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Biomedical subjects

J Kosmidis

Publications and source records attributed to J Kosmidis.

At least 37 records · Page 2Linked to original sources

Ticarcillin and clavulanic acid in serious infections.

In an open, non-comparative study 40 patients with severe, often life-threatening infections, were treated with Timentin 5.2 g (5 g ticarcillin plus 200 mg potassium clavulanate) by iv infusion every 6 or 8 h. They were suffering from septicaemia (9), obstructed UTI (8), non-obstructed urinary tract infection (10), respiratory tract infection (6), infected burns (4) or malignant otitis externa (3). Many patients had important aggravating factors such as renal transplantation, peritoneal or haemodialysis, leukaemia, extensive burns, renal stones, tracheostomy and diabetes. Pathogens included Pseudomonas aeruginosa (21), Escherichia coli (7), and other Enterobacteriaceae (6). Twenty-four pathogens (13 P. aeruginosa) were ticarcillin-resistant. Thirty-six patients were clinically cured including all cases of malignant otitis externa, infected burns and non-obstructed urinary tract infection. Three patients improved and one patient with obstructed urinary tract infection failed. In 32 patients the pathogen was eradicated, in one patient it persisted and in seven it reappeared. In particular, 11 of 13 patients with infections due to ticarcillin-resistant P. aeruginosa were cured and two improved. There was, however, bacteriological relapse in five. There were no side-effects or evidence of toxicity in any of the patients. In an in-vitro study a synergistic effect between ticarcillin and clavulanate was noted against Enterobacteriaceae but only a slight synergistic effect against P. aeruginosa. Studies in patients with normal liver and kidney function showed pharmacokinetic compatibility of the two agents. Timentin can be recommended for the initial treatment of serious infections.

Adult↗

Emergence of resistant bacterial strains during treatment of infections in the respiratory tract.

In order to investigate the frequency of the emergence of resistance during treatment, 1,403 episodes of lower respiratory infection were studied in a General Hospital with three departments of Chest Medicine in a period of four years. In 650 episodes the pathogen was isolated and in 82 of those failure of therapy was accompanied by emergence of resistance to the agent used. Factors associated with this phenomenon were: intensive care, tracheostomy, involvement of Pseudomonas aeruginosa, Enterobacter spp., Serratia marcescens, Staphylococcus aureus or Acinetobacter calcoaceticus, use of antipseudomonas penicillins, cefotaxime (especially when used in P. aeruginosa infections) and co-trimoxazole and monotherapy as opposed to appropriate combination therapy in patients with nosocomial pneumonia.

Acinetobacter↗

The treatment of complicated and uncomplicated urinary tract infections with temocillin.

Temocillin was given to 33 patients with urinary tract infection as a once daily dosage regimen of 500mg intramuscularly or Ig intravenously for 7 to 10 days. The lower dose produced a clinical cure in 83% of patients with uncomplicated infection but was ineffective in complicated cases, whereas the higher dose cured 100% of uncomplicated and 70% of complicated cases and there were no side effects or toxicity. In vitro studies with 120 consecutive clinical isolates of Enterobacteriaceae gave an MIC90 of 8 mg/L for Escherichia coli, although some resistant strains were found in other species.

Adult↗

The use of new beta-lactam antibiotics in urinary tract infections.

Results of treatment of urinary tract infection in 110 patients using new beta-lactam antibiotics are presented in summary. While in the uncomplicated infections a cure rate approaching 100% was observed even with very small dosages, complicated cases required higher dosages to achieve satisfactory clinical cure rates and especially to achieve acceptable bacteriological cure rates. The continuous need for new, more potent antibiotics is becoming apparent due to the increasing resistance rates of pathogens to the existing agents. The group of beta-lactam antibiotics offers much hope due to the continuous development of numerous new compounds with better antibacterial and kinetic properties, offering at the same time a very high degree of safety, compared to aminoglycosides and most other antibiotic groups.

Anti-Bacterial Agents↗

Management of surgical infections.

Results of treatment of 151 surgical infections with a variety of antimicrobial regimes were retrospectively compared. Diagnoses included diffuse peritonitis (43), severe soft tissue infections (11), septicaemia accompanying abdominal infections (29), intra-abdominal abscesses (36), local peritonitis (27) and other localized infections (5). A total of 211 anaerobic and 130 aerobic strains were isolated. A cure rate of 92% was achieved with metronidazole or ornidazole used alone and 89% with these nitroimidazoles plus an aminoglycoside. Results were equally satisfactory regardless of whether a surgical procedure, such as drainage was performed. Clindamycin and the aminoglycosides had satisfactory results in combination, but not when used alone. Good controlled trials are now justified to define the need for an aminoglycoside and/or surgery in addition to a nitroimidazole.

