Prolonged treatment of chronic Pseudomonas aeruginosa osteomyelitis with a combination of two effective antibiotics.

Emergence of Pseudomonas aeruginosa resistant to antibiotic monotherapy is one of the causes of therapeutic failure in chronic P. aeruginosa osteomyelitis. We report 15 cases of chronic (> 3 months of evolution) biopsy culture proven P. aeruginosa osteomyelitis included in an open prospective study evaluating the efficacy of prolonged treatment (> 4 months) with two effective antibiotics in combination. Mean post-treatment follow-up was 38 months. A regimen of cefsulodin in combination with oral ofloxacin was used for six patients, cefsulodin-pefloxacin for three patients, cefsulodin-ciprofloxacin for one patient, piperacillin-pefloxacin for one patient, cefsulodin-fosfomycin for one patient, imipenem-ciprofloxacin for two patients and amoxicillin-ciprofloxacin-fosfomycin for one patient as home therapy. The clinical cure rate of 73% and bacteriological cure rate of 93% are far superior to those previously described in the literature. We did not observe adverse drug reactions. We think that a prolonged use of two effective antibiotics in combination is a safe and improved therapeutic schedule for chronic P. aeruginosa osteomyelitis.

[Survey with three epidemiological markers after 22 cases of diarrhea caused by Clostridium difficile in a geriatric hospital]. / Enquête a l'aide de trois marqueurs épidémiologiques après 22 diarrhées a Clostridium difficle dans un hôpital gériatrique.

In a geriatric hospital of Saint-Etienne (Charité), among 153 patients having presented a nosocomial diarrhea from September 1990 to August 1991 Clostridium difficile (C.d.) has been isolated in 22 cases. Two of the nine units of the hospital had the highest incidence rates: 4.6 and 3.7%. In the faeces of 16 patients, C.d. was toxinogenic. In all cases, except one, antibiotic preceded diarrhea. Amoxicillin + clavulanic acid treatment was the most frequently responsible (65%). For detecting an eventual outbreak, several epidemiologic markers were evaluated: Clindamycin MIC, protein profiles, serotyping. Clindamycin susceptibility differentiated two Cd. types, but has no epidemiologic value. Protein profiles, performed by SDS-Page, individualized 6 different profiles, but 10 strains gave no classifiable profiles. Serotyping, applied by M. Delmée, appeared as the most interesting marker. Inquiry allowed to eliminate an outbreak but revealed two episodes of cross contaminations in the 3 units, 2 of them having the highest incidence rates. Markers proved persistence of the same C.d. strain in some patients who were correctly treated by metronidazole.

[Evaluation of three automated blood culture systems. Bio Argod, Bact T/Alert, bactec NR-860]. / Evaluation de trois systèmes automatisés pour hémocultures. Bio Argos, BacT/Alert, Bactec NR-860.

In 1991 and 1992, three automated blood culturing systems were successively assessed ("Diagnostics Pasteur" Bio Argos: 1,120 Vials, "Organon Teknika" BacT/Alert: 1,400 vials and "Becton Dickinson" bactec NR-860: 2,146 standard vials 6 and 7 and 2,360 resin vials 26 and 27), and compared with the conventional system (C) (Roche aerobic BHI-S Liquoîd, and Diagnostics Pasteur anaerobic prereduced Shaedler). Duplicate blood cultures were collected in various hospital services. They were processed over a 7-day period by the automated instruments and were incubated for 10 days using conventional techniques. The percentage of positivity (clinically significant results) obtained with the automated instruments was similar to that obtained with conventional techniques. Bio Argos: 3.4 p. cent vs 3.8 p. cent with C, BacT/Alert: 3.9 p. cent vs 3.5 p. cent, Bactec standard 6 and 7 vials: 5.6 p. cent vs 6.4 p. cent, and resin 26 and 27: 4.2 p. cent vs 3.1 p. cent. A better sensitivity was found with Bactec resin 26 and 27 vials when compared to C for Staphylococcus aureus (22 p. cent of S. aureus strains were isolated only with resin vials 26 and 27). False positives were as follow: 0.36 p. cent for BacT/Alert, 2.1 p. cent for Bio Argos and 3.5 p. cent for Bactec. The fastest detection rate was observed with the instrument which shakes the vials continuously (BacT/Alert): 73.6 p. cent of positive vials were detected on the day the vials were received at the laboratory. Ninety-four percent of the Bactec resin 26 and 27 positive vials, 90.6 p. cent of the BacT/Alert positive vials, 84 p. cent of the Bactec 6 and 7 positive vials and 73.7 p. cent of the Bio Argos positive vials were detected within twenty-four hours.

