Patrick Legrand

TRANSFERABLE ENZYMATIC RESISTANCE TO THIRD-GENERATION CEPHALOSPORINS DURING NOSOCOMIAL OUTBREAK OF MULTIRESISTANT KLEBSIELLA PNEUMONIAE

Klebsiella pneumoniae strains that were resistant to third-generation cephalosporins and amikacin were recovered from 62 of 395 patients (15.7%) during 1986. 25 isolates (40%) caused urinary tract infections. The outbreak involved three intensive care units (54 isolates), and spread from one unit to another and then to four wards (8 isolates). K pneumoniae of various serotypes and strains of different Enterobacteriaceae demonstrating the same antibiotic resistance pattern were isolated, which suggests dissemination of an R-factor. The isolates had low-level resistance to third-generation cephalosporins (mode minimum inhibitory concentration of cefotaxime, 2 mg/l) but remained sensitive to cephamycins. Cefotaxime was effective in cases of uncomplicated urinary tract infection, but failed in major infections at other sites. 1-5 mg/l of the beta-lactamase inhibitors clavulanic acid or sulbactam restored normal activity to cefotaxime against the multiresistant strains. Resistance to third-generation cephalosporins was mediated by a new broad-spectrum enzyme of isoelectric point 6.3. Resistance to beta-lactams and aminoglycosides was transferable to Escherichia coli. The emergence of transferable enzymatic resistance to newer beta-lactams in K pneumoniae strains indicates a major risk of spread of such resistance to otherwise sensitive strains.

Intestinal Decontamination for Control of Nosocomial Multiresistant Gram-Negative Bacilli: Study of an Outbreak in an Intensive Care Unit

STUDY OBJECTIVE To study the efficacy of intestinal decontamination by oral nonabsorbable antibiotic agents to control a nosocomial outbreak of intestinal colonization and infection with multiresistant Enterobacteriaceae, and to examine its effects on endemic nosocomial infection rates. DESIGN A 10-week prospective incidence study (group 1), and then an 8-week randomized, open trial of intestinal decontamination (groups 2 and 3). SETTING A medical intensive care unit of a tertiary care university hospital. PATIENTS Consecutive patients with unit stay of over 2 days and a severity score at admission of more than 2; 124 patients were included in group 1, 50 in group 2 (control), and 36 in group 3 (intestinal decontamination). INTERVENTIONS Neomycin, polymyxin E, and nalidixic acid were given to group 3 patients throughout their stay in the unit. MEASUREMENTS AND MAIN RESULTS Intestinal colonization with multiresistant strains occurred in 19.6% of patients in group 1, at a mean of 16 days after admission, and preceded detection in clinical samples by a mean of 11 days. During the decontamination trial, intestinal colonization rates decreased to 10% (group 2), and 3% (group 3) (P = 0.12 and P less than 0.01, compared with group 1, respectively). Corresponding infection rates were 9% (group 1), 3% (group 2), and 0 (group 3). No new cases were detected in the following 4 months. The intestinal colonization rate with gram-positive cocci was higher in group 3 than group 2 (P less than 0.001). The overall rate of nosocomial infections was at 28% (group 1), 33% (group 2), and 32% (group 3). CONCLUSIONS Intestinal decontamination can help to control an outbreak of intestinal colonization and infection with multiresistant gram-negative bacilli in the intensive care unit, but should not be recommended for routine prevention of endemic nosocomial infections.

Efficacy of handrubbing with alcohol based solution versus standard handwashing with antiseptic soap: randomised clinical trial

Abstract Objective: To compare the efficacy of handrubbing with an alcohol based solution versus conventional handwashing with antiseptic soap in reducing hand contamination during routine patient care. Design: Randomised controlled trial during daily nursing sessions of 2 to 3 hours Setting: Three intensive care units in a French university hospital Participants: 23 healthcare workers Interventions: Handrubbing with alcohol based solution (n=12) or handwashing with antiseptic soap (n=11) when hand hygiene was indicated before and after patient care. Imprints taken of fingertips and palm of dominant hand before and after hand hygiene procedure. Bacterial counts quantified blindly Main outcome measures: Bacterial reduction of hand contamination. Results: With handrubbing the median percentage reduction in bacterial contamination was significantly higher than with handwashing (83% v 58%, P=0.012), with a median difference in the percentage reduction of 26% (95% confidence interval 8% to 44%). The medianduration of hand hygiene was 30 seconds in each group. Conclusions: During routine patient care handrubbing with an alcohol based solution is significantly more efficient in reducing hand contamination than handwashing with antiseptic soap.

