Influence of fluoroquinolone consumption in inpatients and outpatients on ciprofloxacin-resistant Escherichia coli in a university hospital.

BACKGROUND: The increase in fluoroquinolone-resistant Escherichia coli has raised the issue of treatment failure in common infections. Few studies have investigated the possible relationship between outpatient fluoroquinolone consumption and resistance in hospital. OBJECTIVE: To investigate the relationship between inpatient and outpatient fluoroquinolone use and ciprofloxacin-resistant E. coli in a teaching hospital. METHODS: An ecological study was conducted in Toulouse University Hospital and its surrounding area, the Midi-Pyrénées region (south-western France), in 2004-07. Dynamic regression models were built to study how the hospital resistance rate was linearly related to current and past values of fluoroquinolone consumption. Resistance forecasts for 2008 were then calculated and compared with actual rates for the first 5 months of the year. RESULTS: Mean resistance rate was 13.7% and mean fluoroquinolone use was 89.9 defined daily doses (DDDs)/1000 inpatient days in hospital and 2.6 DDDs/1000 inhabitants/day in the region. Taking into account past values of fluoroquinolone consumption in hospital and in outpatients, only levofloxacin use in the community remained significantly associated with resistance in hospital, with a lag of 12 months. This model explained 50% of the resistance variability. CONCLUSIONS: This ecological analysis, conducted on a teaching hospital scale, suggests that ciprofloxacin resistance in E. coli in hospital is linked to consumption of fluoroquinolones within the hospital and its surrounding community. Among all fluoroquinolones, levofloxacin use was found to be the most important factor. Consumption in outpatients appears to be a relevant determinant to consider in designing interventions to reduce resistance in hospitals.

Bacillus cereus infections in Traumatology-Orthopaedics Department: retrospective investigation and improvement of healthcare practices.

OBJECTIVE: To investigate 41 open fractures infected with Bacillus cereus in a Traumatology-Orthopaedy ward and propose a care protocol at admission. METHODS: All B. cereus strains isolated from patients hospitalized in the Traumatology-Orthopaedy ward between March 1997 and August 2001 were submitted to molecular analysis (RAPD and PFGE) in order to investigate a putative outbreak. Susceptibility to the main antibiotics and antiseptics used in this kind of surgery was also evaluated. RESULTS: The B. cereus clinical isolates were mainly isolated from patients who had initially open fractures and were not clonally related. Furthermore, analysis of the clinical data was in favour of a telluric contamination of the wound (wound contamination with terrestrial environments) before admission. Finally, betalactam antibiotics used for prophylactic chemotherapy were not effective against the strains tested as well as the antiseptics who displayed poor effect. CONCLUSION: B. cereus could be termed an emerging pathogen and people need to be aware of its potential importance in orthopaedic trauma cases. In this purpose, a systematic screening for B. cereus at admission should be necessary in front of patients with open fractures associated with telluric contamination. Furthermore, if this bacterium can be isolated, chemotherapy should be based upon ciprofloxacin that would prevent the development of B. cereus infection responsible for deleterious complications.

Cefepime in critically ill patients: continuous infusion vs. an intermittent dosing regimen.

The aim of this study was to compare the pharmacokinetic and pharmacodynamic parameters of a continuous infusion of cefepime vs. an intermittent regimen in critically ill adult patients with Gram-negative bacilli infection. The prospective randomized parallel study was carried out in 50 patients with severe pneumonia (n = 41) or bacteremia (n = 9). They received cefepime 4 g/d either as a continuous infusion or intermittent administration 2 x 2 g in combination with amikacin. Patient characteristics and the minimal inhibitory concentration (MIC) of the isolated bacteria were comparable. Clinical outcomes were assessed along with pharmacodynamic indices and compared in both groups (chi2 and Mann-Whitney U-tests). Mechanical ventilation, clinical outcome and bacteriological eradication did not significantly differ between the two groups. Also, the area under the plasma cefepime concentration curve at steady state (AUCss: 612 +/- 369 vs. 623 +/- 319 mg x 1(-1) x h), AUCss > MIC (595 +/- 364 vs. 606 +/- 316 mg x 1(-1) x h) and the area under the inhibitory concentration curve (AUICss: 4258 +/- 5819 vs. 5194 +/- 7465 mg x 1(-1) x h) were similar. If the time above MIC (t > MIC) was not significantly higher in Group 1 (100 +/- 0%) than in Group 2 (90 +/- 11%), t > five-fold MIC in Group 1 (100 +/- 0%) was significantly higher (p < 0.01) than in Group 2 (82 +/- 25%). The mean time over the French breakpoint (4 mg/l) was 100 +/- 0% and 72 +/- 27% in Group 1 and 2 (p < 0.001), respectively. In contrast to intermittent cefepime administration, continuous infusion of cefepime consistently maintained a serum concentration > 5 x the MIC of typical Gram-negative nosocomial pathogens. This results in greater bactericidal activity against organisms with a higher (2 mg/l) cefepime breakpoint even if the clinical outcome is not significantly modified.