[Study of serum kinetics of vancomycin during the "antibiotic-lock" technique]. / Etude de la cinétique sérique de la vancomycine au décours de la technique de "blocage in situ".

The serum kinetics of vancomycin was studied in two patients aged 3 and 15 years during antibiotic therapy for catheter related sepsis associated with Staphylococcus epidermidis. Vancomycin was administered, simultaneously, by parenteral conventional doses (30 mg/kg/day div q 8 h) and using the antibiotic-lock technique in the infected catheter at a high concentration (150 mg/ml) during one hour, 3 hours after each infusion. Pharmacokinetics data did not show any significant change in the serum kinetics of the antibiotic. The results suggest that delivering a high concentration of vancomycin in the infected catheter using the lock technique may be useful to sterilize infected catheter without toxic effect.

Emergence of quinolone-imipenem cross-resistance in Pseudomonas aeruginosa after fluoroquinolone therapy.

Emergence of resistance to fluoroquinolones was observed in two clinical isolates of Pseudomonas aeruginosa after ciprofloxacin or norfloxacin monotherapy. In the first case, the resistant variants exhibited quinolone-imipenem cross-resistance (MIC of norfloxacin and ciprofloxacin: 16 mg/L; MIC of imipenem: 8 mg/L), although the patient had never received imipenem treatment, while the strain from the second case remained imipenem-susceptible (MIC of norfloxacin or ciprofloxacin: 8 mg/L; MIC of imipenem: 2 mg/I). The frequency of in-vitro emergence of variants resistant to imipenem and fluoroquinolones was studied for the two strains, with imipenem or fluoroquinolones as selecting agents. Ciprofloxacin and three other quinolones (norfloxacin, temafloxacin and tosufloxacin) selected imipenem-resistant variants in a similar way to imipenem for the first strain, but not for the other. In contrast, imipenem did not select quinolone-resistant variants from either strain. For both strains, killing curves demonstrated that a bactericidal effect could be obtained with a drug combination (2 x MIC of ciprofloxacin and 2 x MIC of imipenem) without any selection of resistant mutants after 24 h, thereby suggesting the possible use of this combined regimen for treating severe P. aeruginosa infection.

[Multifocal tuberculosis with cerebellar tuberculoma]. / Tuberculose multifocale avec tuberculome cérébelleux.

A 10-year old child was admitted for vomiting and a high grade fever. He had been previously immunized twice against tuberculosis. A cerebellar syndrome appeared, and the brain CT scan showed an intracerebellar mass. Disseminated lesions were detected on abdominal (splenic abscess) and thoracic (mediastinal lymph nodes) CT scans. The bone scintigraphy also showed multiple localisations. A craniotomy was performed that revealed a cerebellar tuberculoma which was completely removed. The child received an antituberculous treatment over 18 months and is currently well with a 5 year follow-up.

[In vitro bactericidal effect of temafloxacin and tosufloxacin against streptococci]. / Activité antibactérienne in vitro de la témafloxacine et de la tosufloxacine sur les streptocoques.

Tosufloxacin tosylate (TOSU) and temafloxacin hydrochloride (TEMA) were tested in vitro against 248 clinical isolates of various species of streptococci recovered in a hospital microbiology laboratory (Bellevue Regional Teaching Hospital). Species included S. pneumoniae (n = 20), group A streptococci (n = 22), group B streptococci (n = 30), group G streptococci (n = 17), group D S. bovis (n = 19), Enterococcus faecium (n = 45), Enterococcus faecalis (n = 28), S. sanguis (n = 21), S. milleri (n = 29) and S. mitis (n = 17). Activities of each of the two study drugs were evaluated comparatively with two other fluoroquinolones, i.e., ciprofloxacin (CIP) and pefloxacin (PEF). Activities of each of these four antibiotics, expressed as the MIC 90%, varied as follows according to the species of streptococci: TOSU, 0.25 to 1 mg/l, TEMA 0.5 to 2 mg/l, CIP, 1 to 4 mg/l and PEF 8 to 32 mgl. Overall, TOSU and TEMA exhibited the greatest activity of the various species. The size of the inoculum had no significant effect on MIC values.

[In vitro effect of new fluoroquinolones and betalactamines combinations against enterococci]. / Activité in vitro des associations de nouvelles fluoroquinolones et bêtalactamines sur des entérocoques.

