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We have collected cases of iatrogenic meningitis managed in the Children's Hospital of Tunis, between January 1998 and December 2006. Clinical information about each patient were collected, all bacterial samples were investigated in the microbiology laboratory of the hospital. Bacterial isolates were identified according to conventional criteria. In the interval under study, we recorded three cases of iatrogenic meningitis after lumbar puncture. Two cases occurred in newborn admitted for suspicion of neonatal infection and one in a 2-month-old infant admitted for exploration of hyperpyretic convulsion. In all patients, the initial cerebrospinal fluid was normal. All patients developed symptoms of acute meningitis within 72 hours after lumbar puncture; the second cerebrospinal fluid was, then, typical for purulent meningitis. The causal agents isolated in the three cases were Klebsiella pneumoniae, Enterobacter cloacae, and Serratia marcescens, all resistant to beta-lactams by extended spectrum beta-lactamase production. The use of quinolones was required in all cases. Different complications were recorded: hydrocephalus and brain abscess in one case, respiratory and hemodynamic failure managed in the intensive care unit in the second, and brain hygroma in the third case. This study shows high morbidity of iatrogenic meningitis. Simple aseptic precautions undertaken before the procedure of lumbar puncture can prevent such cases. The urgent need for increasing the awareness among medical personnel in hospitals of developing countries cannot be overemphasized.

Imipenem is a beta-lactam antibiotic active against most Gram-negative bacilli. Between July 1, 1987 and September 30, 1989 (9 semesters), the activity of imipenem against 6 micro-organisms was tested in two intensive care units attached to the university hospital of Caen (Normandy). During the same period, the consumption of imipenem was evaluated from the number of vials drawn by each of these two units from the central pharmacy. Imipenem was found to be 100 percent effective against 5 of the 6 micro-organisms tested, but transient falls in sensitivity and an increase in imipenem consumption were observed when Pseudomonas aeruginosa was the pathogen. The most probable cause of these transient decreases of imipenem activity against Ps. aeruginosa was the existence of a resistant strain which showed a protein abnormality in its outer membrane by temporary selection pressure.

The authors compared the post-antibiotic effect (PAE) of imipenem, amikacin, ciprofloxacin, and latamoxef against Serratia marcescens ATCC 13880 (type strain) and against 12 clinical strains belonging to Grimont's most frequent biotypes: A2a, A3a, A3b, A4a, A4b, A5, A6a, A8a, A8b, A8c, TT, TCT. PAE was determined by measuring bacterial growth kinetics after one hour exposure to concentration of 2 x MIC of 10(6) CFUs in Mueller-Hinton broth. Drug removal was by 10-3 dilution of the exposed culture. A PAE was consistently present with imipenem (range 0.8-2.9 hrs), amikacin (range 1.0-4.9 hrs), ciprofloxacin (range 1.4-2.8 hrs). The duration of PAE did not correlate with MIC or Grimont's biotypes.

The mechanisms of resistance to fosfomycin which, at the present, predominate among clinical isolates of Serratia marcescens as well as the incidence and dispersion of For plasmids among other species of Enterobacteriaceae were studied. It was found that that 23 of the 29 strains under study phenotypically behaved as glp T- mutants, another as glp T- and uhp- and five of them showed no alterations in their transport system. Self-transferable plasmids involved in For were isolated from the latter. For plasmids were also found in strains of Klebsiella pneumoniae but not in other enterobacteria. Plasmids were studied in order to establish their resistance phenotype, molecular weight and incompatibility group. The data obtained along with the restriction pattern allow us to conclude that the trait For is linked to, at least, two different replicons.

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.

The minimal inhibitory concentrations (MIC) of gentamicin for ten strains of Enterobacteriaceae were determined by measuring the bacterial ATP (adenosine triphosphate). ATP was measured by chemiluminescence on 4-h growth cultures which included gentamicin. The MIC results obtained by this method were equivalent to those found with the technique of dilution in liquid medium.

The bactericidal activity of cefotaxime against Escherichia coli, Klebsiella pneumoniae and Serratia marcescens, was compared with that of cefixime in an in vitro model simulating the human pharmacokinetics of these antibiotics. Kinetic parameters in this model were T1/2 = 1.3 h and Cmax = 45 mg/l for cefotaxime; T1/2 = 3.5 h and Cmax = 5 or 3.5 mg/l for cefixime. These parameters mimicked those obtained after a 1 g intravenous infusion of cefotaxime and an oral uptake of 0.4 or 0.2 g of cefixime, respectively. Both antibiotics demonstrated a strong bactericidal activity. Against Escherichia coli, the bactericidal effect of cefotaxime was slightly more rapid and more prolonged than that of cefixime: -5 log10 CFU/ml over 4 h vs -3 log10 CFU/ml over 8 h respectively. Against Klebsiella pneumoniae and Serratia marcescens, both drugs exhibited similar bactericidal activity despite different dosages and routes of administration: -2 to -3 log10 CFU/ml over 4 h.