[Bartonella endocarditis on native valves. Apropos of 2 cases]. / Endocardite a Bartonella sur valve native. A propos de 2 cas.

The authors report two cases of Bartonella endocarditis in native valves. The first case was a 15 year old North African Girl who lived in poor social conditions and was admitted to hospital with pyrexia and congestive heart failure. Investigations revealed massive mitral regurgitation due to ruptured chordae tendinae, vegetations on the pulmonary valve with severe pulmonary hypertension due to persistent ductus arteriosus. After antibiotic therapy, the patient underwent surgery for mitral valve replacement, pulmonary valvuloplasty and closure of the patent ductus arteriosus. The second case was a 39 year old man with no fixed abode with a history of alcoholism who presented with a recurrent ischaemic stroke in a context of infection with a murmur of aortic regurgitation. Echocardiography showed a vegetation on the aortic valve with grade III/IV regurgitation requiring aortic valve replacement with a homograft after antibiotic therapy. The aetiological diagnosis was made a posteriori by the finding of high antibody titres and specific genetic amplification of Bartonella. In patients with negative blood cultures, Bartonella infection should be looked for systematically especially in those living under poor social conditions. The practical diagnostic investigation of endocarditis with negative blood cultures is reviewed.

[Multiple mononeuritis and cerebral meningo-arteritis. Wegener disease or Lyme disease?]. / Mononévrite multiple et méningo-artérite cérébrale. Maladie de Wegener ou maladie de Lyme?

The pathogenic mechanisms underlying Lyme disease remain uncertain but an increasing number of reports suggest a vascular inflammatory process. On the other hand, the so-called systemic vasculitides, even though they remain of pathological definition, have recently been characterized by the presence, in the serum, of anti-neutrophil cytoplasmic antibodies (ANCA). We report on a patient, finally diagnosed as having neuroborreliosis, who presented initially with multiple mononeuropathy, ANCA, vascular lesions at muscle biopsy and lymphocytic meningitis. Despite antibiotherapy, he presented with two recurrent strokes, from which he completely recovered. He also developed oto-sinusitis. The disease was finally clinically and biologically controlled by immunosuppressive therapy. The relationship between angiitis and Lyme disease are discussed. It is hypothesized that Borrelia burgdorferi infection may cause a systemic vasculitis following its own course and requiring its own treatment.

[Severe methicillin-resistant Staphylococcus aureus infections. Emergence of resistance to fusidic acid or fosfomycin during treatment with continuous infusion of vancomycin]. / Infections sévères à Staphylococcus aureus mticillino-résistants. Emergence de résistance à l'acide fusidique ou à la fostomycine lors du traitement par vancomycine en perfusion continue.