Selective Screening of Carriers for Control of Methicillin-Resistant Staphylococcus aureus (MRSA) in High-Risk Hospital Areas with a High Level of Endemic MRSA

Screening for methicillin-resistant Staphylococcus aureus (MRSA) carriage in patients at risk was evaluated as part of a control program in a 26-bed medical intensive care unit (ICU) of a university hospital with a high level of endemic MRSA. Control measures included isolation and barrier precautions, skin decolonization with chlorhexidine of patients from whom MRSA was recovered, and mupirocin treatment of nasal carriers of MRSA. Of 3,686 patients admitted during a 4-year period, 44% were screened, which occurred during admission for 38%; MRSA was recovered from 293 patients (8%). There were 150 imported cases and 143 ICU-acquired cases, of which 51% and 45%, respectively, were first identified through screening. Nasal swab cultures identified 84% of MRSA carriers. The incidence of all ICU-acquired cases and of acquired colonization or infection decreased from 5.8% and 5.6% to 2.6% and 1.4% (P = .002 and P < .001), respectively, whereas that of imported cases remained unchanged (range, 3.8% to 4.3%; P = .8). Selective screening for nasal carriage during admission to high-risk areas may contribute to identification of a substantial proportion of cases of MRSA and to early implementation of effective control measures.

Curbing methicillin-resistant Staphylococcus aureus in 38 French hospitals through a 15-year institutional control program.

BACKGROUND The Assistance Publique-Hôpitaux de Paris (AP-HP) institution administers 38 teaching hospitals (23 acute care and 15 rehabilitation and long-term care hospitals; total, 23 000 beds) scattered across Paris and surrounding suburbs in France. In the late 1980s, the proportion of methicillin resistance among clinical strains of Staphylococcus aureus (MRSA) reached approximately 40% at AP-HP. METHODS A program aimed at curbing the MRSA burden was launched in 1993, based on passive and active surveillance, barrier precautions, training, and feedback. This program, supported by the strong commitment of the institution, was reinforced in 2001 by a campaign promoting the use of alcohol-based hand-rub solutions. An observational study on MRSA rate was prospectively carried out from 1993 onwards. RESULTS There was a significant progressive decrease in MRSA burden (-35%) from 1993 to 2007, whether recorded as the proportion (expressed as percentage) of MRSA among S aureus strains (41.0% down to 26.6% overall; 45.3% to 24.2% in blood cultures) or incidence of MRSA cases (0.86 down to 0.56 per 1000 hospital days). The MRSA burden decreased more markedly in intensive care units (-59%) than in surgical (-44%) and medical (-32%) wards. The use of ABHR solutions (in liters per 1000 hospital days) increased steadily from 2 L to 21 L (to 26 L in acute care hospitals and to 10 L in rehabilitation and long-term care hospitals) following the campaign. CONCLUSION A sustained reduction of MRSA burden can be obtained at the scale of a large hospital institution with high endemic MRSA rates, providing that an intensive program is maintained for a long period.

Campylobacter Bacteremia: Clinical Features and Factors Associated with Fatal Outcome

BACKGROUND Campylobacter bacteremia is uncommon. The influence of underlying conditions and of the impact of antibiotics on infection outcome are not known. METHODS From January 2000 through December 2004, 183 episodes of Campylobacter bacteremia were identified in 23 hospitals in the Paris, France, area. The medical records were reviewed. Characteristics of bacteremia due to Campylobacter fetus and to other Campylobacter species were compared. Logistic regression analysis was performed to identify risk factors for fatal outcome within 30 days. RESULTS Most affected patients were elderly or immunocompromised. C. fetus was the most commonly identified species (in 53% of patients). The main underlying conditions were liver disease (39%) and cancer (38%). The main clinical manifestations were diarrhea (33%) and skin infection (16%). Twenty-seven patients (15%) died within 30 days. Compared with patients with bacteremia due to other Campylobacter species, patients with C. fetus bacteremia were older (mean age, 69.5 years vs. 55.6 years; P = .001) and were more likely to have cellulitis (19% vs. 7%; P = .03), endovascular infection (13% vs. 1%; P = .007), or infection associated with a medical device (7% vs. 0%; P = .02). Independent risk factors for death were cancer (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.2-20.8) and asymptomatic infection (OR, 6.7; 95% CI, 1.5-29.4) for C. fetus bacteremia, the absence of prescription of appropriate antibiotics (OR, 12.2; 95% CI, 0.9-157.5), and prescription of third-generation cephalosporins (OR, 10.2; 95% CI, 1.9-53.7) for bacteremia caused by other species. CONCLUSIONS Campylobacter bacteremia occurs mainly in immunocompromised patients. Clinical features and risk factors of death differ by infection species.

