Resistance to HIV protease inhibitors

OBJECTIVES: The efficacy and safety of levofloxacin and lomefloxacin in complicated urinary tract infections (UTIs) were compared in a randomized, open-label, multicenter study. METHODS: Outpatients were randomized to receive levofloxacin (250 mg once daily) for 7 to 10 days or lomefloxacin (400 mg once daily) for 14 days. Three hundred thirty-six patients (171 with levofloxacin, 165 with lomefloxacin) were evaluable for microbiologic efficacy, and 461 patients (232 with levofloxacin, 229 with lomefloxacin) for safety. RESULTS: The overall microbiologic eradication rate of pathogens was 95.5% (168 of 176) for levofloxacin and 91.7% (154 of 168) for lomefloxacin. Eradication rates with respect to patients were 95.3% (163 of 171) and 92.1% (152 of 165) for levofloxacin and lomefloxacin, respectively. At the 5 to 9-day post-therapy visit, symptoms were completely resolved in 84.8% of levofloxacin-treated patients and were decreased in 8.2% (93.0% clinical success). Among the lomefloxacin-treated patients, complete resolution was seen in 82.4%, with decreased symptoms in 6.1% (88.5% clinical success). Drug-related adverse events (AEs) were reported by 10 (2.6%) and 18 (5.2%) levofloxacin- and lomefloxacin-treated patients, respectively. Compared with levofloxacin-treated patients, more lomefloxacin-treated patients experienced photosensitivity reactions (3 [1.3%] versus 0) and dizziness (2 [0.9%] versus 0). Nausea (3 [1.3%] versus 1 [0.4%]) was more frequent in the levofloxacin-treated group. Six patients in each treatment group had a gastrointestinal AE (1.7%); rash was reported more frequently with lomefloxacin (4 patients [0.4%]) than with levofloxacin (1 patient [0.4%]). Discontinuation because of AEs was observed in 8 (3.4%) levofloxacin- and 14 (6.1%) lomefloxacin-treated patients. CONCLUSIONS: Once-daily levofloxacin is as effective as and has a superior tolerability profile than lomefloxacin in the treatment of complicated UTIs.     

Transcription factor GATA-1 and erythroid development

A double-blind trial was conducted in 385 patients with suspected bacterial intra-abdominal infections to compare the efficacy and safety of ampicillin-sulbactam with cefoxitin. Patients were randomized to receive either 3 g ampicillin-sulbactam (2 g ampicillin-1 g sulbactam), or 2 g cefoxitin, every 6 hours. To be evaluable, patients had to demonstrate positive culture evidence of peritoneal infection at the time of operation. A total of 197 patients were evaluable for clinical efficacy. The two treatment groups were comparable in demographic features and in the presence of risk factors for infection. Clinical success (absence of infection and of adverse drug reaction) was observed in 86% of patients in the ampicillin-sulbactam group and 78% in the cefoxitin group. Eradication of infection occurred in 88% of the ampicillin-sulbactam group and 79% of the cefoxitin group. There were no differences in the nature or frequency of side effects observed in the two groups. Ampicillin-sulbactam demonstrated no difference in safety or efficacy when compared with cefoxitin in the treatment of serious intra-abdominal infections of bacterial origin.     

Empiric treatment of hospital-acquired lower respiratory tract infections with meropenem or ceftazidime with tobramycin: a randomized study. Meropenem Lower Respiratory Infection Group