Combinations of piperacillin (PIP) with 3 systemic fluoroquinolones: pefloxacin (PEF), ofloxacin (OFL) and ciprofloxacin (CIP) were evaluated by checkerboard technique (bacteriostatic activity) and by time-killing curve technique (bactericidal activity as a function of time) for 4 bacterial strains with following MICs (micrograms/ml): 1 E. coli (PIP: 1, PEF: 0.12, OFL: 0.06, CIP: 0.016); 1 S. marcescens (0.25, 0.06, 0.06, 0.016); 2 P. aeruginosa (2, 1, 0.5, 0.12 and 4, 2, 2, 0.25). Bacteriostatic activity of the 3 combinations showed only different or additive effects (index FIC: 0.62 to 1.5). If the bactericidal activity was defined as a less than or equal to 3 log 10 decrease in CFU/ml in 3-6 h and less than or equal to 4 log 10 in 6-24 h, PIP was not bactericidal at MIC x 8 for all strains; nevertheless, combinations of PIP 2 + PEF 0.25, OFL 0.12 or CIP 0.016 on E. coli and PIP 1 + PEF 0.25, OFL 0.25 or CIP 0.06 on S. marcescens showed bactericidal activity, superior to each antibiotic singly. For P. aeruginosa a less than or equal to 4 log 10 decrease in 6-24 h was observed only in combination with PIP 16 + PEF 1, OFL 1 or CIP 0.25 and PIP 32 + PEF 4, OFL 4 or CIP 0.5. Combinations of PIP with quinolones showed synergistic effects: bactericidal activity was more rapid and prolonged with such combinations at concentrations near MICs and obtained with usual therapeutic doses.

Bactericidal activity of cefotetan-gentamicin combinations was studied on 6 bacterial strains: S. aureus, K. pneumoniae, E. cloacae, S. marcescens, P. vulgaris, P. stuarti. Time kille curves technic was performed with final concentrations of cefotetan: 4 at 32 mg/l, and of gentamicin: 0.25; 0.5; 1; 2; 8 mg/l and with an 10(6) CFU/ml inoculum. Cefotetan at 4 mg/l was not able to obtain a 0.01% (percentage of survivors) bactericidal activity before 24 h. The combination cefotetan-gentamicin (0.25 to 2 mg/l according to the strains) were bactericidal (0.01% of survivors) before 24 h: 1 to 6 h according to the strains, more rapidly than with gentamicin alone at the same concentration. This more rapid bactericidal activity obtained by cefotetan-gentamicin combination seems to indicate this combination in the treatment of severe infections in immunocompromised patients.

The prevalence of Pseudomonas aeruginosa in intensive care unit (ICU) is 19 per cent although its incidence in blood culture is only 3.5 per cent and remains the same even though the total prevalence of this bacterium increases. A review of the clinical results shows that this germ causes severe complications in only 3 per cent of patients. A study by epidemiological markers reveals the presence of 16 different IATS serotypes in the ICU, this distribution of the serotypes being similar to this observed in ambulatory patients. The serotype 12 of Ps. aeruginosa is multiresistant. In 1984, it represented 22 per cent of the isolated Ps. aeruginosa, its incidence decreases in 1985 and in 1986 (14.5%). Ps. aeruginosa seems weakly pathogenic for the surgical patients in the ICU. On the other hand, the incidence of Klebsiella pneumoniae, Serratia marcescens (014 imm. serotype resistant to tobramycin), Enterobacter aerogenes and Enterobacter cloacae increases in blood cultures proportionally to their total prevalence in ICU. These bacteria are probably responsible for hospital epidemics.

A strain of Byssochlamys nivea cultivated in a liquid medium (Saccharose: 50 g: NaNo3: 2 g; KH2PO4: 1 g; KCL: 0.5 g; MgSO4, 7H2O: 0.5 g; water to 1000 ml) produces, at 24 degrees C, an antibiotic substance which appears after several days of growth (10-12 days). Among 43 strains of Bacteria Gram (minus) belonging to 10 genera none was resistant. The most was susceptible, save Pseudomonas aeruginosa, Serratia marcescens, Moraxella glucidolytica. On the the great bulk of the Bacteria (Gram +) tested was little influenced, except certain strains of Bacillus. The filtrate is ineffectual against Mycobacteria and Fungi (yeast or mould) at the concentration used. This substance seemed to be different of those produced by Byssochlamys fluva (byssochlamic acid) and by some species of Paecilomyces (P. varioti, P. persicinus, P. elegans, P. variabilis, P. fusidioides).