OBJECTIVES: To evaluate the development of resistance to fosfomycin or fucidic acid in severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and to assess the relationship with serum levels of vancomycin METHODS: A retrospective study was performed in patients hospitalized in our intensive care unit during a 3-year period (1993-1995) who were treated for severe MRSA infection with continuous infusion vacomycin and fosfomycin or fucidic acid. We analyzed the development of resistance and serum levels of vancomycin. RESULTS: During this period, only 20 patients received continuous infusion vancomycin plus fucidic acid or fosfomycin. MSRA resistant to fucidic or fosfomycin developed in 9. Vancomycin serum levels were significantly lower in patients who developed resistance to focidic acid or fosfomycin, both during the first 5 days of treatment (16.68 +/- 1.07 micrograms/ml vs. 22.64 +/- 1.05 mg/ml, p < 0.01) and throughout treatment duration (17.29 +/- 1.07 micrograms/ml vs. 21.85 +/- 0.78 microgram/ml, p < 0.01). CONCLUSIONS: Our findings confirm that in spite of continuous vancomycin infusion at an initial rate of 2 g/24 h, Staphylococcus aureus resistance to fosfomycin or fucidic acid an develop during ongoing treatment. Vancomycin levels of at least 20 micrograms/ml should be obtained as rapidly as possible.

[Bacterial adherence: virulence factor in upper urinary tract infections]. / Adhérence bactérienne: facteur de virulence dans les infections hautes de l'appareil urinaire.

The possibility that have certain strains of Escherichia coli to adhere to the urinary epithelium, constitutes a real pathogenic character. This adhesivity is specific and occurs through proteic structures (adhesins), that are present on the surface of bacteria and which recognize complementary receptors on uroepithelial cells. Studies of the frequency of these adhesins in different types of urinary tract infections, as well as experimental studies in animals all point towards an important role played by adhesins in the pathogenesis of the upper urinary tract infection.

Post-traumatic bone and/or joint limb infections due to Clostridium spp.

BACKGROUND: Clostridium spp. are saprophytic Gram-positive bacteria found in soil and capable of generating endospores. Spore germination occurs when environmental conditions are favorable. Clostridium spp. can cause infections of compound fractures and deep wounds contaminated from soil micro-organisms. HYPOTHESIS: Clostridium spp. infections of traffic-related injuries are particularly severe events whose outcome is uncertain even with aggressive medical and surgical treatment. MATERIALS AND METHODS: We retrospectively reviewed 12 patients (median age, 45 years) with Clostridium spp. bone and/or joint infections complicating compound limb fractures with soil contamination and extensive soft-tissue damage. Prophylactic amoxicillin-clavulanic acid therapy was administred, followed by emergency surgical wound debridment and lavage. Fracture fixation was performed immediately in nine patients (external in four and internal in five) or at a later time on three patients. The immediate outcome was unfavourable in all 12 cases, requiring early reoperation after a median of 10 days (range, 5-25 days). RESULTS: Median time to Clostridium strain identification was 14.5 days (range, 5-160). All infections were polymicrobial. Surgical wound excision, hardware removal (in four cases), and antibiotic therapy produced a favourable outcome in one patient, with no recurrence after 2 years of follow-up; the outcome was unfavourable in 11 cases, with delayed fracture union, septic non-union, impaired healing, and/or chronic sinus tract drainage. Several second-line treatments were used in these 11 patients: intramedullary nailing without bone grafting in four patients, with three failures; decortication and grafting in two patients, with failure in both; nailing with decortication in one patient, who had a good outcome; and the induced membrane procedure described by Masquelet in four patients, all of whom had good outcomes. After a median follow-up of 24 months (range, 18-53 months), the bone infection had subsided in eight patients. The remaining four patients had septic non-union. DISCUSSION: Clostridium spp. infections are particularly severe. The diagnosis is delayed and identification of the organism is challenging. The treatment is difficult and results in unfavorable outcomes in one-third of cases. The identification of Clostridium in specimens from an osteoarticular infection indicates a need for extremely extensive and aggressive surgical resection, as spore resistance may impair the in vivo efficacy of antimicrobial agents. LEVEL OF EVIDENCE: IV (retrospective cohort study).

Streptococcus milleri group infection associated with digestive fistula in patients with vascular graft: report of seven cases and review.