OBJECTIVE: To evaluate the efficacy and tolerability of intravenous empiric treatment with meropenem compared with ceftazidime-tobramycin in patients with hospital-acquired lower respiratory tract infections. DESIGN: Prospective, nonblind, randomized trial. SETTING: Multicenter trial conducted at 22 centers. PATIENTS: Two hundred eleven patients were enrolled and 121 were evaluable for the analysis of both clinical and bacteriologic efficacy. INTERVENTIONS: One hundred four patients were randomized to receive intravenous meropenem (1000 mg) every 8 hrs and 107 patients were randomized to receive intravenous ceftazidime (2000 mg) plus tobramycin (1 mg/kg) every 8 hrs. Sixty-three meropenem-treated patients and 58 ceftazidime-tobramycin-treated patients were eligible for the analysis of clinical and bacteriologic efficacy. In the ceftazidime-tobramycin group, 32 (55%) evaluable patients received more than six doses of tobramycin, 24 (41%) received six doses or fewer, and two (3%) did not receive any tobramycin. MEASUREMENTS AND MAIN RESULTS: The analysis of efficacy was based on the clinical and bacteriologic responses at the end of treatment. Satisfactory clinical responses occurred in 56 (89%) of 63 of the meropenem-treated patients and in 42 (72%) of 58 of the ceftazidime-tobramycin-treated patients (p = .04). Corresponding bacteriologic response rates were 89% and 67%, respectively (p = .006). The frequency and profile of drug-related adverse events was similar across treatment groups. Seizures were reported in three meropenem-treated patients, but these seizures were considered by the investigator to be unrelated to treatment. CONCLUSIONS: Meropenem is well tolerated and more efficacious than the combination of ceftazidime and tobramycin for the initial empiric treatment of hospital-acquired bacterial pneumonia.     

Bronchial mucoid impaction due to the monokaryotic mycelium of Schizophyllum commune

PURPOSE: A prospective trial was done to test the efficacy of antimicrobial prophylaxis in patients undergoing transurethral surgery. MATERIALS AND METHODS: A total of 75 adults with preoperatively sterile urine was randomized to receive either 400 mg. oral fleroxacin once daily or placebo as long as the catheter was in place. Urine cultures were obtained preoperatively and after removal of the catheter just before hospital discharge. Growth of 10(4)/ml. or more bacteria was considered a positive urine culture. RESULTS: Postoperative urinary tract infection rates were significantly lower in the fleroxacin group (3%) than in the placebo group (23%). Our study demonstrated the benefit of antimicrobial prophylaxis in preventing urinary tract infection after transurethral surgery, including resection of the prostate, in patients with sterile urine. CONCLUSIONS: The oral administration of 1 daily tablet of fleroxacin for the duration of catheterization is a safe, efficacious and clinically feasible regimen.     

Clinical studies on vancomycin in the treatment of MRSA infection

We evaluated the effectiveness and safety of vancomycin (VCM) alone and in combination with beta-lactam antibiotics in the treatment of MRSA infections, and obtained the following results: 1. Effectiveness. (1) In cases of MRSA infections alone, the improvement rate was 71.4% (5/7 patients) with VCM alone and 77.8% (35/45) with VCM in combination with beta-lactam antibiotics. (2) In cases of polymicrobial infections, few cases were treated with VCM alone, but the improvement rate in combination use with beta-lactam antibiotics was 71.8% (28/39). 2. Bacteriological effect. (1) In cases of single infection with MRSA, the rate of bacterial eradication was 71.4% (5/7) with VCM alone and 68.2% (30/44) with VCM in combination with beta-lactam antibiotics. (2) In cases of polymicrobial infections, few cases were treated with VCM alone, but the rate of bacterial eradication in combination use with be ta-lactam antibiotics was 63.2% (24/38) against MRSA and 31.6% (12/38) against polymicrobial agents including MRSA. 3. Safety. Occurrences of adverse reactions and abnormal laboratory test values when VCM was used alone or when it is used in combination with another drug were about the same in these uses. As a whole, advance reactions were observed in 16 patients (9.5%). Main adverse reactions were whole body redness, drug eruption, and rash etc. Abnormal laboratory test values were observed mainly in hepatic functions, and renal functions. 4. VCM concentrations in blood was determined in 38 patients. Doses of 0.5 g and 1.0 g of VCM was administered by intravenous drip infusion over a period of 1 to 2 hours, and mean blood concentrations 1 to 2 hours after the completion of drip infusion were 25.4 micrograms/ml and 14.4 micrograms/ml, respectively. 5. Synergic effects between VCM and other antibiotics tested were observed in FIC index against all of the six MRSA strains isolated from six patients, and the clinical effects of improvement or better were obtained against five of them.     

