Oral cephalosporins: clinical results in urinary tract infections.
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Biomedical subjects
Publications and source records attributed to H Giamarellou.
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In order to compare the in vitro killing activity of meropenem and imipenem against multiresistant P.aeruginosa 14 strains were used. All nosocomial isolates were susceptible to meropenem and imipenem minimum inhibitory concentration (MIC < or = 4 micrograms/ml) and resistant to at least two other antimicrobial agents of diverse chemical class with antipseudomonal activity. Forty-two killing curves were performed by exposing a 5 x 10(5) CFU/ml log-phase inoculum to 1x minimum bactericidal concentration (MBC) of each carbapenem. Meropenem was found to possess a slower killing rate than imipenem over the first 5 hours of P.aeruginosa exposure, but to be equally effective as imipenem after 24 hours of incubation. Forty percent and 11.1% of P.aeruginosa strains developed resistance to imipenem and meropenem respectively after a 24-hour exposure to carbapenem. The authors speculate about the underlying mechanisms explaining the higher rate of resistance development to imipenem than to meropenem.
The potential role of the commercially available fluoroquinolones in the treatment of Gram-positive infections is discussed on the basis of data obtained from animal experiments and clinical trials. In respiratory tract infections, and particularly in community-acquired pneumonia, it is evident that the presently available quinolones cannot be prescribed empirically as first-line therapy because of their borderline activity against Streptococcus pneumoniae and anaerobes. Reports of pneumococcal seeding in other tissues during quinolone therapy render their administration a debatable issue. Experience in endocarditis is limited to the use of ciprofloxacin plus rifampicin in intravenous drug users with right-sided Staphylococcus aureus endocarditis. Patients with staphylococcal osteomyelitis are included among cases of other bone infections. In noncontrolled studies ciprofloxacin, ofloxacin and pefloxacin attained a staphylococcal eradication rate ranging from 70 to 100%, while the addition of rifampicin has been proven to reduce the emergence of resistant mutants during therapy. In soft tissue and skin structure infections that also involve Gram-negative bacteria, ciprofloxacin and ofloxacin eradicated 72.6 and 89% of staphylococci, respectively; however, the presence of diabetes or vascular disease compromised the success of treatment. In staphylococcal peritonitis complicating continuous ambulatory peritoneal dialysis, results with ciprofloxacin given intravenously or intraperitoneally were promising. In infections in neutropenic hosts, success of prophylaxis or therapy is still not clear, since colonisation and breakthrough bacteraemias with viridans streptococci and staphylococci have been reported. Furthermore, therapeutic results are compromised by the low response rate in Gram-positive infections. Despite the reported clinical efficacy of the newer fluoroquinolones, physicians should be alerted to the emergence of staphylococci resistant to fluoroquinolones, mainly methicillin-resistant variants.
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A multicentre, non-comparative study evaluated the efficacy and safety of the new aminoglycoside isepamicin in hospitalised patients with various infections. Isepamicin was administered once daily with the daily dosage stratified according to the severity of infection: 15 mg/kg isepamicin for severe potentially systemic infections (53 patients) or 8 mg/kg isepamicin for less severe and localised infections (56 patients). The largest groups of patients had urinary tract infection (n = 54) or lower respiratory tract infection (n = 31); smaller numbers of patients were enrolled with skin and soft tissue infections (n = 9), intra-abdominal infections (n = 8) or obstetric and gynaecological infections (n = 7). In the patients receiving 15 mg/kg isepamicin, clinical cure or improvement occurred in 19/21 patients with lower respiratory tract infections, 8/13 patients with urinary tract infections, 6/6 patients with skin infections, 5/6 patients with intra-abdominal infections and 6/7 patients with obstetric gynaecological infections. In the patients receiving 8 mg/kg isepamicin, 40 out of 41 patients with urinary tract infections were considered cured or improved as were 8/10 patients with lower respiratory tract infections, 1/3 patients with skin infections and 1/2 patients with intra-abdominal infections. Nine per cent of patients reported at least on adverse event during the study. Two patients (one from each dosage group) discontinued treatment because of adverse events, respiratory disorder and erythematous rash, but neither event was considered to be severe of life threatening No patients had evidence of ototoxicity by pure-tone audiometry and no patients had potentially significant increases in serum creatinine which were considered to be treatment related. The results of this study indicate that treatment with isepamicin once daily is effective and well tolerated in hospitalised adults with various infections.
