Odile Bajolet

Pseudomonas aeruginosa May Accumulate Drug Resistance Mechanisms without Losing Its Ability To Cause Bloodstream Infections

ABSTRACT In this study, we systematically investigated the resistance mechanisms to β-lactams, aminoglycosides, and fluoroquinolones of 120 bacteremic strains of Pseudomonas aeruginosa. Pulsed-field gel electrophoresis genotyping showed that 97 of these strains were represented by a single isolate, 10 by 2 and 1 by 3 clonally related isolates, respectively. Seventy-five percent (90 out of 120) of the bacteremic P. aeruginosa strains displayed a significant resistance to one or more of the tested antimicrobials (up to 11 for 1 strain). These strains were found to harbor a great diversity of resistance mechanisms (up to 7 in 1 strain), leading to various levels of drug resistance. Interestingly, 11 and 36% of the isolates appeared to overproduce the MexAB-OprM and MexXY-OprM efflux systems, respectively. Altogether, our results show that P. aeruginosa may accumulate intrinsic (overproduction of cephalosporinase AmpC, increased drug efflux, fluoroquinolone target mutations, and deficient production of porin OprD) and exogenous (production of secondary β-lactamases and aminoglycoside-modifying enzymes) resistance mechanisms without losing its ability to generate severe bloodstream infections. Consequently, clinicians should be aware that multidrug-resistant P. aeruginosa may remain fully pathogenic.

National multidrug-resistant bacteria (MDRB) surveillance in France through the RAISIN network: a 9 year experience

BACKGROUND In the mid-1990s, the prevalence rate of multidrug-resistant bacteria (MDRB) in French hospitals was high and control of MDRB spread then became a major priority in the national infection control programme (ICP). METHODS To evaluate the impact of the ICP, a national coordination of MDRB surveillance was set up in 2002. Data were collected 3 months a year in healthcare facilities (HCFs) on a voluntary basis. All clinical specimens of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLE) were prospectively included. Incidences per 1000 patient days (PDs) were calculated and trends in incidence from 2003 to 2010 were assessed. RESULTS Participation in the surveillance increased from 478 HCFs in 2002 to 933 in 2010. In 2010, MRSA incidence was 0.40/1000 PDs: 1.14 in intensive care units (ICUs), 0.48 in acute care facilities (ACFs) and 0.27 in rehabilitation and long-term care facilities (RLTCFs). ESBLE incidence was 0.39/1000 PDs: 1.63 in ICUs, 0.46 in ACFs and 0.23 in RLTCFs. MRSA incidence significantly decreased from 0.72/1000 PDs in 2003 to 0.41/1000 PDs in 2010 (P<10(-3)); in contrast, ESBLE incidence significantly increased from 0.17/1000 PDs to 0.48/1000 PDs (P<10(-3)). The most prevalent ESBLE were Enterobacter aerogenes (34%) and Escherichia coli (25%) in 2003 and E. coli (60%) and Klebsiella pneumoniae (18%) in 2010. CONCLUSION These results demonstrate the positive impact of the national ICP on MRSA rates. In contrast, ESBLE incidence, especially ESBL-producing E. coli, is increasing dramatically and represents a serious threat for hospitals and for the community that deserves specific control actions.

Gastroscopy-associated transmission of extended-spectrum beta-lactamase-producing Pseudomonas aeruginosa

An unusual multi-drug-resistant Pseudomonas aeruginosa (MDR-PA) was isolated in four patients whilst hospitalized in a French teaching hospital between May and August 2011. All four patients had undergone an oesophago-gastro-duodenoscopy with the same gastroscope over a five-month period. This endoscope was associated with a culture positive for the MDR-PA. Observations of endoscope reprocessing identified deviations from the agreed processes: insufficient initial cleaning, shortening of the immersion time and brushing time, insufficient channel flushing, and inadequate drying prior to storage. Since withdrawing the gastroscope and institution of strict adherence to the agreed processes, no other MDR-PA cases have been isolated.

Description of a 2,683-base-pair plasmid containing qnrD in two Providencia rettgeri isolates.

ABSTRACT qnr genes are plasmid-mediated quinolone resistance genes mainly harbored on large conjugative multiresistant plasmids. The qnrD gene was recently observed in Salmonella enterica on a small nonconjugative plasmid (p2007057). We describe two strains of Providencia rettgeri harboring qnrD on nonconjugative plasmids. The plasmids were 99% identical, with 2,683 bp and four open reading frames, including qnrD, but exhibited only 53% identity with the plasmid found in S. enterica.