Efficacy and tolerability of brodimoprim od versus norfloxacin bid in the treatment of bacterial urinary tract infections

The efficacy and tolerability of brodimoprim OD versus norfloxacin BID were studied in patients affected by bacterial urinary tract infections. The study was performed in 203 patients divided into two parallel randomized groups orally given either brodimoprim 400 mg OD on the first day followed by 200 mg OD for 2 days, or norfloxacin 400 mg BID respectively. The efficacy of treatment was evaluated by the bacterial cultures, tolerability, analysis of signs and symptoms, a complete physical examination and from laboratory data. The results showed that brodimoprim and norfloxacin in the majority of patients resulted in a reduction of fever and symptoms caused by the infective process. Of the 103 patients enrolled in the brodimoprim OD group, 99 had a complete course of therapy with a positive outcome. There was only one case of failed treatment and 3 cases which could not be evaluated because of voluntary interruption of treatment. Of the 100 patients treated with norfloxacin BID, 94 completed therapy with a positive clinical outcome and there were 4 cases of treatment failure. Thus the efficacy of brodimoprim OD appears comparable to that of norfloxacin BID in the treatment of urinary tract infections.     

Enhanced chemiluminescence response of polymorphonuclear leukocytes by new quinolone antimicrobials

Some of the many antimicrobial agents (beta-lactams, macrolides, aminoglycosides, tetracyclines, new quinolones; NQs) were reported to have a bactericidal or bacteriostatic effect cooperating with host defense mechanisms including polymorphonuclear neutrophils (PMNs). We investigated the effect of new quinolone antimicrobials on chemiluminescence (CL) response of human PMNs. Among many NQs, we chose ofloxacin, lomefloxacin, fleroxacin, sparfloxacin, AM-1155, NM-394, Q-35, Y-26611 and T-3761. Twenty-five or 100 micrograms/ml of fleroxacin and ofloxacin enhanced luminol-dependent CL response of PMNs up to 1.5-2.0 times compared to the drug free condition. Other antimicrobial agents, however, inhibited CL response. This suggested that fleroxacin and ofloxacin were more efficient in the treatment of bacterial infections with respect to the interaction between antimicrobials and PMNs.     

Panic response to sodium lactate infusion in patients with multiple chemical sensitivity syndrome

In this double-blind study, 557 patients with lower respiratory tract infection were randomly assigned to receive amoxicillin/clavulanate orally either every 12 hours (875/125 mg) or every 8 hours (500/125 mg) for 7-15 days. For the 455 patients evaluable for clinical efficacy at the end of therapy, clinical success was similar in the two groups: 93% and 94% in the 12-hour and 8-hour groups, respectively (P = .42). Bacteriologic success at the end of therapy was also comparable: 97% and 91% in the 12-hour and 8-hour groups, respectively (P = .86). The occurrence of adverse events related to treatment was similar for the two groups, but fewer patients in the 12-hour group reported moderate or severe diarrhea. Amoxicillin/clavulanate (875/125 mg) given every 12 hours is as effective and safe as every-8-hours administration of the combination (500/125 mg) for the treatment of lower respiratory tract infection.     