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Since 1984, when the first fluoroquinolone, norfloxacin, was marketed in Europe, there has been a marked increase in the usage of this class of drugs. In order to evaluate the influence of this drug usage on the prevalence of resistance to fluoroquinolones in clinical isolates of the family Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus, coagulase-negative staphylococci and Enterococcus faecalis we reviewed the susceptibility data from four collaborative surveys conducted between 1983 and 1990 by the Study Group 'Bacterial Resistance' of the Paul-Ehrlich-Society for Chemotherapy. All participating laboratories used the same standardized methods. Minimal inhibitory concentrations were determined by the broth microdilution method. More than 20,000 bacterial strains were tested. The results are presented for ciprofloxacin, which is regarded as the representative of the fluoroquinolones. Using > or = 4 mg/l as a breakpoint for resistance to ciprofloxacin, the prevalence of resistant strains of the family Enterobacteriaceae in Central Europe between 1983 and 1990 remained below 1%. In contrast, the resistance rates in P. aeruginosa were 0.7%, 1.0%, 3.8% and 7.0%, in S. aureus 0%, 0.5%, 6.6% and 6.8%, and in E. faecalis 2.2%, 0.7%, 4.9% and 7.7% in 1983, 1986, 1989 and 1990, respectively. The latest study carried out in cooperation with 78 laboratories from 12 European countries revealed great differences in the prevalence of resistance to fluoroquinolones from one species to another ranging from 0% with Proteus vulgaris and Salmonella spp. to 26.7% with Providencia stuartii.(ABSTRACT TRUNCATED AT 250 WORDS)
Polyunsaturated fatty acids (PUFAs) constitute an ingredient of the daily diet and therefore they might be in close contact with the polymicrobial gastrointestinal flora. In order to study the interaction of bacteria and PUFAs, eight Escherichia coli strains were cultured in the presence of docosahexaenoic acid (DHA) at a concentration of 100 micrograms/ml, and six of the latter eight at 75 micrograms/ml whereas nine other E. coli strains were cultured in the presence of 50 micrograms/ml gamma-linolenic acid (GLA). DHA provoked > or = 4-fold increases in the minimum inhibitory and bactericidal concentrations of various antibiotics in six strains at 100 micrograms/ml and in three strains at 75 micrograms/ml, which were not antibiotic-specific and involved mainly aminoglycosides. GLA provoked in four strains > or = 4-fold increases in MICs-MBCs of ampicillin. The clinical relevance of these observations require further study.
The in vitro activity of FCE 22101 against 97 Gram-negative aerobic nosocomial isolates was compared with that of ceftriaxone using the agar dilution method. Thirty-four (79%) of the 43 ceftriaxone resistant (MIC > 16 mg/l) isolates were found to be FCE 22101 susceptible (MIC < or = 8 mg/l), while of the ceftriaxone susceptible isolates, only seven Enterobacter cloacae and one Serratia spp strain were FCE 22101 resistant. The new penem may offer an alternative for treating nosocomial infections due to aerobic Gram-negative strains resistant to third generation cephalosporins, provided that clinical studies confirm its clinical usefulness.