Fluoroquinolone Resistance Mechanisms and population structure of Enterobacter cloacae non-susceptible to Ertapenem in North-Eastern France.

Fluoroquinolone (FQ) agents are a potential resort to treat infection due to Enterobacteriaceae producing extended spectrum β-lactamase and susceptible to FQ. In a context of increase of non-susceptibility to carbapenems among Enterobacteriaceae, we characterized FQ resistance mechanisms in 75 Enterobacter cloacae isolates non-susceptible to ertapenem in North-Eastern France in 2012 and describe the population structure by pulsed field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Among them, 14.7% (12/75) carried a carbapenemase-encoding gene. Except one isolate producing VIM-1, the carbapenemase-producing isolates carried the well-known IncL/M pOXA48a plasmid. Most of the isolates (59/75) harbored at least a FQ-R determinant. qnr genes were predominant (40%, 30/75). The MLST study revealed that E. cloacae isolates’ clonality was wide [24 different sequence types (STs)]. The more widespread STs were ST74, ST101, ST110, ST114, and ST133. Carbapenem MICs were higher for E. cloacae ST74 than for other E. cloacae isolates. Plasmid-mediated quinolone resistance determinants were more often observed in E. cloacae ST74 isolates. These findings showed that (i) pOXA-48a is spreading in North-Eastern France, (ii) qnr is preponderant in E. cloacae, (iii) E. cloacae comprised a large amount of lineages spreading in North-Eastern France, and (iv) FQ as an alternative to β-lactams to treat ertapenem non-susceptible Enterobacteriaceae are compromised.

Postoperative spondylodiskitis due to Stomatococcus mucilaginosus in an immunocompetent patient.

A case is reported of postoperative spondylodiskitis due to Stomatococcus mucilaginosus in an immunocompetent woman. The route of infection remains unknown. Intravenous treatment with cefotaxime and fosfomycin was given, followed by oral administration of rifampin and pristinamycin until resolution of infection. This report shows that this bacterium can cause severe infections in immunocompetent patients.

Poor knowledge among French travellers of the risk of acquiring multidrug-resistant bacteria during travel

Since it is not routine practice in France to raise public awareness about the risk of acquiring multidrug-resistant Enterobacteriaceae (MRE) during international travel, we aimed to determine, among French travellers attending a consultation for travel medicine, their level of knowledge about the risk of acquiring MRE. Among 191 adults enrolled in the study, only 10% of travellers were aware of the risk of becoming a carrier of MRE during travel, and 87% did not understand the difference between being colonized with MRE, and having a clinical infection with MRE. Consultations for travel medicine could be an opportunity to deliver specific information about the risks of acquiring MRE. Antibiotic resistance among Gram-negative bacteria is an emerging problem worldwide, mainly with the diffusion of extended spectrum beta-lactamase, plasmid-encoded cephalosporinases and carbapenemases-producing Enterobacteriaceae. These strains often show multi-resistance and are now diffusing worldwide in the community setting, outside of the hospital. Travel in areas endemic for multidrug-resistant Enterobacteriaceae (MRE) has been identified as a risk factor for the acquisition of MRE.1–5 Faecal colonization with MRE is very frequent among travellers to tropical regions, with a risk ranging from 20 to 70%, especially among those visiting the South Asian continent.2,3,5 Moreover, antibiotic use could favour proliferation of MRE by disrupting the intestinal microbiota balance, and the use of antibiotics for travel diarrhoea was associated with a 4-fold increase in the risk of acquiring MRE, whereas travel diarrhoea itself was only associated with a 2-fold increase in risk.2,3,6 Taken together, these elements suggest that informing the public about the risk of acquiring MRE during international travel could represent a preventive measure against the spread of MRE in France. The French public has been made aware of multidrug-resistant (MDR) bacteria through a media campaign conducted …

Mise au point d’une technique de PCR en temps réel pour la détection rapide des gènes qnr chez des entérobactéries productrices de bêta-lactamases à spectre étendu