Activity of fleroxacin alone and in combination with clindamycin or metronidazole in experimental intra-abdominal abscesses

To assess the potential efficacy of fleroxacin in combination with clindamycin or metronidazole in mixed aerobic and anaerobic infections, we used a rat model of intra-abdominal abscesses in which the inoculum consisted of pooled rat feces mixed with BaSO4. Two hours after bacterial challenge, antimicrobial therapy was begun intravenously with regimens designed to stimulate human pharmacokinetics. A combination of clindamycin and gentamicin was included as an established treatment regimen. After 8.5 days of therapy, final bacterial counts in abscesses showed that fleroxacin alone or combined with metronidazole or clindamycin effectively eradicated Escherichia coli, with bacterial densities of < or = 2.84 +/- 0.1, < or = 2.9 +/- 0.1, and < or = 2.9 +/- 0.1 (mean +/- standard error of the mean) log10 CFU/g, respectively. The addition of either clindamycin or metronidazole to fleroxacin substantially enhanced the effectiveness of the regimens against Bacteroides fragilis, with bacterial counts of < or = 3.0 +/- 0.1 or < or = 2.9 +/- 0.1 log10 CFU/g, respectively, versus 9.2 +/- 0.2 log10 CFU/g for fleroxacin alone. The combination of metronidazole and fleroxacin also resulted in a significantly greater reduction of peptostreptococci and Bacteroides thetaiotaomicron than fleroxacin alone (< or = 2.9 +/- 0.1 versus 6.1 +/- 0.9 log10 CFU/g and 3.3 +/- 0.4 versus 8.3 +/- 0.1 log10 CFU/g, respectively). Except for those of B. fragilis, counts of other anaerobes were reduced to a greater extent by metronidazole plus fleroxacin than by clindamycin plus fleroxacin, although differences were not always significant. Metronidazole plus fleroxacin was at least as active a clindamycin plus gentamicin against all species and was significantly more active against Clostridium spp. No regimen effectively eradicated enterococci from the abscesses. These results suggest that the addition of either metronidazole or clindamycin would effectively enhance the spectrum of fleroxacin for treatment of mixed aerobic and anaerobic infections.     

Use of ampicillin/sulbactam versus imipenem/cilastatin in the treatment of limb-threatening foot infections in diabetic patients

In a double-blind randomized trial, imipenem/cilastatin (I/C; 500 mg every 6 hours) and ampicillin/sulbactam (A/S; 3 g every 6 hours) were compared in regard to their efficacy for initial empirical and definitive parenteral treatment of limb-threatening pedal infection in diabetic patients. The major endpoints of treatment were cure (resolution of soft-tissue infection), failure (inadequate improvement, necessitating a change in antibiotic therapy), and eradication (clearance of all pathogens from the wound and any bone cultures). Patients in the two treatment groups were similar in regard to the severity of diabetes; presence of neuropathy and peripheral vascular disease; site and severity of infection; pathogen isolated; and frequency of osteomyelitis (associated with 68% of the 48 A/S-treated infections and 56% of the 48 I/C-treated infections). After 5 days of empirical treatment, improvement was noted in 94% of the A/S and 98% of the I/C recipients. At the end of definitive treatment (days' duration [mean +/- SD]: 13 +/- 6.5 [A/S], 14.8 +/- 8.6 [I/C]), outcomes were similar: cure, 81% (A/S) vs. 85% (I/C); failure, 17% (A/S) vs. 13% (I/C); and eradication, 67% (A/S) vs. 75% (I/C). Treatment failures were associated with the presence of antibiotic-resistant pathogens and possible nosocomial acquisition of infections. The number of adverse events among patients in the two treatment groups was similar: 7 in the A/S group (4 had diarrhea and 3 had rash) and 9 in the I/C group (5 had diarrhea, 2 had severe nausea, 1 had rash, and 1 had seizure). Efficacy of A/S and I/C is similar for initial empirical and definitive treatment of limb-threatening pedal infection in patients with diabetes.     