Periareolar nonpuerperal breast infection is a troublesome entity whose treatment is still a matter of debate. Thirty-eight female patients--9 with acute infection and 29 with chronic infection--were prospectively studied over a 3-year period. Sixty isolates were harvested from 50 pus specimens obtained by fine-needle aspiration, with a predominance of staphylococci (23 isolates) and peptostreptococci (18 isolates). On the basis of these findings, an antimicrobial regimen consisting most often of amoxicillin plus clavulanic acid was administered for 6-8 weeks. Simultaneous surgery was required in 13 cases (34.2%). Despite a good response during therapy, 7 (21.9%) of 32 patients relapsed during a follow-up period of < or = 3 years; all 7 patients had presented with chronic infection. We conclude that prolonged therapy with agents active against both staphylococci and anaerobes is essential in periareolar breast infection; in cases with an established fistula, radical surgery (i.e., fistulotomy or fistulectomy) appears inevitable.
The distribution of aac(6')-I genes in 62 strains of Acinetobacter spp. resistant to amikacin, netilmicin, and tobramycin and susceptible to gentamicin, a phenotype compatible with synthesis of an AAC(6')-I enzyme, was studied by PCR and by DNA hybridization. Both methods gave similar results. Among the 51 Acinetobacter baumannii strains, aac(6')-Ib was found in 19 isolates and aac(6')-Ih was found in the remaining strains. The aac(6')-Ig gene was present in all 10 A. haemolyticus strains studied and was detected only in this species. A pair of degenerate oligonucleotides complementary to conserved regions of aac(6')-Ic, -Id, -If, -Ig, and -Ih enabled detection of these genes and also of aac(6')-Ij, recently recognized in Acinetobacter sp. strain 13.
Eighty-five patients undergoing cataract surgery were given for prophylaxis of intraocular infection two intravenous doses each of 200 mg, 300 mg or 400 mg ciprofloxacin (35 patients), 400 mg or 800 mg pefloxacin (30 patients), or 400 mg ofloxacin (20 patients). Ciprofloxacin levels in aqueous humour ranged from 0.02 to 0.50 microgram/ml, pefloxacin levels from 1.04 to 7.80 micrograms/ml, and ofloxacin levels from 0.44 to 2.27 micrograms/ml with ratios of aqueous humour to serum levels ranging from 3.8% to 25%, 21% to 48.1% and 44% to 88.4%, respectively. It is concluded that the quinolones studied might be suitable for surgical prophylaxis or treatment of anterior chamber infections due to Enterobacteriaceae, while ciprofloxacin at high doses is preferable for Pseudomonas aeruginosa infections.
In a prospective randomized study meropenem was compared with imipenem/cilastatin in the treatment of 62 patients with intraabdominal infections requiring surgery. The patients were suffering from diffuse or local peritonitis of moderate severity complicating in most cases gangrenous appendicitis, stomach perforation or gallbladder disease. There were 30 patients in the meropenem group and 32 patients in the imipenem/cilastatin group. Both antibiotic regimens were given intravenously at a dosage of 1 g every 8 h for a mean duration of 7.7 days in the meropenem group versus 8.6 days in the imipenem/cilastatin group. Fifty-nine aerobic strains and 15 anaerobic strains were isolated from cultures of pus taken intraoperatively, the meropenem MICs ranging from < or = 0.25 to 2 micrograms/ml. At follow-up at least one month after treatment the outcome was considered successful in all of 27 evaluable patients given meropenem and in all of 29 evaluable patients given imipenem/cilastatin. Both antibiotic regimens were well tolerated.
