Cefotaxime (C) vs cefotaxime + amikacin (C + A) in the treatment of septicemia due to enterobacteria: a multicenter study.
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Biomedical subjects
Publications and source records attributed to F Vachon.
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In 12 patients infected with an Enterobacter cloacae (E. cl.) initially susceptible to the 3rd generation cephalosporins, we observed the emergence in vivo of variants resistant to most of the new beta-lactam antibiotics (carboxy-penicillins, ureido-penicillins, 3rd generation cephalosporins and aztreonam). These variants remained susceptible to mecillinam and imipenem. The variant emerged under treatment with cefotaxime in 3 cases, with moxalactam in 3 cases, with aztreonam, carbenicillin, and ticarcillin in 1 case each and without treatment in 1 case. An aminoglycoside was combined with the beta-lactam antibiotic in 6 cases. Therapeutic failure was attributed to emergence of the resistant variant in 6 out of 12 cases (with an aminoglycoside in 3 cases, with the beta-lactam antibiotic alone in 3 cases). These case reports underline the importance of bacteriological monitoring of patients infected with E. cl. treated with a beta-lactam antibiotic. The susceptibility to beta-lactam antibiotics of the E. cl. strains isolated during treatment should be systematically retested.
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The therapeutic effectiveness of pefloxacin was evaluated in 15 patients admitted to an intensive care unit and suffering from septicaemia or endocarditis. Seven of these patients had a focal infection (acute anterior mediastinitis or epiduritis). Pefloxacin was combined with an aminoglycoside in 13 cases and with rifampicin in 1 case. Blood cultures became or remained negative in all patients. The associated focus of infection was sterilized in 5 patients; a pefloxacin-resistant pathogen was subsequently isolated in 2 other patients. Three patients died some time after the infectious episode. The minimum inhibitory concentration of pefloxacin ranged from 0.25 to 2 mg/l. The bactericidal activity of the serum at peak concentration was greater than or equal to 1/8 in all cases and greater than or equal to 1/32 in 10 cases. No resistant mutants were selected during treatment. However, 8 strains of a species different from that of the initial pathogen were isolated from a site other than the primary focus. Pefloxacin can therefore be used successfully in the treatment of systemic infections, but close monitoring of bacterial ecology is required.
Twenty-two patients admitted to the ICU with a severe nosocomial infection caused by multi-resistant Gram-negative bacilli were treated with imipenem combined with cilastatin. We treated nine cases of meningo-ventriculitis, eight cases of septicaemia, four cases of mediastinitis, and one case of pneumonia. The bacteria responsible were Acinetobacter spp. (10), Pseudomonas aeruginosa (5), Enterobacter cloacae (5), Klebsiella pneumoniae (3), Proteus spp. (2), Streptococcus spp. (2), Serratia marcescens (1). More than one pathogen was isolated in five cases. The dosages ranged between 1.5 g to 4 g per day by intravenous infusion; the highest doses were used for the treatment of meningitis. The mean duration of treatment was 17 days. An aminoglycoside was combined with imipenem in 18 cases. Cure was obtained in 17 out of the 22 cases. Very rapid sterilization of the CSF in the cases of meningitis and ventriculitis was noted. Two patients died rapidly despite eradication of the bacteria. One case of meningitis relapsed but cure was subsequently obtained with continuation of the same treatment. In three cases of Ps. aeruginosa infection, resistant mutants were isolated from the sites of infection and were responsible for two failures and one colonization. Imipenem appears to be an antibiotic of choice in severe nosocomial infections including meningo-ventriculitis, especially those caused by Acinetobacter spp. and Ps. aeruginosa. It is also one of the few antibiotics active against both streptococci and multi-resistant Gram-negative bacilli. Careful bacteriological monitoring is recommended during treatment.
The use of preventive antibiotic therapy to reduce frequency and severity of infections related to certain surgical acts still remains a subject of polemic and confusion. The need to employ definitions and therefore a common language to arrive at a consensus in each surgical team and for each surgical procedure is emphasized. The major principles guiding bacteriologic objectives are discussed, as well as the choice of corresponding antibiotic and its mode of administration.