Doxycycline is a cost-effective therapy for hospitalized patients with community-acquired pneumonia

BACKGROUND: Doxycycline has a high degree of activity against many common respiratory pathogens and has been used in the outpatient management of lower respiratory tract infections, including pneumonia. OBJECTIVE: To evaluate the efficacy of intravenous doxycycline as empirical treatment in hospitalized patients with mild to moderately severe community-acquired pneumonia. PATIENTS AND METHODS: We conducted a randomized prospective trial to compare the efficacy of intravenous doxycycline with other routinely used antibiotic regimens in 87 patients admitted with the diagnosis of community-acquired pneumonia. Forty-three patients were randomized to receive 100 mg of doxycycline intravenously every 12 hours while 44 patients received other antibiotic(s) (control group). The 2 patient groups were comparable in their clinical and laboratory profiles. RESULTS: The mean+/-SD interval between starting an antibiotic and the clinical response was 2.21+/-2.61 days in the doxycycline group compared with 3.84+/-6.39 days in the control group (P = .001). The mean+/-SD length of hospitalization was 4.14+/-3.08 days in the doxycycline group compared with 6.14+/-6.65 days in the control group (P = .04). The median cost of hospitalization was $5126 in the doxycycline group compared with $6528 in the control group (P = .04). The median cost of antibiotic therapy in the doxycycline-treated patients ($33) was significantly lower than in the control group ($170.90) (P<.001). Doxycycline was as efficacious as the other regimens chosen for the treatment of community-acquired pneumonia. CONCLUSION: Doxycycline is an effective and inexpensive therapy for the empirical treatment of hospitalized patients with mild to moderately severe community-acquired pneumonia.     

Prevention of nausea and vomiting with granisetron, droperidol and metoclopramide during and after spinal anaesthesia for caesarean section: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: To compare the safety and efficacy of a combination of amoxicillin and clavulanate potassium given orally every 12 hours (amoxicillin, 875 mg; clavulanate, 125 mg) with that given every 8 hours (amoxicillin, 500 mg; clavulanate, 125 mg) for the treatment of patients with acute bacterial maxillary sinusitis. DESIGN: Multicenter double-blind randomized double-dummy controlled trial. SETTING: Physicians' offices and ambulatory care clinics. PATIENTS: One hundred seventy patients at least 18 years of age with acute bacterial maxillary sinusitis who could be treated with an oral antimicrobial agent were randomized, and data from 134 were suitable for evaluation. Four patients were withdrawn from this study because of adverse effects. INTERVENTIONS: Patients received a combination of amoxicillin and clavulanate orally every 12 hours (amoxicillin, 875 mg; clavulanate, 125 mg) or every 8 hours (amoxicillin, 500 mg; clavulanate, 125 mg) for 14 days. MAIN OUTCOME MEASURE: Clinical success at the end of therapy. RESULTS: Clinical success at the end of therapy was similar for the 2 treatment groups, 93% and 88% of patients in the every 12-hour and every 8-hour groups, respectively (P = .76; 95% confidence interval, -4.0% to 15.6%). Clinical success rates at follow-up 2 to 4 weeks after the end of therapy were also similar in the 2 groups. Adverse events related to treatment were reported with similar frequency in the 2 groups. CONCLUSION: Amoxicillin and clavulanate given every 12 hours is as effective and as safe as administration every 8 hours for the treatment of acute bacterial maxillary sinusitis.     

