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Biomedical subjects

M N Mallet

Publications and source records attributed to M N Mallet.

At least 37 records · Page 2Linked to original sources

[Extracellular and intracellular activity of sparfloxacin against Mycobacterium avium complex and Mycobacterium xenopi].

Activity of the new fluoroquinolone sparfloxacin against 30 strains of M. avium complex and 25 strains of M. xenopi was tested in vitro. Sparfloxacin was used alone (determination of MICs and MBCs) and in combination with ethambutol and rifabutin. Synergy studies with determination of the FIC and FBC indices showed that the sparfloxacin-ethambutol combination was synergistic against 10 M. avium complex strains and 12 M. xenopi strains. With the three-drug combination (sparfloxacin-ethambutol-rifabutin), synergy was found against 12 M. avium and 14 M. xenopi strains. Studies of intracellular bacteria showed that the decrease in viable bacteria with the three-drug combination was 1 log for M. avium and 2 log for M. xenopi.

Acquired Immunodeficiency Syndrome↗

Pharmacokinetics and tissue penetration of a single 1,000-milligram, intravenous dose of metronidazole for antibiotic prophylaxis of colorectal surgery.

The levels of metronidazole in serum and tissue penetration of metronidazole were studied after prophylactic administration in 11 patients undergoing elective colorectal surgery. A single dose of 1,000 mg given intravenously was administered before surgery. Adequate drug levels in serum (greater than or equal to MIC for 90% of strains tested [MIC90] for Bacteroides fragilis) were found in all patients throughout the procedure. Mean peak (15-min) and last-determined (24-h) metronidazole levels in serum were 28.8 +/- 8 and 4.2 +/- 1.7 mg/liter, respectively. The beta-phase elimination half-life was 9.5 +/- 2.3 h, and the clearance and apparent volume of distribution were 57 +/- 13 ml/min and 0.7 +/- 0.1 liter/kg, respectively. In the colonic wall at surgical anastomosis, tissue metronidazole levels greater than or equal to MIC90 for B. fragilis were found in 91% of patients. In the abdominal wall fat and epiploic fat, tissue metronidazole levels greater than or equal to MIC90 for B. fragilis were found in 40 to 60% of patients at surgical incision and closure. No anaerobic infection occurred during the study.

Aged↗

[Activity of antibiotics against pigmented and unpigmented variants of Mycobacterium avium-intracellulare].

Efficacy of various antibiotics: amikacin, rifampicin, rifabutin, ciprofloxacin, temafloxacin, erythromycin and clarithromycin was evaluated against pigmented and unpigmented variants of Mycobacterium avium complex isolated from patients with acquired immunodeficiency syndrome. The minimal inhibitory concentrations of antibiotics against unpigmented variants were multiplied by 2 to 16 compared to those of pigmented variants. Observations with intracellularly growing bacteria showed that unpigmented variants were more resistant to antibiotics than variants with a difference of approximately 0.25 a 0.3 log 10 in decrease of viable or bacterial counts. The combinations of temafloxacin or ciprofloxacin with rifabutin and amikacin were most effective against unpigmented variants.

Acquired Immunodeficiency Syndrome↗

[Intra-macrophagic activity of antibiotics combinations against Mycobacterium marinum].

Fourteen strains of Mycobacterium marinum were isolated from patients with granulomatous skin lesion. All the strains were resistant to isoniazid and pyrazinamid and five resistant to rifampicin. The following antibiotics are used alone or in combination: ethambutol, rifabutin, ciprofloxacin, temafloxacin, erythromycin, clarithromycin, minocyclin. Minimal inhibitory concentrations are evaluated using agar dilution method. After what, activity of antibiotics against Mycobacterium marinum strains within human macrophages in investigated. After treating the monolayers at 24 and 96 h, a bactericidal effect is observed with rifabutin, ciprofloxacin, temafloxacin, clarithromycin and minocyclin. Combinations of ciprofloxacin, temafloxacin or clarithromycin with ethambutol and rifabutin produced synergistic effect.

Anti-Infective Agents↗

[Pharmacokinetics and tissue penetration of single-dose netilmicin used for antibiotic prophylaxis during colo-rectal surgery].

Pharmacokinetics and tissue penetration of netilmicin were studied after the use of a single dose (6 mg/kg) given for antibioprophylaxis in colo-rectal surgery. Thirteen patients, scheduled for elective surgery, were given 6 mg/kg IV netilmicin over 30 min, together with 1000 mg IV ornidazole. Netilmicin peak serum concentration (10 min after end of infusion) was 24.4 +/- 3.4 mg/l and trough level (24 h) was 0.9 +/- 0.5 mg/l. Plasma elimination half-life was 409 +/- 70 min, le volume apparent volume of distribution was 38 +/- 101 and total body clearance was 0.07 +/- 0.02 ml/min. Adequate netilmicin levels (5 greater than or equal to CMI 90 of involved pathogens Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus) were obtained in 100 per cent of patients in abdominal wall and epiploid fat, at time of opening, and in colonic wall at time of anastomosis. Adequate levels were obtained at time of closure in abdominal wall and epiploid fat in 92 to 100 per cent of patients. In situation of allergy to beta-lactam antibiotics, the use of netilmicin in combination with ornidazole may be recommended.