We described seven patients with Streptococcus milleri group aortic (six patients) or vena cava (one patient) graft infection secondary to a vasculo-digestive fistula. Time between vascular graft setting and first clinical signs varied from eight months to more than thirteen years. Six patients had fever. Three patients presented with recurrent fever for more than nine months and in two of these cases, delay before diagnosis was long because repeated blood cultures were sterile. Three patients had abdominal pain and/or digestive haemorrhage. Abdominal CT-scan S. milleri was not contributive for the diagnosis in four patients. Streptococcus anginosus was isolated in four patients, Streptococcus constellatus in three patients. One patient died before surgical management. The other six patients were cured by a surgical management associated with a prolonged antibiotic (lactams) treatment. S. milleri group graft infections are rare (or misdiagnosed) while we found only 4 similar cases in the English medical literature. We conclude that a peri-prosthetic infection secondary to a digestive fistula must be insistently searched (and blood cultures must be repeated many times) in any patient with an aortic (or any other vascular) graft presenting prolonged or recurrent fever or acute digestive symptoms.

[Open leg fracture with Bacillus cereus infection]. / Sepsis atypique à Bacillus cereus dans les fractures de jambe.

OBJECTIVE: To investigate leg fractures infected with Bacillus cereus in a traumatology-orthopedic ward of a university hospital. METHODS: All B. cereus strains isolated from patients with leg fracture hospitalized in the traumatology-orthopedic ward between 1995 and 2004 were included in this retrospective study. RESULTS: Five hundred and four patients had leg fracture during this period. Thirty-four patients were included in this retrospective study. B. cereus strains clinical isolates were mainly isolated from patients who had initially leg fractures with telluric contamination (wound contamination with terrestrial environments) before admission. Betalactam antibiotics used for prophylactic chemotherapy were not effective against B. cereus. CONCLUSION: In this study, we underscore the significance of Sfar recommendations concerning prophylactic chemotherapy. However, B. cereus could be termed an emerging pathogen and physicians need to be aware of its potential importance in trauma cases. In this purpose, a systematic screening for B. cereus at admission should be necessary in front of patients with open fractures associated with telluric contamination. Furthermore, if B. cereus is isolated, chemotherapy should be based upon ciprofloxacin during 2 or 6 weeks.

Detection by molecular hybridization of pap, afa, and sfa adherence systems in Escherichia coli strains associated with urinary and enteral infections.

The genetic determinants responsible for the adherence of Escherichia coli to uroepithelial cells have been identified in recent years by genetic and molecular methods. Specific DNA probes for each of the three operons which have been cloned so far (pap, afa, sfa/foc operons) have been used in colony hybridization experiments to detect the presence of each of these operons in the chromosomal DNA of 443 strains of E. coli; 186 strains were from patients with urinary tract infections (pyelonephritis, 106 strains; cystitis, 59; asymptomatic bacteriuria, 21) and 257 were strains from the stools of healthy subjects (61) or from patients with various enteral infections (196). E. coli strains harbouring the pap operon were found more frequently in the urine of patients with pyelonephritis (p less than 0.001) and cystitis (p less than 0.01) than in control stools. The presence of two operons (pap + afa) or (pap + sfa/foc) was only observed in uropathogenic strains (p less than 0.02). Pap and sfa/foc operons were never found in strains causing enteral infection; however, the afa operon was found in 7.6% of the enteropathogenic E. coli.

[Reflections on the systematic screening of cervico-vaginal smears rich in polynuclear cells]. / Réflexions à propos des frottis cervico-vaginaux systématiques de dépistage riches en polynucléaires.

The authors sometimes see cervico-vaginal smears with too many white cells. The question is: what is the meaning of these smears, and what must be the physician's attitude? The authors try to answer this question in this paper. They find 8 p. cent of genital tract infections in their observations.

[Bactericidal effect of cefotaxime-sulbactam and imipenem combined with gentamicin and/or ciprofloxacin against CTX-1 producing Klebsiella pneumoniae]. / Activité bactéricide de céfotaxime-sulbactam et imipénème associés à gentamicine et/ou ciprofloxacine sur Klebsiella pneumoniae, produisant CTX-1.