Efficacy and tolerability of brodimoprim in pediatric infections

Brodimoprim is a long acting broad spectrum antibacterial agent. It is a new selective inhibitor of bacterial dihydrofolate reductase, structurally related to trimethoprim. The aim of the present study was to investigate the efficacy and tolerability of brodimoprim (10 mg/kg on the first day, 5 mg/kg/die onward) in the treatment of upper respiratory tract infections in children (age range: 2-14 years). This open group comparative study was performed either in 68 children affected by bacterial pharyngotonsillitis (37 treated with brodimoprim, 31 with erythromycin 560 mg/kg/8 hours) or in 50 patients affected by otitis media (25 treated with brodimoprim, 25 with amoxicillin/clavulanic acid 50 mg/kg/12 hours) or in 52 patients affected by acute sinusitis (25 treated with brodimoprim, 27 with amoxicillin/clavulanic acid 50 mg/kg/12 hours). All patients were clinically evaluated before admission, during the trial and 48 hours after the last dose of antibiotic. At the same time blood and secretion samples were collected for hematology/biochemistry and microbiological assays. A total of 170 subjects were treated and 141 patients demonstrated a clinical recovery/improvement following the treatment period, with approximately the same recovery rate (83%) among the groups. The bacteriological response was evaluated in 169 subjects. Eradication of pathogens was documented in 27 subjects treated with brodimoprim and 28 with erythromycin in the pharyngotonsillitis group, in 22 subjects treated with brodimoprim and 16 with amoxicillin/clavulanic acid in the otitis group and in 17 subjects treated with brodimoprim and 20 with amoxicillin/clavulanic acid in the sinusitis group. The overall eradication in brodimoprim treated patients was 77% in comparison with 76% of eradication obtained in the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multicenter, randomized study comparing levofloxacin and ciprofloxacin for uncomplicated skin and skin structure infections

BACKGROUND: The fluoroquinolone, levofloxacin, is active against most common pathogens in skin and skin structure infections. METHODS: The efficacy, tolerability, and safety of levofloxacin and ciprofloxacin were compared in a randomized, open-label, multicenter trial of patients with uncomplicated skin and skin structure infections. Of 469 patients treated, 231 received levofloxacin (500 mg qd) and 238 were given ciprofloxacin (500 mg bid). RESULTS: Overall clinical success rates (cured plus improved) for levofloxacin and ciprofloxacin were 98% and 94%, respectively (95% confidence interval [CI], -7.7, 0.7). Overall microbiologic eradication rates by patient were 98% in the levofloxacin group and 89% in the ciprofloxacin group (95% CI, -14.5, -2.7), whereas eradication rates by pathogen were 98% and 90%, respectively (95% CI, -12.6, -3.7). The eradication rate for Staphylococcus aureus was 100% in the levofloxacin group and 87% in the ciprofloxacin group (95% CI, -20.2, -5.1). Treatment-emergent adverse events were comparable, with drug-related adverse events reported in 6% of levofloxacin patients and 5% of ciprofloxacin patients. CONCLUSIONS: Levofloxacin is as effective and safe as ciprofloxacin in the treatment of uncomplicated skin and skin structure infections.     

Mutation analyses of KRAS exon 1 comparing three different techniques: temporal temperature gradient electrophoresis, constant denaturant capillary electrophoresis and allele specific polymerase chain reaction

Pefloxacin plus metronidazole versus netilmicin plus metronidazole in the prevention of nosocomial infections during contaminated surgery. Surgical prophylaxis is widely used in contaminated surgery, especially colorectal surgery. In this clinical trial the efficacy of pefloxacin 800 mg i.v. slow infusion associated to metronidazole 500 mg i.v. 1-2 hours before surgery and then metronidazole alone after 6 and 12 hours versus netilmicin 200 mg i.m. associated to metronidazole 500 mg i.v. 1-2 hours before surgery and then both after 6 and 12 hours were evaluated in 97 patients suffering by colorectal surgery. Efficacy of prophylaxis in patients was evaluated in terms of appearance of post-surgical infections (abdominal, urinary, respiratory and wound infections). In pefloxacin + metronidazole group (53 patients), two cases of wound infections (3.8%) and three cases of respiratory infections (5.8%) were observed. In netilmicin + metronidazole group (44 patients), two cases of wound infections (4.9%), three cases of urinary infections (7%), three cases of respiratory infections (7.5%) and one case of intra-abdominal infection were observed. Our data confirmed that in colorectal surgery, the association pefloxacin, drug with microbiological and pharmacokinetics characteristics suitable for prophylaxis + metronidazole, active against anaerobes pathogens, prevents post-surgical infections as well as a reference association (netilmicin + metronidazole), with the advantage of a single administration.     