Reemergence of Gentamicin-Susceptible Strains of Methicillin-Resistant Staphylococcus aureus: Roles of an Infection Control Program and Changes in Aminoglycoside Use

The spread of methicillin-resistant Staphylococcus aureus (MRSA) in our hospital in the 1980s correlated with increasing acquisition of resistance to antibiotics including gentamicin, rifampin, and fluoroquinolones. During the period 1993-1995, there was a major change in clinical MRSA isolates: the percentage of aminoglycoside-resistant MRSA isolates decreased from 75% to 52%, while the proportion of heterogeneous MRSA strains susceptible to gentamicin, rifampin, and tetracycline increased gradually from 4.9% to 27.5%. We used five epidemiological markers (i.e., antibiotyping, phage typing, pulsed-field gel electrophoresis, and restriction analysis of PCR amplified coagulase and protein A genes) to characterize recent isolates. With use of these techniques, we confirmed the persistence of the aminoglycoside-resistant MRSA clone and identified a clone of erythromycin-susceptible strains among the gentamicin-susceptible isolates and found that the remaining strains were diverse. These changes were due to the introduction of various MRSA strains from outside the hospital, while implementation of infection control measures in 1991 could have led to reduced transmission of the aminoglycoside-resistant MRSA strain. Changes in antibiotic prescribing patterns that resulted in reduced selective pressure from gentamicin may have contributed to the spread of gentamicin-susceptible MRSA strains.

In vitro susceptibility of Actinobaculum schaalii to 12 antimicrobial agents and molecular analysis of fluoroquinolone resistance

OBJECTIVES To assess the in vitro susceptibility of Actinobaculum schaalii to 12 antimicrobial agents as well as to dissect the genetic basis of fluoroquinolone resistance. METHODS Forty-eight human clinical isolates of A. schaalii collected in Switzerland and France were studied. Each isolate was identified by 16S rRNA sequencing. MICs of amoxicillin, ceftriaxone, gentamicin, vancomycin, clindamycin, linezolid, ciprofloxacin, levofloxacin, moxifloxacin, co-trimoxazole, nitrofurantoin and metronidazole were determined using the Etest method. Interpretation of results was made according to EUCAST clinical breakpoints. The quinolone-resistance-determining regions (QRDRs) of gyrA and parC genes were also identified and sequence analysis was performed for all 48 strains. RESULTS All isolates were susceptible to amoxicillin, ceftriaxone, gentamicin, clindamycin (except three), vancomycin, linezolid and nitrofurantoin, whereas 100% and 85% were resistant to ciprofloxacin/metronidazole and co-trimoxazole, respectively. Greater than or equal to 90% of isolates were susceptible to the other tested fluoroquinolones, and only one strain was highly resistant to levofloxacin (MIC ≥32 mg/L) and moxifloxacin (MIC 8 mg/L). All isolates that were susceptible or low-level resistant to levofloxacin/moxifloxacin (n = 47) showed identical GyrA and ParC amino acid QRDR sequences. In contrast, the isolate exhibiting high-level resistance to levofloxacin and moxifloxacin possessed a unique mutation in GyrA, Ala83Val (Escherichia coli numbering), whereas no mutation was present in ParC. CONCLUSIONS When an infection caused by A. schaalii is suspected, there is a risk of clinical failure by treating with ciprofloxacin or co-trimoxazole, and β-lactams should be preferred. In addition, acquired resistance to fluoroquinolones more active against Gram-positive bacteria is possible.