Since infection develops in significant numbers of hospitalized patients, the problem of resistance to third-generation cephalosporins is of increasing concern. We evaluated the efficacy of cefepime 1 g bd as treatment for acute, moderately severe bacterial infection in 239 hospitalized patients (mean age 60 years). Of these patients, 204 were evaluated clinically for urinary tract infection (UTI) (n = 90), lower respiratory tract infection (LRTI) (n = 70), skin and soft tissue infection (S/STI) (n = 12) and bacteraemia which was associated with either UTI or LRTI (n = 32) but not included in the previously mentioned UTI and LRTI groups. Amongst the pathogens isolated (36 Gram-positive, 150 Gram-negative), the most predominant species were Escherichia coli in UTI and bacteraemia (n = 81), Streptococcus pneumoniae in LRTI and bacteraemia (n = 23), Haemophilus influenzae in LRTI (n = 16), Pseudomonas aeruginosa (n = 4) and Enterobacter cloacae (n = 2) in S/STI. The mean duration of treatment was 8.5 days and was the same for the 204 clinically evaluable patients. Overall, the clinical cure rate for cefepime was 94% (191/204). Pathogen eradication was achieved in 93% (185/199) of infections. Of the patients with associated bacteraemia, the clinical cure rate was 97% (31/32) and 94% (16/17) of the pathogens were eradicated. Cefepime therapy was well-tolerated. Treatment was discontinued in eight patients (3%) because of local intolerance and in five patients (2%) because of drug-related adverse events (rash, headache and pruritus). Cefepime 1 g bd is as safe and effective as other parenteral cephalosporins for the treatment of acute bacterial UTI, LRTI and S/STI, including those cases with associated bacteraemia. The bd dosing schedule and reported lack of cross-resistance with other cephalosporins against some species of aerobic Gram-negative bacilli make cefepime an attractive treatment option in hospitalized patients.
The in vivo efficacies of ceftazidime, aztreonam, and the combinations of ceftazidime with amikacin and aztreonam with amikacin were studied in the rabbit left-sided endocarditis model by using two strains of Pseudomonas aeruginosa, one multisusceptible and one multiresistant, in a total of 156 animals. Antibiotics were given intramuscularly for 10 days, as follows: amikacin, 7 mg/kg of body weight every 8 h, and ceftazidime and aztreonam, 50 mg/kg every 8 h. All regimens except amikacin alone significantly reduced the number of CFU per gram of vegetation (P < or = 0.008), but only for the multisusceptible strain for which sterile vegetations were obtained in 20, 25, 21, 75, and 53% of the groups treated with amikacin, ceftazidime, aztreonam, and the combination groups ceftazidime-amikacin and aztreonam-amikacin, respectively (ceftazidime plus amikacin versus controls, P = 0.001). Regarding the decrease in the numbers of colonies in vegetations, (i) all regimens significantly reduced the number of CFU per gram of vegetation (P < 0.001), (ii) results with ceftazidime-amikacin compared with those with monotherapy were significantly different (P < or = 0.007), and (iii) results with aztreonam-amikacin, although better than those with monotherapy, were marginally not statistically significant. At 1 h postdose, mean amikacin, aztreonam, and ceftazidime levels in serum were 35 +/- 19.4, 89.6 +/- 8.16, and 92.61 +/- 11.52 micrograms/ml, respectively. It was concluded that the combination of ceftazidime, and possibly aztreonam, with amikacin given at high doses and short intervals could have a place in the therapy of patients with left-sided endocarditis caused by P. aeruginosa.
The ability of oral pefloxacin to penetrate into maxillary sinus cavity and nasal secretions was studied in 39 patients suffering from an exacerbation of chronic maxillary sinusitis. The mean levels of pefloxacin in sinus aspirate fluid 0, 3, 6, 9 and 12 h after the second oral dose of 400 mg were 2.30, 6.92, 3.74, 3.47 and 2.82 mg/l respectively. In sinus cystic fluid (macroscopically non-purulent) the mean pefloxacin levels were 2.30, 7.15, 4.20 and 4.15 mg/l respectively, and in nasal secretion 1.90, 9.05, 3.71, 3.20 and 2.85 mg/l respectively. The mean pefloxacin levels in serum obtained simultaneously were 1.50, 5.00, 3.10, 2.70 and 2.20 mg/l respectively. It is concluded that pefloxacin accumulates in inflamed sinus fluid at concentrations exceeding blood levels.