestation who were hospitalized in an internal medicine department between 2000 and 2010. RESULTS: Seventy-six patients were enrolled in the study. Lymphadenitis was the most common extrapulmonary manifestation of tuberculosis among this patient population (72 %). PR occurred in 19 (25 %) patients, mostly involving the lymph nodes (68 %) and lung (16 %), but also the pericardium, pleura, bone, muscle and brain. Median time to PR onset after initiation of anti-TB regimen was 86 days (interquartile range 36-125). Treatment of PR consisted mainly of corticosteroids (47 % of patients) and needle aspiration of PR lymph nodes (31 %). Peripheral lymph node involvement (p = 0.009), lymphopenia (p = 0.03) and anemia (p = 0.002) at presentation were associated with PR occurrence. Outcome was favorable in all patients with PR but one; the latter suffered residual paraplegia. CONCLUSIONS: Paradoxical reactions are frequent in the course of extrapulmonary TB treatment in HIV-negative patients but their outcome is excellent, except in some cases with central nervous system involvement.

[Drug resistance testing of Mycobacterium tuberculosis isolates from sputum in Chad]. / Étude de la résistance de Mycobacterium tuberculosis chez les patients bacillifères au Tchad.

Culture and resistance testing of Mycobacterium tuberculosis are not regularly performed in Chad. Sputa were obtained from three different categories of hospitals (district, regional and national) in Chad. All examined sputa were smear-positive and were investigated by culture and drug resistance testing for first-line antituberculosis drugs. From 232 sputa positive for acid-fast bacilli, 135 isolates of M. tuberculosis from different patients (46 women, 89 men, mean age 34 years) were analyzed. All the patients except one corresponded to new cases of tuberculosis. In total, 27 out of 135 isolates (20%) were resistant to at least one major antituberculosis drug. Resistance to isoniazid was the most frequent resistance observed, with 18 isolates (13%) presenting at least this resistance. Three isolates (2.2%) were resistant to isoniazid and rifampicin (multidrug resistance MDR) including one isolate being concomitantly resistant to streptomycin and ethambutol. The resistance rate differed in relation to the category of the hospital; the most important resistance rate was observed in regional hospitals (33%), while it was 16% and 14% in the national and district hospitals, respectively. HIV serology was performed in 81 patients, among whom 20 (25%) were positive. This is the first study that shows that drug resistance of M. tuberculosis is present in Chad. Besides single drug-resistant isolates, multidrug-resistant strains of M. tuberculosis could also be identified. This result highlights the urgency of initiating actions to detect drug resistance and limit the spread of drug-resistant strains.

[A prospective study of antibiotic prescribing in an emergency care unit]. / Evaluation de la qualité des prescriptions d'antibiotiques dans le service d'accueil des urgences d'un CHU en région parisienne.

OBJECTIVE: The aim of the study was to assess the quality of the initial prescription of antibiotics in an emergency care unit (ECU). DESIGN: A two-week prospective observational study was performed in the ECU Ambroise-Paré covering all patients that were given antibiotic prescriptions. The antibiotic treatments were reviewed by medical experts and confronted with the recommendations of the local guide to antibiotic protocols (referential). Treatments were considered appropriate if indication, choice of the molecule, and route of administration complied to protocols; unacceptable if the indication or the choice of antibiotic was incorrect; debatable in all other cases. RESULTS: One hundred and four patients were reviewed over the two-week period. Treatments were prescribed mainly for urinary infections (31 cases), pulmonary (26) or cutaneous (23). In 84.5% of cases, indication was present in the referential. Beta-lactams accounted for 60% of prescriptions, followed by fluoroquinolones (32.5%). By combining three criteria (indication, choice and route of administration), only 54% of prescriptions were considered appropriate, 31% were debatable, and 15% unacceptable. Analysis showed that the quality of antibiotherapy was significantly better if the prescriber was informed about the inquiry and if the indication was present in the guidelines. CONCLUSION: The antibiotherapy manual is an indispensable tool for prescribers in the ECU, but it is insufficient to guarantee the quality of antibiotic prescriptions. Training sessions must be set up for emergency doctors, and the intervention of an infectious diseases specialist, as well as discussions about repeated clinical audit results, should enable a better use of antibiotics in the emergency unit.

[Evaluation of amoxicillin-clavulanic acid prescriptions in a teaching hospital of Parisian suburb]. / Evaluation des prescriptions d'amoxicilline-acide clavulanique dans un CHU de la région parisienne.

OBJECTIVE: Prospective study of amoxicillin-clavulanic acid (amox-clav) prescriptions in the medical departments of a teaching hospital that prescribes this antibiotic very often. DESIGN: From April to May 2004, each patient treated by amox-clav was included. Data were collected (age, sex, past diseases, associated-diseases, reason for hospitalization, prior antibiotic therapy, date of amox-clav prescription, indication for amox-clav prescription, other associated antibiotics, nosocomial or community-acquired infection, site of infection, bacteriologic samples and bacterial identification, treatment duration and status of the physician). Data were analysed by a muldisciplinary group and compared with a referential used for antibiotic prescriptions in our hospital. RESULTS: One hundred and two medical files were analysed. Seventy-one percent of amox-clav prescriptions were in adequation with the referential. Combination of three criteria (indication of antibiotic therapy, choice of amox-clav and of an antibiotic combination) showed that 58 (57%) was acceptable, 29 (28%) was debatable and 15 (15%) was unacceptable. Unacceptable prescriptions were often made by a junior. The majority of inadequate antibiotic prescriptions referred to acute pulmonary infections. Antibiotic combinations were often inadequate and treatment duration was too long. The quality of the prescription was more accurate when made by a senior. CONCLUSION: An effort should be made in our teaching hospital to optimize antibiotic prescriptions.