The report describes a simple effective system of meeting the oxygen requirements of tracheostomized infants in the home setting. It consists of oxygen tubing which may be run under the infant's clothing and connected to the tracheostomy tube through a specially created hole. This allows a continuous administration of oxygen while minimizing the risk of accidental decannulation of disconnection by the infant grabbing the oxygen tubing. This has been used successfully in the management of infants with tracheostomies and chronic oxygen needs due to bronchopulmonary dysplasia.
N-methylglucamine antimoniate (Glucantime) is used to treat visceral leishmaniasis but may give rise to serious and sometimes lethal complications: cardiac, hepatic, renal and haematological disease. These may be prevented by respecting the maximal suggested dosage of 6 cg/kg/day, regular clinical checks of pulse, blood pressure and temperature, biological follow-up of serum creatinin, transaminases and routine electrocardiography.
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Prior to the introduction of new beta-lactam antibiotics, such as ureidopenicillins and some third generation cephalosporins, the choice of antibiotics for the treatment of meningitis caused by Ps. aeruginosa was limited, and even now, this infection remains of poor prognosis. Five patients with meningitis, aged from 18 to 75 years, were treated with azlocillin. The strains of Ps. aeruginosa isolated were all sensitive to azlocillin, the zones of inhibition being greater than 20 mm in diameter with bacteriostatic concentrations. Azlocillin was administered 8-hourly by intravenous injection in doses of 30 g/day in 3 cases and 15 g/day in 2 cases. The mean duration of treatment was 33 days (range 23-50 days). In addition to azlocillin 4 patients received an aminoglycoside (tobramycin or amikacin) parenterally and, in one case, intrathecally. Four patients underwent a surgical operation on the focus of infection between the 9th and 13th days of treatment. In 3 of these 4 patients surgery was necessary to obtain apyrexia, but in all cases the CSF was already sterile when it was performed. The outcome was favourable in all 5 cases. One patient relapsed on 4 occasions due to persistent petrous bone fistula; each time, the azlocillin treatment was reinstituted and brought about clinical and bacteriological cure. The germ was eradicated in CSF on the 3rd day of treatment in 3 patients and on the 7th day in one. One patient developed transient eosinophilia and another, transient neutropenia after 30 days. It is concluded that azlocillin, associated with an aminoglycoside, is an active and effective antibiotic for the treatment of Ps. aeruginosa meningitis.
Six cases of chronic endocarditis (more than 1 year duration) have been extracted from a series of 72 cases of endocarditis (delayed in 49) associated with intracardiac prosthesis observed over a 15-year period. In these 6 cases endocarditis developed 6 months to 2 years after valve replacement. The prosthetic material included 3 Starr-Edward's valves, 2 Hancock's valves and 1 intracardiac patch. The micro-organism isolated were Streptococcus in 3 cases, Serratia and Corynebacterium in 1 case each. The 18-month to 5-year course of the disease was marked by 2 to 5 relapses separated by long periods of apyrexia. The most significant complications were dysimmune syndrome (5 cases), embolic accidents (2 cases) and prosthesis disinsertion (4 cases). Five patients benefited from antibiotic therapy; 4 were operated upon with recurrent disinsertion in 2 cases. Two patients died, one of repeated disinsertion, the other of myocardial dysfunction. Bacteriostatic antibiotics were administered continuously to 3 patients whose endocarditis persisted or relapsed, with satisfactory results in two cases followed-up for more than 2 years.