Bacteremia in Stevens-Johnson syndrome and toxic epidermal necrolysis: epidemiology, risk factors, and predictive value of skin cultures.

Toxic epidermal necrolysis (TEN) is a rare drug-related life-threatening acute condition. Sepsis is the main cause of mortality. Skin colonization on top of impaired barrier function promotes bloodstream infections (BSI). We conducted this study to describe the epidemiology, identify early predictors of BSI, and assess the predictive value for bacteremia of routine skin surface cultures. We retrospectively analyzed the charts of all patients with Stevens-Johnson syndrome (SJS) and TEN hospitalized over an 11-year period. Blood cultures and skin isolates were recovered from the microbiology laboratory database. Early predictors of BSI were identified using a Cox model. Sensitivity, specificity, and negative and positive predictive values of skin cultures for the etiology of BSI were assessed. The study included 179 patients, classified as having SJS (n = 54; 30.2%), SJS/TEN overlap (n = 59; 33.0%), and TEN (n = 66; 36.9%). Forty-eight episodes of BSI occurred, yielding a rate of 15.5/1000 patient days. Inhospital mortality was 13.4% (24/179). Overall, 70 pathogens were recovered, mainly Staphylococcus aureus (n = 23/70; 32.8%), Pseudomonas aeruginosa (n = 15/70; 21.4%), and Enterobacteriaceae organisms (n = 17/70; 24.3%). Variables associated with BSI in multivariate analysis included age >40 years (hazard ratio [HR], 2.5; 95% confidence interval [CI], 1.35-4.63), white blood cell count >10,000/mm3 (HR, 1.9; 95% CI, 0.96-3.61), and percentage of detached body surface area ≥30% (HR, 2.5; 95% CI, 1.13-5.47). Skin cultures had an excellent negative predictive value for bacteremia due to S aureus (especially methicillin-resistant strains) and P aeruginosa, but not for those due to Enterobacteriaceae organisms. In contrast, the positive predictive value was low for all pathogens studied. To our knowledge, this is the largest study describing the epidemiology and risk factors of BSI in patients with SJS/TEN. The body surface area involved is the main predictor of BSI. Excellent negative predictive values of skin cultures for S aureus and P aeruginosa bacteremia should help clinicians consider targeted empirical antibiotic choices when appropriate. Abbreviations: BSI = bloodstream infection, CI = confidence interval, HR = hazard ratio, ICU = intensive care unit, IQR = interquartile range, IVIG = intravenous immunoglobulin, LOD score = Logistic Organ Dysfunction score, NPV = negative predictive value, OR = odds ratio, SAPS II = Simplified Acute Physiology Score II, SJS = Stevens-Johnson syndrome, TEN = toxic epidermal necrolysis.

Aerococcus urinae and Aerococcus sanguinicola, two frequently misidentified uropathogens

Abstract Species belonging to the Aerococcus genus are isolated from the urine and blood of elderly patients suffering from urinary tract infections (UTIs). However, the clinical significance, phenotypic features and antimicrobial susceptibilities of these underestimated and/or misidentified species remain unclear. From March 2006 to November 2008, among 350 non-enterococcal Streptococcaceae species isolated from urinary specimens, 30 (8.6%) Aerococcus spp. strains were recovered. All strains were characterized using a phenotypic approach (API 20 STREP, ID 32 STREP and VITEK 2 systems), 16S rRNA gene sequencing, and susceptibility to antimicrobial agents commonly used in UTIs. The average age of patients was 73 y and most of them presented with a predisposing urological disease (31%) and/or a systemic underlying condition (48%). All isolates were identified to the species level using the molecular tool (Aerococcus urinae, n = 20; Aerococcus sanguinicola, n = 8; Aerococcus viridans, n = 2), whereas the phenotypic methods were frequently unreliable. All aerococcal isolates were susceptible to amoxicillin, vancomycin, and teicoplanin and showed a low-level resistance to gentamicin. Fluoroquinolones, co-trimoxazole, and fosfomycin exhibited a variable activity. Most A. urinae isolates were resistant to co-trimoxazole and susceptible to fosfomycin, whereas all A. sanguinicola isolates were resistant to fosfomycin and susceptible to co-trimoxazole.