Aged↗

[Diffusion of ciprofloxacin into bronchial secretions in mechanically ventilated patients].

The aim of the study was to evaluate, in clinical conditions, the penetration of ciprofloxacin into bronchial secretions. Eight patients were included in the study. They presented with nosocomial pneumonia and were under controlled mechanical ventilation. Ciprofloxacin was given at a dose of 3 mg/kg over 30 min. Serial bronchial and blood samples were obtained over a 12 hour period on day 2 and 4. Ciprofloxacin was measured by HPLC. Serum peak levels were 2.95 +/- 1 mg/l on day 2, and 2.43 +/- 0.7 mg/l on day 4. Bronchial peak and through levels were 0.95 +/- 0.51 mg/l and 0.21 +/- 0.12 mg/l, respectively, on day 2, and 0.76 +/- 0.17 mg/l and 0.18 +/- 0.14 mg/l, respectively, on day 4. The ratio of bronchial/serum peak was 0.32 +/- 0.11 and 0.33 +/- 0.06 on day 2 and 4, respectively. The ratio of AUC 0-12 h in the bronchial secretions/AUC 0-12 h in the serum samples was 0.66 +/- 0.04 and 0.55 +/- 0.27 on day 2 and 4, respectively.

Aged↗

[Value of systematic preventive antibiotherapy in cardiac pacemaker implantation].

The aim of this study was to assess the usefulness of prophylactic antibiotics during insertion of a cardiac pacemaker, in order to avoid infection of exteriorisation of infectious origin. The study involved two groups. One hundred and eight patients made up group I, a control group without the use of prophylactic antibiotics. Group II consisted of 101 patients who were given an intravenous injection of 1 or 2 g of oxacillin before surgery, followed up by four days of oral oxacillin (3 g per day). Serum oxacillin levels at the end of the procedure were 0.37 +/- 0.09 mcg/ml, falling within the range of minimum inhibitory concentrations of methicillin-sensitive staphylococci. In the patients of the control group, followed up for 1 to 36 months (mean 12 +/- 11 months), during the first 2 months there were 2 infections, 4 exteriorisations and one cutaneous erosion over the pacemaker. In addition, one exteriorisation and one infection occurred at 17 and 29 months respectively. In patients with exteriorisation of their pacemaker device, there was nothing to suggest an infection and bacteriological specimens were sterile. No obvious infections nor any cutaneous complications occurred in the patients of group II, with prophylactic antibiotics, followed up for 1 to 21 months (mean 6 +/- 5 months). In conclusion, anti-staphylococcal antibiotic treatment appears not only to be capable of avoiding cardiac pacemaker infections but also of preventing exteriorisation of the pacemaker device, which may be linked to hidden infections. A randomised study is nevertheless necessary to confirm this hypothesis.

Adult↗

Pharmacokinetics and tissue penetration of a single dose of ornidazole (1,000 milligrams intravenously) for antibiotic prophylaxis in colorectal surgery.

Levels in serum and tissue penetration of ornidazole were studied after a single intravenous injection of 1,000 mg given to 14 patients for prophylaxis of surgical infection. They were scheduled for elective colorectal surgery. Adequate levels in blood (greater than or equal to MIC for 90% of Bacteroides fragilis strains tested) were found in all patients throughout the procedure and up to hour 24. Mean-maximal (15 min) and last-determined (24 h) ornidazole levels in serum were 24 +/- 5.2 and 6.3 +/- 1.4 mg/liter, respectively. beta-Phase elimination half-life was 14.1 +/- 2.7 h, and clearance and apparent volume of distribution were 47 +/- 12 ml/min and 0.9 +/- 0.13 liters/kg, respectively. In all patient, adequate levels in tissue were found in the abdominal wall and the epiploic fat at time of incision and in the colonic wall at time of anastomosis. At time of closure, all but one patient had adequate levels in tissue in the abdominal wall and the epiploic fat. No anaerobic nor aerobic infection occurred in the study patients.

Aged↗

[Tissue penetration of single-dose cefotetan used for antibiotic prophylaxis in colorectal surgery].

Pharmacokinetics and tissue penetration of cefotetan were studied after a single injection of 2 g for antibiotic prophylaxis in colo-rectal surgery. Beta half-life was 4.3 +/- 1 h, total body clearance was 0.74 +/- 0.2 ml/kg/min and volume of distribution was 270 +/- 76 ml/kg. At time of laparotomy, cefotetan concentration was 14.2 +/- 7 micrograms/g in abdominal wall fat and 16.4 +/- 1 micrograms/g in epiploic fat. In the colonic wall, cefotetan concentration was 33.3 +/- 16 micrograms/g. At time of abdominal closure, cefotetan concentrations were 6.3 +/- 3 micrograms/g in the abdominal wall fat and 6.1 +/- 4 micrograms/g in the epiploic fat.