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Fifty six cases of tricuspid infective endocarditis (TIE) were seen over a period of 15 years. The patients were divided into three groups, on the basis of the site of entry: (a) Thirty one TIE after abortion (6 cases) or in association with drug addiction (25 cases) are characterized by the young age of the patients and the organism (29 staphylococci), the existence of repeated pulmonary emboli and the relatively favourable prognosis (3 deaths). (b) Twelve TIE due to an intravenous infusion catheter (9 cases) or a visceral site of entry: older patients, resistant organisms (3 gram negative bacilli, 8 staphylococci, 5 of which were methicillin-resistant) and with poor prognosis (8 deaths). (c) Thirteen TIE where the site of entry was unidentified, running a sub-acute course, 7 due to streptococci, and often associated with involvement of the left side of the heart, which was the dominant prognostic feature (6 deaths). Mortality was 30%. Of predominant importance in prognosis was the sensitivity of the organism: 6 deaths out of 9 TIE due to methicillin-resistant Staphylococcus aureus and 3 out of 31 TIE due to a sensitive staphylococcus (P less than 0.01). Seventeen underwent surgery. Tricuspidectomy (8 patients) should be reserved for cases of uncontrolled infection. Surgery is not justified by the persistence of pulmonary emboli.
Among 369 patients with native valve infective endocarditis observed during a 14-year period, 17 were related to S: pneumoniae. Fourteen of them were observed in the last 7 years. At the time of admission 13 exhibited purulent meningitis, 6 of them being comatose. An apparent portal of entry was present in 13 patients including Pneumonia (n = 11) and otitis media (n = 2). Major alcoholism was present in 6 cases. The mean delay between the onset of fever and the discovery of the cardiac murmur was 15 days (range 1 to 60). Twelve patients exhibited congestive heart failure with acute pulmonary oedema in 9. The aortic valve was involved in 12 and the mitral valve in 7 (in 2 patients both mitral and aortic valves were involved). Myocardial and/or annular abscesses were found in 7 patients. Nine patients underwent surgical procedure (3 died) whereas 6 comatose patients were not operated on and died. The overall mortality was 59%. Although antibiotics are effective, the severity of anatomical lesions leads to prompt surgical treatment. The high mortality is mainly due to purulent meningitis.
Peak and trough vancomycin serum levels were measured in 37 severely ill patients following dosing using the Moellering nomogram. The peak and trough serum concentrations were 61.2 +/- 23 and 22.6 +/- 16.5 mg/l, respectively, and higher than expected. Vancomycin pharmacokinetics obtained from 10 other patients were also studied. In five patients with a creatinine clearance greater than 1 ml min-1 kg-1, a mean plasma elimination half-life of 7.8 +/- 2.8 h was calculated. In the five other patients with markedly reduced renal function (creatinine clearance less than or equal to 1 ml min-1 kg-1), the mean elimination half-life was 18.3 +/- 10.2 h. A correlation was observed between the vancomycin and creatinine clearance. Important inter-patient variations of vancomycin clearance for the same creatinine clearance was also noted. Tubular damage in critically ill patients with severe sepsis may explain our results of the decreased vancomycin elimination.
We evaluated the diffusion of pefloxacin into the cerebrospinal fluid (CSF) in 15 patients with bacterial meningitis or ventriculitis, 14 of whom were treated with other antibiotics. Three doses of pefloxacin were administered at 12-h intervals to 11 patients intravenously and to 4 patients orally. Individual doses were 7.5 mg/kg in seven patients and 15 mg/kg in eight patients. Plasma and CSF levels were determined by a high-performance liquid chromatographic assay. The concentrations of pefloxacin in CSF were measured 2 h after the third intravenous dose and 4 h after the third oral dose. In patients receiving 7.5 mg/kg, peak levels in plasma ranged from 6.8 to 16 micrograms/ml, and trough levels were from 2 to 7.5 micrograms/ml. Concentrations in CSF ranged from 2.4 to 9 micrograms/ml. In patients receiving 15 mg/kg, peak levels in plasma ranged from 14 to 18.6 micrograms/ml, and trough levels were from 4 to 13.2 micrograms/ml. Concentrations in CSF ranged from 6.5 to 13 micrograms/ml. These preliminary data indicate that pefloxacin diffuses well into the CSF of patients with inflamed meninges.