Combinations of one of the new fluoroquinolones (ciprofloxacin, temafloxacin or tosufloxacin) with a betalactam (amoxicillin, piperacillin, or imipenem) were tested in vitro using the checkboard method against 28 strains of Streptococcus faecalis recovered in 1990 from a variety of specimens. No instance of antagonism (FIC greater than 2) was recorded. Effects of the two agents were usually additive (0.5 less than FIC less than or equal to 1). An indifferent effect (1 less than FIC less than or equal to 2) was seen in 32.1% of cases (9 strains) with the amoxicillin-tosufloxacin combination. Synergy (FIC less than or equal to 0.5) was uncommon with combinations including imipenem: effects were synergistic for only three strains with imipenem and either ciprofloxacin or tosufloxacin and for six strains with the imipenem-temafloxacin combination. Synergy was more common with combinations including ciprofloxacin and either piperacillin (10 strains, 35.7%) or amoxicillin (13 strains, 46.4%).

The penetration of ceftriaxone into human brain tissue.

The cerebral penetration of ceftriaxone in patients who underwent surgery for cerebral tumours was investigated. Seventeen patients received 2 g of ceftriaxone given intravenously 2 to 13 h before blood and brain samples were taken. Antibiotic levels were determined by an agar-well diffusion method. Cerebral ceftriaxone concentrations ranged from 0.3 to 12 micrograms/g, with a mean value of 1.63 micrograms/g. These values were less than 2% of corresponding serum concentrations, but enough to inhibit 75% of bacterial strains recently isolated from brain abscesses in our unit.

[Diffusion of ceftriaxone into the human brain]. / Diffusion de la ceftriaxone dans le cerveau humain.

Study of the penetration of ceftriaxone into the brain of patients who underwent surgery for cerebral tumors. Seventeen patients received 2 g of ceftriaxone intravenously 2 h to 13 h before blood and brain samples were taken. Ceftriaxone levels in serum and in non tumoral cerebral tissue were determined by the agar well diffusion technique. Hemoglobin concentration was measured in cerebral samples in order to subtract ceftriaxone due to blood contamination. True ceftriaxone levels in cerebral tissue ranged from 0.3 to 12 mcg/g, mean 1.63 mcg/g. The ceftriaxone level ratio in brain and serum was low, mean about 2%, but cerebral ceftriaxone concentrations would be sufficient to inhibit more than 75% of bacteria isolated in recent cerebral abscesses. These results allow to do further therapeutic studies of ceftriaxone in cerebral abscesses due to identified and susceptible bacteria or in random treatment in association with antibiotics directed on anaerobic organisms and resistant hospital strains.

[Appearance of Escherichia coli strain with high production of cephalosporinase during treatment with an amoxicillin and clavulanic acid combination]. / Emergence d'une souche d'Escherichia coli hyperproductrice de céphalosporinase au cours d'un traitement par l'association amoxicilline plus acide clavulanique.

In the course of an Escherichia coli cholecystitis, demonstrated by positive blood cultures, the authors observed a therapeutic failure with amoxicillin/clavulanate, probably related to the isolation in blood cultures, nine days after the beginning of the treatment, of a beta-lactam resistant E. coli strain (MICs of the amoxicillin combined with clavulanate was 64 mg/l and ceftazidim 16 mg/l). The strains which were recovered before and after treatment were shown to have the same biotype and the same electrophoretic profile for bacterial esterases. The second strain exhibited a high level production of the mediated chromosomal cephalosporinase. In the agar diffusion test, this mutant was more easily detected by ceftazidim than by other third generation cephalosporins. In the middle-stay unit where the patient was cured, cephalosporinase high producing mutants of E. coli were recovered in 0.6 p. cent of the strains versus 5, 1 p. cent for strains with cephalosporinase phenotype and 46.6 p. cent for strains with penicillinase phenotype. This report illustrates the importance of associating two synergistic antibiotics to prevent the emergence of beta-lactam resistant mutants in the course of severe E. coli infections.

[Activity of 5 fluoroquinolones on hospital Gram-negative bacilli with different sensitivities to pefloxacin]. / Activité de cinq fluoroquinolones sur les bacilles à Gram négatif hospitaliers de différentes sensibilités à la péfloxacine.