A randomized, double-blind clinical trial comparing cefepime plus metronidazole with imipenem-cilastatin in the treatment of complicated intra-abdominal infections. Cefepime Intra-abdominal Infection Study Group

OBJECTIVE: To evaluate the safety and efficacy of cefepime hydrochloride plus metronidazole vs the combination of imipenem and cilastatin sodium in the treatment of complicated intra-abdominal infections in adult patients. DESIGN: Prospective, randomized, double-blind multicenter study. SETTING: University-affiliated hospitals in the United States and Canada. PATIENTS: Three hundred twenty-three patients with complicated intra-abdominal infections in whom an operative procedure or percutaneous drainage was required for diagnosis and management. INTERVENTION: Cefepime, 2 g, was administered intravenously every 12 hours (n= 164) in addition to metronidazole, 500 mg (or 7.5 mg/kg) intravenously every 6 hours. Imipenen-cilastatin sodium, 500 mg, was administered intravenously every 6 hours (n= 159). Surgical infection management was determined by the patients' surgeons. MAIN OUTCOME ASSESSMENTS: Clinical cure, defined as elimination of all signs and symptoms relevant to the original infection; and treatment failure, defined as persistence, increase or worsening of signs and symptoms resulting in an antibiotic change, requirement of an additional surgical procedure to cure the infection, or a wound infection with fever. RESULTS: Of the initial isolates, 84% were susceptible to cefepime and 92% were susceptible to imipenem-cilastatin. Among the 217 protocol-valid patients, those treated with cefepime+metronidizole were deemed clinical cures (88%) more frequently than were imipenem-cilastatin-treated patients (76%) (P=.02). Using multivariate analysis to adjust for identified clinical risk factors for an adverse outcome (severity of presenting illness, isolation of enterococcus, type of infection, and duration of prestudy hospitalization), there was a trend (P=.06) toward a higher cure rate favoring cefepime+metronidazole. Pathogens were eradicated in significantly (P=.01) more patients treated with combined cefepime and metronidazole (89%) than with imipenem-cilastatin (76%). CONCLUSION: The combination of cefepime plus metronidazole is safe and effective therapy for patients with severe intra-abdominal infections.     

A single-blind, randomised, comparative study of clarithromycin and amoxycillin suspensions in the treatment of children with lower respiratory tract infections

One hundred and forty-five children with signs and symptoms of lower respiratory tract infections were entered into this multicentre, General Practice, investigator-blind study, designed to demonstrate equivalent efficacy between clarithromycin and amoxycillin suspensions. Seventy one children were randomised to treatment with clarithromycin suspension 7.5 mg/kg bodyweight twice daily and 74 to treatment with amoxycillin suspension 125 mg (bodyweight < 25 kg) or 250 mg (bodyweight > or = 25 kg) three times a day according to bodyweight. Duration of therapy was 5-10 days as determined by the investigator. Clinical evaluations were performed pretreatment, during treatment and post-treatment within 72 hours of cessation of therapy. Fifty two children in the clarithromycin group and 57 in the amoxycillin group were clinically evaluable. Both study medications were effective and there were no significant differences between the groups with respect to clinical cure rate (60% for clarithromycin and 63% for amoxycillin), clinical success rate (cure plus improvement, 96% for clarithromycin and 95% for amoxycillin) or rate of resolution of clinical signs and symptoms in clinically evaluable patients. The intention to treat analysis for all patients entered similarly showed no significant differences in efficacy. The two treatment groups did not differ significantly with respect to incidence or severity of adverse events which were generally mild and associated with the gastrointestinal system. Therapy was withdrawn because of adverse events in three children on clarithromycin and one on amoxycillin. Bacteriological cure rates could not be determined because of an insufficient number of evaluable pre-treatment sputum samples.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical evaluation of Augpenin (clavulanic acid-ticarcillin) in urinary tract infections: especially against beta-lactamase producing strains