Abscess↗

Rifaprim in urinary tract infection: a comparison with co-trimoxazole.

Two regimes of rifaprim (RPM), a 3.75 to 1 combination of rifampicin (RIF) and trimethoprim (TMP), were compared with co-trimoxazole (CO-T) for the treatment of urinary tract infection in 60 patients. Dosages were: A, 450 mg RIF + 120 mg TMP twice daily; B, 600 mg RIF + 160 mg TMP at bedtime and C, 800 mg sulphamethoxazole (SMZ) + 160 mg TMP twice daily. Clinical results were similar but CO-T treatment was accompanied by a greater number of late bacteriological failures. In none of 40 patients receiving RPM did resistance to any of the components develop, while in three of 20 patients receiving CO-T resistance to TMP or SMZ emerged during treatment. There were no side effects in the patients receiving RPM, but three patients developed transient laboratory abnormalities. One patient receiving CO-T had a rash and one further transient laboratory abnormalities. Satisfactory concentrations of RIF and TMP were measured in urine up to 24 h after a dose of 600 mg RIF + 160 mg TMP. RIF may be a better companion to TMP than the sulphonamides for the treatment of urinary tract infection.

Adult↗

Prospective randomized comparative studies of mezlocillin/cefotaxime vs. gentamicin/cefoxitin.

In 54 patients suffering from a variety of severe systemic infections the combination of mezlocillin (4 g iv 6-hourly) plus cefotaxime (2 g iv 8-hourly) was compared to that of gentamicin (1.5 mg/kg im or iv 8-hourly) plus cefoxitin (2 g iv 6-hourly). In the gentamicin/cefoxitin group metronidazole (500 mg iv 8-hourly) was added for anaerobic infections. Treatment assignment was randomized. The patients' diagnoses were: pyelonephritis (24), pneumonia (14), infected burns (9), osteomyelitis (2), and abdominal infections (5). Pathogens included: Escherichia coli (31), other Enterobacteriaceae (21), Pseudomonas aeruginosa (13), anaerobes (4), and others (2). Treatment with mezlocillin/cefotaxime cured 20 (74%) of 27 patients and caused improvement in 5, while in 19 (70%) patients the pathogens were eradicated. In the gentamicin/cefoxitin group 17 (63%) of 27 patients were cured and 6 improved, while in 15 (56%) pathogens were eradicated. One patient in the first group developed a rash, while in the second group two patients developed thrombophlebitis and another two transient nephrotoxicity. The combination of mezlocillin and cefotaxime can be recommended for the rational and empirical treatment of serious systemic infections.

Adult↗

A study of the effectiveness of rifaprim in chronic prostatitis caused mainly by Staphylococcus aureus.

Rifampicin plus trimethoprim (rifaprim) was used to treat 20 patients with chronic prostatitis in exacerbation: 11 received 2 tablets at bedtime for 15 days followed by 1 tablet at bedtime for another 105 days, and 9 received 1 tablet in the morning and 2 tablets at bedtime for 15 days, then 2 tablets at bedtime for 15 days followed by 1 tablet at bedtime for another 90 days. All patients had an enlarged tender prostate and all but 2 were symptomatic. In 10 patients previous treatment, including co-trimoxazole in 5, had failed. Cultures of the expressed prostatic secretions yielded Staphylococcus aureus in 17 patients and gram-negative micro-organisms in 3. At the end of treatment 6 of 11 patients given the lower dosage were cured clinically and bacteriologically compared to 8 of 9 given the higher dosage. After 2 to 3 years of following 5 of 9 patients in the first group and all 7 in the second group had not suffered relapse. From our study it is evident that rifaprim is a potent drug in the treatment of chronic prostatitis caused mainly by Staphylococcus aureus. A promptness of therapeutic response and the rate of cure at the end of treatment as well as after at least 2 years of followup favor the higher drug dosage.

Adult↗

Pharmacokinetics of amikacin in infants and pre-school children.