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.

Molecular epidemiology of Mycobacterium abscessus complex isolates in Ireland.

BACKGROUND: The Mycobacterium abscessus complex are the rapidly growing mycobacteria (RGM) most commonly causing lung disease, especially in cystic fibrosis (CF) patients. Ireland has the world's highest CF incidence. The molecular epidemiology of M. abscessus complex in Ireland is unreported. METHODS: We performed rpoB gene sequencing and multi-locus sequence typing (MLST) on M. abscessus complex strains isolated from thirty-six patients in 2006-2012 (eighteen known CF patients). RESULTS: Twenty-eight strains (78%) were M. abscessus subsp. abscessus, eight M. abscessus subsp. massiliense, none were M. abscessus subsp. bolletii. Sequence type 1 (ST1) and ST26 (M. abscessus subsp. abscessus) were commonest. Seven M. abscessus subsp. abscessus STs (25%) were novel (two with novel alleles). Seven M. abscessus subsp. massiliense STs were previously reported (88%), including two ST23, the globally successful clone. In 2012, of 552 CF patients screened, eleven were infected with M. abscessus complex strains (2%). CONCLUSIONS: The most prevalent M. abscessus subsp. abscessus and M. abscessus subsp. massiliense strains in Ireland belong to widely-distributed STs, but there is evidence of high M. abscessus subsp. abscessus diversity.

Evidence for a small anion-selective channel in the cell wall of Mycobacterium bovis BCG besides a wide cation-selective pore.

Two channels were observed in extracts of whole Mycobacterium bovis BCG cells using organic solvents and detergents. The channels derived from organic solvent treatment had a single-channel conductance of about 4.0 nS in 1 M KCl in lipid bilayer membranes with properties similar to those of the channels discovered previously in Mycobacterium smegmatis and Mycobacterium chelonae. The channel was in its open configuration only at low transmembrane potentials. At higher voltages it switched to closed states that were almost impermeable for ions. Lipid bilayer experiments in the presence of detergent extracts of whole cells revealed another channel with a single-channel conductance of only 780 pS in 1 M KCl. Our results indicate that the mycolic acid layer of M. bovis BCG contains two channels, one is cation-selective and its permeability properties can be finely controlled by cell wall asymmetry or potentials. The other one is anion-selective, has a rather small single-channel conductance and is voltage-insensitive. The concentration of channel-forming proteins in the cell wall seems to be small, which is in agreement with the low cell wall permeability for hydrophilic solutes.

Role of OxyS of Mycobacterium tuberculosis in oxidative stress: overexpression confers increased sensitivity to organic hydroperoxides.

Mycobacterial genomics has uncovered a novel regulatory gene, oxyS, belonging to the LysR family. There is extensive similarity in the DNA-binding domain of OxyS with that of OxyR, the oxidative stress response protein of many bacteria. Since the oxyR gene of Mycobacterium tuberculosis has been multiply inactivated during evolution it was conceivable that some of its functions could be effected by OxyS. It is shown here that OxyS is produced at low levels and that there are at least three different oxyS alleles present in clinical isolates of M. tuberculosis that are susceptible or resistant to isoniazid. Overproduction or depletion of OxyS did not affect susceptibility to isoniazid but increasing the concentration of the regulator lowered levels of the alkyl hydroperoxide reductase, AhpC, and rendered the tubercle bacillus more susceptible to organic hydroperoxides.

Isolation and characterization of isoniazid-resistant mutants of Mycobacterium smegmatis and M. aurum.

INH-resistant mutants of Mycobacterium aurum and M. smegmatis were isolated and characterized in an attempt to provide fresh insight into the activity of isoniazid (INH), a key antibiotic in the treatment of tuberculosis. In both cases, high levels of resistance were accompanied by slower growth rate, by loss of peroxidase and reduced catalase activities, although mycolic acid production was unaffected. A gene homologous to the katG gene of M. tuberculosis, encoding peroxidase-catalase, was detected in wild-type and INH-resistant strains and it appears that INH resistance may stem from the loss of its product.

On the catalase-peroxidase gene, katG, of Mycobacterium leprae and the implications for treatment of leprosy with isoniazid.

The toxicity of the potent tuberculocidal agent, isoniazid, is mediated by the heme-containing enzyme, catalase-peroxidase, encoded by the katG gene. Although isoniazid has been used for the treatment of leprosy, it is shown here that the katG gene of Mycobacterium leprae is a pseudogene, which has probably been inactivated by multiple mutations. Inactive genes were detected by the polymerase chain reaction in several isolates of M. leprae, of different geographical origins, and attempts to complement an isoniazid-resistant strain of Mycobacterium smegmatis with the katG pseudogene were unsuccessful. Isoniazid is thus likely to be of no therapeutic benefit to leprosy patients.