Abdominal Muscles↗

[Activity of azithromycin and roxithromycin alone or in combination against Mycobacterium avium and Mycobacterium xenopi].

The effect of two new macrolides, azithromycin and roxithromycin used either alone or in combination with amikacin rifabutine and 1.25 (HO)2 vitamin D3 was examined in vitro. Macrophage monolayers infected with M. avium complex or M. xenopi were treated with antibiotics or 1.25 (OH)2 vitamin D3 by using different protocols: antibiotics or 1.25 (OH)2 vitamin D3 was added to the macrophage monolayers immediately after infection and released by washing out after 24 h; antibiotics or 1.25 (OH)2 vitamin D3 was replenished daily for 4 days; or infected macrophage monolayers were treated with antibiotics plus vitamin D3 for 4 consecutive days. Treatment for 24 h resulted in an inhibition of growth. After treating the macrophage monolayers with the four antibiotics alone or in combination for 4 consecutive days intracellular killing of mycobacteria was observed and the combinations were significantly more lethal than antibiotics alone. The mycobactericidal effect was enhanced when vitamin D3 was added to the culture.

Azithromycin↗

[Post-antibiotic effect of imipenem, amikacin and ciprofloxacin against various strains of Serratia marcescens].

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.

Amikacin↗

Phagocyte-pathogen in the infected host.

Phagocytosis is a major mechanism of defense against bacterial infections. The ingestion of different microorganisms by blood granulocytes or monocytes may involve a variety of cell membrane recognition structures (e.g., immunoglobulin or complement receptors, lectin-like structures or other nonspecific binding sites). It is of interest to know which mechanism plays a prominent role in the management of a particular type of infection. Forty-three pathogenic bacterial suspensions were obtained from patients under mechanical ventilation at the onset of nosocomial lower respiratory tract infections. They were coincubated with blood granulocytes from the same or other patients in the presence or absence of the corresponding serum. Phagocytosis and the oxidative burst were then assayed. We conclude the following: a) Substantial phagocytosis was found under serum-free conditions and the patients' sera did not dramatically enhance bacterial uptake during the first days after the onset of clinical symptoms. b) The phagocytes from an infected patient did not display any peculiar inability to bind to the bacteria that grew successfully in this subject. Hence, the occurrence of a particular infection might be dependent on a defect of intracellular killing of ingested pathogens or on the conditions of infection development.

Adult↗

[Bacteriostatic and bactericidal study of rifabutine and clofazimine in combination against Mycobacterium avium-intracellulare and Mycobacterium xenopi].

The authors have tested the sensibility to rifabutine and clofazimine of seventeen strains of M. avium and eleven strains of M. xenopi. They compared the ability of these and other antimicrobial agents ciprofloxacin, amikacin and erythromycin alone or in combinations to inhibit the growth of strains of the M. avium complex and of M. xenopi. The purpose of this investigation was also to examine the bactericidal action of these antimicrobial agents and to determine the ability of combinations to kill strains of M. avium and M. xenopi.

Amikacin↗

[Antibiotherapy in gangrene of the perineum].

Fifty cases of extensive and necrotizing perineal cellulitis ("perineal gangrene") are reported. The disease, remarkable for its many anatomical and bacteriological varieties, is regarded as a therapeutic requiring multidisciplinary management. Bacteriological samples were polymicrobial in 40 cases. Streptococcus D and aerobic Gram-negative bacilli were isolated in 21 patients. The initial antibiotic treatment had to be modified on ten occasions in 36 patients who were given penicillin G in high doses and on five occasions in 14 patients who received a beta-lactam antibiotic active against anaerobes. Nineteen patients (38 p. 100) died; death was directly related to the sepsis in 16 cases. The death rate was the same in the two treatment groups (11/36 and 5/14) and similar to that found in the literature. The authors advocate an ureidopenicillin, fosfomycin and imidazole combination as a substitute for the conventional penicillin G, aminoglycoside, imidazole combination, since the former is active against Streptococcus D and has better tissue penetration.

Adult↗

Tobramycin dosing in mechanically ventilated patients. Inaccuracy of a 'rule of thumb'.

The ability of a simple rule of thumb, based on creatinine clearance, to predict tobramycin serum concentrations was evaluated in mechanically ventilated patients. They were given tobramycin intravenously over 30 min at 8 h intervals. Creatinine clearance was estimated from the formula developed by Cockcroft & Gault (1976, Nephron 16, 31-41) or was calculated after urine collection for 24 h. The loading dose was 1.5 mg/kg and then dose adjustments were performed on a daily basis. Patients were studied on day 1 and day 3. Mean values of peak and trough levels were within the therapeutic range, but individual values were outside the therapeutic range in 30% to 70% of patients on both day 1 and day 3, most of the patients having subtherapeutic serum concentrations. This was mainly related to the high volume of distribution of tobramycin calculated in these patients. These results further emphasize the need to monitor serum concentrations and to use an individual pharmacokinetic method to make dose adjustment.

Adult↗