The pharmacokinetic properties of amikacin sulfate in infants and children aged from three weeks to 6 years were studied during treatment with doses of 7.5 mg/kg every 12 hours using standard assay methods and technique of two compartment open model kinetic analysis. Peak serum concentrations of amikacin were measured 30 or 60 min after the first intramuscular injection. These ranged from 11.8 microgram/ml to 23 microgram/ml in infants and from 9.0 microgram/ml to 29 microgram/ml in children. Five minutes after the first intravenous bolous injection they varied from 16 microgram/ml to 29.8 microgram/ml in infants and from 34 microgram/ml to 42 microgram/ml in children. Twelve hours after injection serum concentrations were less than 0.8 microgram/ml in all patients. Mean serum half-lives of amikacin in infants and children were 2.1 hours and 2.0 hours after intramuscular, and 2.2 and 2.0 hours after intravenous administration respectively. No evidence of accumulation was observed after four days treatment. The amount of antibiotic recovered within 12 hours from the urine in all patients ranged from 34.5 to 65% of an intramuscular dose, and from 45.8 to 63.3% of an intravenous dose. The dosage regime of 7.5 mg/kg body weight given every 12 hours should be safe and effective for the treatment of infections in the age groups studied.

Age Factors↗

Elimination kinetics of mezlocillin in normal and impaired renal function including the effects of dialysis.

The kinetics of 6-[(R)-2-[3-methylsulfonyl-2-oxo-imidazolidine-1-carboxamido]-2-phenyl-acetamido]-penicillanic acid sodium salt (mezlocillin, Baypen) in renal failure were studied in 23 patients, given 5 g as i.v. infusion. Serum half-lives (t1/2) were around 60 min in normal renal function, 90 to 120 min in patients with a creatinine clearance (Clcr) of 30-60 ml/min, 160 to 190 min at a ClCr of 15 to 30 ml/min and 6 to 14 h in patients with a ClCr below 10 ml/min. There was a linear correlation between serum creatinine and t1/2. Peritoneal dialysis reduced t1/2 to 3 to 4 h and during haemodialysis t1/2 was 1.4 to 2 h with a mean extraction ratio of 0.25. Levels in urine were very high, even in advanced renal failure and the recovery rate was around 60% of dose in normal renal function, but less in renal failure, being only 10-20% at a ClCr of less than 10 ml/min. Levels in peritoneal dialysate fluctuated between 20 and 30 microgram/ml for 4 to 6 h after the infusion, falling slowly but still averaging 10 to 15 microgram/ml after 18 h. Dosage regimens are proposed for various situations in impaired renal function.

Half-Life↗

Cefoxitin and cephalothin: antimicrobial activity, human pharmacokinetics, and toxicology.

Cefoxitin, a semisynthetic cephamycin, has been compared with the widely used parenteral cephalosporin, cephalothin, in terms of antibacterial activity, human pharmacokinetics, and toxicity. For both compounds, minimal inhibitory concentrations were within the therapeutic range against the 156 gram-positive cocci tested (except group D streptococci), but cephalothin was 8 to 20 times more active. Regarding the 313 gram-negative organisms tested, both antibiotics were of approximately equal activity against cephalothin-susceptible strains, but cefoxitin was outstandingly superior against Providencia spp. and indole-producing Proteus spp., and markedly better against Serratia marcescens and Bacteroides fragilis. Against these organisms, cefoxitin but not cephalothin would be expected to be therapeutically valuable. Antibiotic activity levels in the serum and urine of 18 human volunteers after parenteral administration were higher and more prolonged in the case of cefoxitin, which had an average terminal serum half-life of about 45 min and a urinary recovery of about 90%. Cefoxitin was entirely nontoxic and, given intramuscularly, slightly less painful then cephalothin. These preliminary results suggest that cephamycins may prove to be a significant chemotherapeutic advance.

Adult↗

Cefoxitin, a new semi-synthetic cephamycin: an in-vitro and in-vivo comparison with cephalothin.

The activity of cefoxitin was compared with that of cephalothin against 229 bacterial strains. Cefoxitin was more active against most Gram-negative strains, notably against indole-producing Proteus spp., which are usually resistant to the cephalosporins. Cefoxitin was not susceptible to any significant extent to degradation by beta-lactamases produced by Gram-negative organisms. Against Gram-positive organisms, however, cefoxitin was considerably less active than cephalothin, but minimum inhibitory concentrations for Staphylococcus aureus were well within therapeutically attainable blood levels.Pharmacokinetic studies in 18 volunteers showed a higher and longer sustained antibiotic activity in serum and urine after injections of cefoxitin than after equal doses of cephalothin. Urinary recovery of cefoxitin activity was also much higher than that of cephalothin. No evidence of toxicity due to cefoxitin was found. Cefoxitin was slightly less painful after intramuscular injection than cephalothin.

Adolescent↗