Familial outbreak of disseminated multidrug-resistant tuberculosis and meningitis.

Rapidly progressive multidrug-resistant tuberculosis (MDR-TB) is well documented in human immunodeficiency virus (HIV) positive subjects, but it is not fully recognised in HIV-negative subjects in the familial environment. We report three cases of MDR-TB in three young HIV-negative subjects from the same family. All the patients showed signs of meningitis during the course of their disease, and in two cases a resistant strain of Mycobacterium tuberculosis was isolated in cerebrospinal fluid. Two of the three subjects died from neurological complications; the other was successful treated utilising both systemic and intrathecal therapy for tuberculous meningitis. By a retrospective analysis of DNA obtained from Lowenstein-Jensen cultures, the strains were confirmed as M. tuberculosis resistant to rifampicin and isoniazid, and were closely related in the two cases where specimens were available for analysis. The resistance was acquired in two patients initially infected with a susceptible strain; in the other patient, the resistance was present on the first sensitivity test for which results were available. This report demonstrates the high risk of fatality from MDR-TB for HIV-negative subjects in the absence of reliable early diagnostic and preventive tools. It also reinforces the concept that genetic susceptibility to M. tuberculosis may be an important factor in the clinical presentation and outcome of MDR-TB.

Multidrug resistance in Mycobacterium tuberculosis.

All but one of the four major mechanisms of resistance to antimicrobial agents-inactivation of the drug, altered cell wall permeability or drug efflux, drug titration due to target overproduction, and alteration of the target by mutation-appear to be employed by Mycobacterium tuberculosis in its resistance to components of short course chemotherapy regimens. To date no enzymes capable of inactivating any of the frontline drugs have been found. The most common resistance mechanism is alteration of the target leading to inadequate drug binding, or drug activation, as a result of mutations in chromosomal genes. This occurs in the case of the specific antituberculous drugs isoniazid, pyrazinamide and ethionamide as well as in resistance to the broad-spectrum antibiotics, rifampicin, streptomycin and the fluoroquinolones. Overproduction of the drug target also appears to lead to resistance to isoniazid and ethionamide whereas changes in permeability, or the activation of antibiotic-efflux systems, may contribute to the low-level resistance of the tubercle bacillus to streptomycin and fluoroquinolones.

[Re-infection with a different strain after prosthesis revision for bacterial infection: 13 cases]. / Réinfection avec changement de germe après réimplantation de prothèses pour infection: à propos de 13 cas.

PURPOSE OF THE STUDY: Treatment of an infected arthroplasty is always a delicate task. Multidisciplinary management involving surgeons, clinicians, bacteriologists, and the patient may be long and not always successful. Rare re-infections caused by a bacterial strain different from the initial strain may be a cause of failure. We analyzed cases of re-infection with a different strain in search of an explanation. MATERIAL AND METHODS: We reviewed 13 cases of re-infection in 12 patients with 7 hip and 5 knee arthroplasties. The causal germ had been clearly identified by the bacteriology laboratory during the first infection. The antibiotic regimens were confirmed by the medical team. All patients underwent surgery in our unit. At the time of the second infection, the implant had been removed, had been left in place, or had been changed. We recorded the new strains isolated and studied their antibiotic susceptibility profile. Treatment protocols and biological and functional results were analyzed. RESULTS: A mean 27 months after the re-infection, clinical and biological success had been achieved in 7 cases. The failures more frequently corresponded to cases where the first infection was caused by an aggressive germ and where the second germ was found during reimplantation. DISCUSSION: Theoretically a change in the causal germ could be explained by an insufficient initial biological analysis with an unrecognized or masked germ, by peroperative contamination subsequent to the difficulties observed in these hospitalized patients, and finally by secondary contamination. We recall the criteria of secondary infection (free interval, distant infectious focus, time sequence), measures taken to prevent peroperative infections, and conditions for optimal bacteriological sampling. If no resistance emerges after the first antibiotic treatment, there could nevertheless be a selection of conditions enabling growth of germs infrequently encountered. We stress that re-infection should not be considered necessarily as a failure of initial management but can, in certain cases, be considered as a de novo infection, and treated as such.

In vitro activity of cefoxitin and imipenem against Mycobacterium abscessus complex.

The in vitro activity of cefoxitin and imipenem was compared for 43 strains of the Mycobacterium abscessus complex, mostly isolated from cystic fibrosis patients. The MICs of imipenem were lower than those of cefoxitin, although the number of imipenem-resistant strains was higher according to the CLSI breakpoints. Strain comparisons indicated that the MICs of cefoxitin were significantly higher for Mycobacterium bolletii than for M. abscessus. The MICs of both ß-lactams were higher for the rough morphotype than for the smooth morphotype. The clinical impact of the in vitro difference between the activity of imipenem and that of cefoxitin remains to be determined.