AIM OF THE STUDY To develop a fast and reliable real time PCR technique for detecting plasmid-mediated quinolone resistance genes qnrA, qnrB and qnrS. METHODS A real-time PCR assay using SYBR Green I and Roche LightCycler(®) was developed to detect qnr genes. Detection of qnr genes was based on comparison of melting temperature differences with a positive control of each qnr genes. This assay was performed to study 138 isolates collected from diagnostic and screening samples in the Champagne-Ardenne region in 2004 (France). RESULTS In optimized conditions, the three positive controls tested alone and with isolates confirmed the specificity of the PCR primers. Each PCR assay was able to test 30 strains in 60min for 1 qnr gene. Out of 138 isolates screened, 3.6 % isolates were positive for a qnrA1, 1.5 % for qnrS1 and no qnrB-like gene. Prevalence of qnr determinants was 5 % and reached 9.5 % in clinical isolates. CONCLUSION Real-time PCR is a fast and reliable technique for screening of qnr-positive strains. This study shows a relatively high prevalence of qnr determinants (5 %) among ESBL-producing Enterobacteriaceae.

Infections in Total Hip and Total Knee Arthroplasty: Development of a Score To Assess Endogenous Risk of Surgical Site Infections

BACKGROUND Surgical site infections (SSI) are a dreaded complication of total hip (THA) and knee arthroplasties (TKA), and are a major public health concern. Risk factors are well known, but no endogenous risk assessment score exists. The objective of this study to develop a score to assess endogenous risk of infection after THA or TKA. METHODS All infections after TKA and THA implanted in the department of orthopedic surgery of a teaching hospital between January 2007 and December 2012 were included. Two control groups were matched to cases on the type of prosthesis (hip or knee; first-line or revision). RESULTS Twenty-four SSIs after THA and 21 after TKA were registered (respective incidence during the study period: 1.56 and 1.91%). Relevant endogenous risk factors found were: Smoking (adjusted odds ratio=3.9), a BMI greater than 35 kg/mÇ (1.8), inflammatory rheumatism (7.3), and the number of operations (prosthetic or not) on the involved joint (2.9 per additional surgery). The average score of endogenous infection risk on all analyzed subjects was 3.37±3.33 (median=3, range=0-17). Mean scores were substantially different among cases and control groups: Respectively 5.84±4.04 vs 2.13±2.01 (p<0.0001). With a five-point threshold, the sensitivity and specificity of the score are respectively 62 and 91%. ASA score greater than or equal to three was not found to be substantial risk factor in this study (p=0.15). CONCLUSIONS Endogenous infection risk score studied here was found to be relevant in discriminating cases from control groups, but requires validation in a larger cohort.

Factors associated with carriage of carbapenem-non-susceptible Enterobacteriaceaein North-Eastern France and outcomes of infected patients

Background Carbapenems are frequently used as a last resort to treat infections caused by multidrug-resistant Gram-negative organisms, thus carbapenem-non-susceptible Enterobacteriaceae (CNSE) is an emerging health threat. Objectives To assess risk factors and outcomes of CNSE carriage. Patients and methods We conducted a matched case-control study in six hospitals in North-Eastern France. The controls were patients harbouring carbapenem-susceptible Enterobacteriaceae. Fifty-five cases and 110 controls were included. Results Most of the CNSE isolates were Enterobacter cloacae and Klebsiella pneumoniae . Carbapenemase production was observed in 40% of isolates and they produced OXA-48 only. CNSE carriage was significantly associated with recent antibiotic use ( P =  0.014), particularly carbapenems ( P =  0.03) and fluoroquinolones ( P =  0.016). A multivariate analysis using conditional logistic regression showed that the presence of concomitant infection(s) (OR: 9.83; 95% CI 3.04-21.39, P =  0.0031), nosocomial infections (OR: 7.84; 95% CI 2.00-12.54, P  =   0.0063) and a high age (OR: 1.07; 95% CI 1.01-1.06, P =  0.038) were independently associated with CNSE carriage. Moreover, patients infected with CNSE had worse outcomes: fewer resolved infections at 1 month ( P =  0.02), and they had a higher mortality rate ( P =  0.0004) and longer hospital stays ( P =  0.02). Conclusions We identified three independent risk factors for CNSE carriage as well as worse outcomes in infected patients in North-Eastern France. This highlights the importance of early detection of CNSE and the need for antimicrobial therapy re-evaluation after bacteriological analysis has been performed.