Bactericidal activity of gentamicin, imipenem, ciprofloxacin and cefotaxime associated with sulbactam are studied on 36 beta lactamase CTX-1 (TEM-3) producing Klebsiella pneumoniae strains isolated of sputum samples and urines, among patients of intensive care units, in Rangueil hospital (Toulouse). Gentamicin, imipenem, cefotaxime associated with sulbactam have a bactericidal activity at serum levels, obtained with usual therapeutic doses. Ciprofloxacin has a bactericidal activity at concentrations obtained in urine and into lung tissue. Killing curve method was used to study bactericidal activity of these antibiotics alone and in combination, on a representative sample. Alone gentamicin showed the most rapid bactericidal activity (2 hours). The associations with gentamicin are also rapidly bactericidal. The associations with ciprofloxacin and imipenem, ciprofloxacin and cefotaxime/sulbactam are synergistic.

[Haemagglutinins and adhesins of Escherichia coli strains isolated from urine: inhibitory effect of sub-inhibitory concentrations of tetracycline, doxycycline and minocycline. Preliminary results ]. / Hémagglutinines et adhésines des Escherichia coli isolés des urines. Effet inhibiteur du chlorhydrate de tétracycline, de doxycycline et de minocycline à concentrations sub-inhibitrices. Résultats préliminaires.

The present work concerned the study of the sub-minimal inhibitory doses of tetracyclin, doxycyclin and minocyclin on both hemagglutinating activity and adhesion capacity demonstrated in three E. coli strains isolated from urine. Two different types of hemagglutinins, mannose-resistant (HAMR) and mannose-sensitive (HAMS), were associated in two strains; HAMR was present in the third strain. Adhesion capacity was detected, in vitro, with uroepithelial cells spontaneously eliminated in urine. Whatever the antibiotic used, HAMR titers clearly decreased. In contrast, the effect of these antibiotics on the HAMS titers was inconstant, according to the bacterial strain or the antibiotic used. Adhesion capacity was inhibited particularly in the presence of tetracyclin and doxycyclin. Minocyclin was not a very good inhibitor molecule. The analysis of coefficient of correlation showed that the ability of adhering to uroepithelial cells was related to the HA titers. But it is impossible to say if the same bacterial structure migt be considered as mediator for both HA and adhesion capacity.

Rapid and specific detection of the pap, afa, and sfa adhesin-encoding operons in uropathogenic Escherichia coli strains by polymerase chain reaction.

Adhesin-encoding operons (pap, sfa/foc, and afa) have been shown to be prevalent in Escherichia coli strains associated with urinary tract infections. A quick and sensitive assay to identify these operons was developed by using the polymerase chain reaction (PCR). Three pairs of 25-mer primers were defined from the sequences of the DNA fragments used as probes in hybridization studies to identify each of the three operons, and the six primers were used together in a single reaction of amplification. To validate the PCR approach for detection of adhesin-encoding operons among clinical isolates, we investigated a collection of 97 E. coli isolates with the following characteristics: all isolates originated from the urine of patients with pyelonephritis, and the adhesin responsible for specific binding of the isolates to uroepithelial cells was previously characterized by phenotypic assays, as well as genotypic tests based on hybridization. There was a perfect correlation between the results obtained with the PCR approach and those previously obtained by using DNA probes. These results indicate that the PCR method, which is highly specific and easier to perform than the hybridization method, is a powerful genotypic assay for detection of adhesin-encoding operons. Thus, this assay can be recommended for clinical use to detect virulent urinary E. coli strains, as well as for epidemiological studies.

Phenotypic and genotypic assays for the detection and identification of adhesins from pyelonephritic Escherichia coli.