Augpenin contains ticarcillin (TIPC) and clavulanic acid (CVA), at a ratio of 15:1. The beta-lactamase inhibitor, CVA, has been added to protect the TIPC from inactivation by beta-lactamase. To investigate the drug efficacy and safety against urinary tract infections (UTI), Augpenin was administered to 33 patients with chronic complicated UTI and 7 patients with acute pyelonephritis. Thirty two cases were evaluable by the UTI criteria. Excellent results were obtained in 6 of the cases of acute pyelonephritis, and moderate results in 1 case, with an overall effectiveness rate of 100%. Excellent results were obtained in 14 of the cases of chronic complicated UTI, moderate results in 9 cases, and poor results in 2 cases, with an overall effectiveness rate of 92%. No adverse reactions were noted, but a transient elevation of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase levels was observed in 2 cases.     

Vaginal mucosal immunization for recurrent urinary tract infection: phase II clinical trial

PURPOSE: Decreased local immunity to uropathogenic bacteria may be a factor predisposing women to recurrent urinary tract infections. Our phase I study demonstrated the safety of a multi-strain vaccine administered as a vaginal suppository. A phase II study was conducted to determine vaccine efficacy. MATERIALS AND METHODS: A total of 91 women susceptible to recurrent urinary tract infections was entered into the study and the courses were analyzed in a randomized, double-blind, placebo controlled trial of vaginal mucosal immunization. Subjects received 3 vaginal suppositories at weekly intervals. Depending on the treatment group each suppository contained 1 of 2 vaccine doses or suppository material only. Each patient was followed for 5 months to record infection episodes, and obtain urine, vaginal irrigates and serum to measure immunological responses. RESULTS: Immunogen treated women who were off antibiotic prophylaxis throughout the study had a significant delay in interval to reinfection during the first 8 weeks compared to women receiving placebo. Mean interval until reinfection was delayed from 8.7 weeks for placebo treated to 13 weeks for vaccine treated women. Immunological responses in serum, urine and vaginal fluid were variable. No serious adverse effects were observed. CONCLUSIONS: These data demonstrate that vaginal mucosal immunization can enhance resistance to urinary tract infections in susceptible patients.     

Pharmacokinetics and pharmacodynamics of bumetanide in critically ill pediatric patients

This prospective, open-label, clinical trial was conducted to describe the pharmacology of bumetanide in pediatric patients with edema. Nine infants, children, and young adults with edema who were selected for diuretic therapy were studied. After a brief baseline period, each patient received parenteral bumetanide 0.2 mg/kg divided into two equal doses and administered every 12 hours. Urine excretion rate, fractional and total excretion of Na+, Cl-, and K+, creatinine clearance, and plasma and urine concentrations of bumetanide were measured at multiple intervals after drug administration. Bumetanide caused significant increases in the excretion rate of urine and each measured electrolyte. Unexpectedly, creatinine clearance increased dramatically after each dose. Adverse effects, including hypokalemia and hypochloremic metabolic alkalosis, were evident by the end of the treatment period. The plasma pharmacokinetics of bumetanide revealed mean +/- standard deviation values for total clearance and apparent volume of distribution of 3.9 +/- 2.4 mL/min/kg and 0.74 +/- 0.54 L/kg, respectively. Patients excreted an average of 34% of each dose unchanged in the urine over 12 hours. Plasma concentrations of bumetanide accurately predicted several renal effects using a link model with similar pharmacodynamic parameters in each case. Parenteral bumetanide 0.1 mg/kg administered every 12 hours produced significant beneficial and adverse effects in these critically ill pediatric patients with edema. Pharmacokinetic parameters are similar to those previously reported for infants. Plasma concentrations of bumetanide can predict effect-compartment pharmacodynamics.