The minimum inhibitory concentrations (MIC) of 5 fluoroquinolones, fleroxacin (FLE), ciprofloxacin (CIP), ofloxacin (OFL), enoxacin (ENO) and norfloxacin (NOR) have been determined by the agar dilution method towards 140 strains of Pseudomonas aeruginosa (Pa) and 146 Enterobacteriaceae showing different sensitivities to pefloxacin (PEF). The strains were isolated in 1988 at the Bellevue Hospital. The modal MIC is 0.12 for CIP, 0.25 for NOR, 0.5 for OFL, and 1 for FLE and ENO when used on Pa strains which are sensitive to PEF (n = 35) (MIC less than or equal to 1mg/1). The modal MIC is 0.25 - 0.5 for CIP, 0.5 for NOR, 1 for OFL and ENO, and 2 for FLE when used on Pa strains which are of intermediate sensitivity to PEF (n = 70) (1 less than MIC less than or equal to 4). The modal MIC is 2 for CIP, 8 for NOR and OFL, 8 - 16 for ENO, and 32 for FLE when used on Pa strains which are resistant to PEF (n = 35) (MIC greater than 4). The modal MIC is 0.015 for CIP, 0.06 for OFL, 0.12 for FLE, NOR and ENO when used on Escherichia coli strains which are sensitive to PEF (n = 47). The modal MIC is 0.5 for CIP, 1 for OFL and NOR, and 2 FLE and ENO, when used on Escherichia coli strains which are of intermediate sensitivity to PEF (n = 38). The modal MIC is 1 for CIP, 4 for OFL and NOR, 16 for FLE, and 32 for ENO when used on E coli strains which are resistant to PEF (n = 15). The 26 Serratia marcescens and 20 Citrobacter with MIC greater than or equal to 8 for PEF all have MICs greater than 1 and modal MICs greater than or equal to 4 for all the fluoroquinolones studied. CIP always showed greater activity than the other quinolones whatever the sensitivity shown towards PEF.

[Comparative study of a combination of amoxicillin and clavulanic acid and a combination of ticarcillin and clavulanic acid on 249 enterobacteria]. / Etude comparative entre l'association amoxicilline-acide clavulanique et l'association ticarcilline-acide clavulanique sur 249 entérobactéries.

A comparison between the MIC of amoxicillin (AMX) and ticarcillin (TIC) in the presence of clavulanic acid (Augmentin: AUG and Claventin: CLV) was made on 168 strains of Escherichia coli resistant to amoxicillin (MIC greater than 16 mg/l) and yet sensitive to ceftriaxone (MIC less than or equal to 4 mg/l) and 81 strains of Klebsiella pneumoniae sensitive to Ceftriaxone. All those strains have been isolated between 1986-87 in Bellevue Hospital in Saint-Etienne. On 168 Escherichia coli, 142 have a MIC greater than 128 mg/l of TIC. Those 142 Escherichia coli are sensitive or of an intermediary sensitivity to Cephalothin (MIC less than or equal to 32 mg/l) in 57% cases. Those 142 strains are sensitive to AUG (MIC less than or equal to 4 mg/l) in 13.4% cases, intermediary sensitive to AUG (4 less than MIC less than or equal to 16) in 30.3% cases, sensitive to CLV (CMI less than or equal to 16 mg/l) in 23.3% cases and intermediary sensitive to Claventin (16 less than MIC less than or equal to 64) in 47.2% cases. The 26 Escherichia coli of MIC less than or equal to 64 mg/l of TIC and resistant to Cephalothin (MIC greater than 32 mg/l) have MIC less than or equal to 4 mg/l of AUG In 3.8% cases and MIC less than or equal to 16 mg/l of Claventin in 79.6% cases. The 81 Klebsiella pneumoniae

[Activity of ticarcillin combined with different concentrations of clavulanic acid on 137 Gram-negative bacilli resistant to ticarcillin]. / Activité de la ticarcilline associée à différentes concentrations d'acide clavulanique sur 137 bacilles Gram négatif résistant à la ticarcilline.

The MIC of ticarcillin exclusively or joined with 3 concentrations of clavulanic acid: (2, 4 and 8 mg/l) was determined by agar dilution in relation to 137 bacilli resistant to ticarcillin (MIC greater than or equal to 256 mg/l) detected between 1985 and 1986 in the Bellevue Hospital in Saint-Etienne. We could study 26 Escherichia coli, 30 Klebsiella, 28 Enterobacter, 36 Serratia and 17 Pseudomonas aeruginosa. The concentration of 2 mg/l of clavulanic acid allows to lower the MIC of ticarcillin over the very large majority of strains of Escherichia coli and Klebsiella resistant to ticarcillin. In those conditions, ticarcillin becomes more active than piperacillin over those species. The concentration of 4 and 8 mg/l of clavulanic acid doesn't bring any real advantage to those bacilli. Moreover the concentrations of 2, 4 and 8 mg/l slightly change the MIC of ticarcillin on the strains of Serratia, Enterobacter and Pseudomonas aeruginosa.