Four different gene clusters have been characterized so far which encode adhesins involved in the specific binding of pathogenic Escherichia coli to epithelial cells of the urinary tractus: the pap, sfa, afa and bma operons. The ability to adhere to uroepithelial cells and to interact with one or several of the specific receptors identified for each of the 4 adhesins, has been studied for 102 E. coli strains isolated from patients with pyelonephritis. These receptor-binding assays are referred to as phenotypic assays. Isolates which adhered to uroepithelial cells 68.6% produced at least 1 of the previously described adhesins. In addition, we used DNA probes to detect homologous sequences of the pap, sfa, and afa operons. Genotypic assays revealed that 87.2% of pyelonephretic E. coli contain DNA sequences related to at least 1 of the 4 operons; 78.4%, 22.5% and 11.8% of the strains harboured sequences related to pap, sfa and afa operons, respectively. The afa- and sfa-adhesion determinants were commonly found associated with the presence of the pap operon (8.8% and 18.6%, respectively). Detection of adhesins using the genotypic approach appears to be reliable (all adhesins detected using the phenotypic approach were also detected with probes). Detection by colony hybridization was significantly higher than by phenotypic assay. Discrepancies may have been due to absence of expression of the detected operons and may have resulted from improper in vitro growth conditions, phase variation, and/or heterogeneity of the genes encoding the adhesins within a family of related sequences.

[In vitro study of the effects of oxolinic acid at sub-inhibitory concentrations on the activity of hemagglutinins and adhesion to uroepithelial cells by Escherichia coli isolated from urine]. / Etude in vitro des effets de l'acide oxolinique à concentrations sub-inhibitrices sur l'activité des hémagglutinines et de l'adhésion aux cellules uro-épithéliales des Escherichia coli isolés des urines.

The aim of the present study was to investigate the effects of sub-MIC doses of oxolinic acid (quinolone), widely used in the treatment of urinary tract infections, on both haemagglutinating activity and adhesion capacity of 13 Escherichia coli strains isolated from urine during acute cystitis or pyelonephritis. All these strains adhered to uroepithelial cells and showed mannose-sensitive and/or mannose-resistant haemagglutinating activity. Sub-MIC doses of oxolinic acid induced filaments in most of the bacterial cultures; however, inhibition of haemagglutination and adhesion was variable in vitro. When inhibition did take place in any one strain, both haemagglutination and adhesion were affected. These results confirm those of other authors and indicate that the effect of sub-MIC doses of a given antibiotic is strain-specific; they also indirectly show the heterogeneity of E. coli strains isolated from urine. It thus seems unlikely that, in clinical conditions, a single antibiotic is capable of reducing adhesion, given the diversity of the adhesins found in pathogenic E. coli strains.

Possible in-vivo transfer of beta-lactamase TEM-3 from Klebsiella pneumoniae to Salmonella kedougou.

Salmonella kedougou BM2659 was isolated from the stools and a blood culture of a patient and Klebsiella pneumoniae BM2657 and S. kedougou BM2658 were isolated later from the stools of the same patient. Strains BM2657 and BM2658 had identical resistance phenotypes, to beta-lactams, aminoglycosides and tetracycline, due to the presence of the same genes, blaT, aacA4 and tetC, respectively. Oligotyping indicating that beta-lactam resistance in these strains was encoded by blaT-3 and synthesis of TEM-3 was confirmed by isoelectric focusing. In BM2657 and BM2658, the resistance characters were located on Inc7 or M self-transferable plasmids with indistinguishable EcoRI and HindIII restriction patterns. Southern hybridization of plasmid DNA of these strains with probes pCFFO4, the prototype plasmid encoding TEM-3, genes blaT, aacA4 and tetC gave identical patterns. S. kedougou BM2658 and BM2659 had identical biotypes and serotypes but BM2659 was susceptible to all the study antibiotics. These observations suggest possible transfer, in the digestive tract, of a plasmid encoding TEM-3 beta-lactamase from K. pneumoniae BM2657 to S. kedougou BM2659.

[In vitro activity of twenty antibiotics against Rhodococcus equi]. / Activité in vitro de vingt antibiotiques sur Rhodococcus equi.

The in vitro susceptibility of nine Rhodococcus equi strains (seven isolates from immunocompromised patients mainly HIV positive and two reference strains) to twenty various antibiotics were assessed for bacteriostatic effects by an agar dilution method. Imipenem and ceftriaxone were the most effective of the beta-lactams studied. The lowest MIC were noted with vancomycin, teicoplanin, erythromycin, clarithromycin, rifampicin, gentamicin and doxycycline. A longitudinal survey, including three strains isolated from the same patient, showed the emergence of rifampicin resistance and a marked increase of the MIC to imipenem.