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BACKGROUND Moxifloxacin is an advanced-generation fluoroquinolone used primarily for the treatment of respiratory tract infections. OBJECTIVE To further investigate moxifloxacin's general and cardiac safety and evaluate its efficacy in the community practice setting in a large surveillance study. METHODS A total of 18 409 outpatients with suspected bacterial episodes of acute sinusitis, acute exacerbation of chronic bronchitis, or community-acquired pneumonia of mild to moderate severity were enrolled at 3377 community practice sites. Patients with sinusitis or pneumonia received once-daily oral moxifloxacin 400 mg for 10 days; those with bronchitis received 5 days' treatment. At follow-up, within 48 hours after the end of treatment, adverse event information was collected. An external safety committee assessed possible cardiac-related events. Efficacy was also evaluated at follow-up via the degree of resolution of clinical signs and symptoms. RESULTS Of 18 374 safety-valid patients, 17.7% experienced adverse events and 14.3% experienced drug-related adverse events. The most common drug-related adverse events were nausea (5.3%), diarrhea (2.2%), and dizziness (2.0%). There was no clinical evidence of increased risk of cardiac arrhythmias with moxifloxacin treatment. Of 17 137 patients included in the efficacy analysis, 92.9% overall experienced clinical cure or improvement (92.8% with sinusitis, 92.9% with bronchitis, 94.1% with pneumonia). CONCLUSIONS Once-daily oral moxifloxacin 400 mg was shown to be safe and effective in this trial for the treatment of respiratory tract infections of suspected bacterial origin in the clinical practice setting.

We assessed the efficacy and safety of 1,000 mg extended release ciprofloxacin orally once daily vs conventional 500 mg ciprofloxacin orally twice daily, each for 7 to 14 days, in patients with a complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis (AUP).In this prospective, randomized, double-blind, North American multicenter clinical trial adults were stratified based on clinical presentation of cUTI or AUP and randomized to extended release ciprofloxacin or ciprofloxacin twice daily. Efficacy valid patients had positive pretherapy urine cultures (105 or greater cFU/ml) and pyuria within 48 hours of study entry. Bacteriological and clinical outcomes were assessed at the test of cure visit (5 to 11 days after therapy) and the late followup visit (28 to 42 days after therapy).The intent to treat population comprised 1,035 patients (extended release ciprofloxacin in 517 and twice daily in 518), of whom 435 were efficacy valid (cUTI in 343 and AUP in 92). For efficacy valid patients (cUTI and AUP combined) bacteriological eradication rates at test of cure were 89% (183 of 206) vs 85% (195 of 229) (95% CI -2.4%, 10.3%) and clinical cure rates were 97% (198 of 205) vs 94% (211 of 225) (95% CI -1.2%, 6.9%) for extended release vs twice daily ciprofloxacin. Late followup outcomes were consistent with test of cure findings. Eradication rates for Escherichia coli, which accounted for 58% of pathogens, were 97% or greater per group. Drug related adverse event rates were similar for extended release and twice daily ciprofloxacin (13% and 14%, respectively).Extended release ciprofloxacin at a dose of 1,000 mg once daily was as safe and effective as conventional treatment with 500 mg ciprofloxacin twice daily, each given orally for 7 to 14 days in adults with cUTI or AUP. It provides a convenient, once daily, empirical treatment option.

Background: Trimethoprim/sulfamethoxazole (TMP/SMX) is currently the first choice for empiric therapy of acute uncomplicated urinary tract infection (UTI) in women. In areas where resistance to TMP/SMX is known to be high, ciprofloxacin and other fluoroquinolones are recommended as first-line choices for the empiric therapy of UTI. Objective: This study compared the efficacy and safety profile of once-daily extended-release ciprofloxacin 500 mg (referred to hereafter as ciprofloxacin QD) with those of conventional ciprofloxacin 250 mg BID, each administered orally for 3 days, in the treatment of uncomplicated UTI in women. Methods: In this multicenter, prospective, randomized, double-blind, double-dummy, Phase III trial, adult women with clinical signs and symptoms of acute uncomplicated UTI, pyuria, and a positive pretherapy urine culture (≥10 5 colony - forming units / mL ) received ciprofloxacin QD or ciprofloxacin BID. Bacteriologic and clinical outcomes were assessed at the test-of-cure visit (4–11 days after completion of therapy) and the late follow-up visit (25–50 days after completion of therapy). Results: The intent-to-treat population consisted of 891 patients (444 ciprofloxacin QD, 447 ciprofloxacin BID); 422 patients were evaluable for efficacy (199 ciprofloxacin QD, 223 ciprofloxacin BID). At the test-of-cure visit, bacteriologic eradication was achieved in 94.5% (188/199) of the ciprofloxacin QD group and 93.7% (209/223) of the ciprofloxacin BID group (95% CI, −3.5 to 5.1). Clinical cure was achieved in 95.5% (189/198) of the ciprofloxacin QD group and 92.7% (204/220) of the ciprofloxacin BID group (95% CI, −1.6 to 7.1). Bacteriologic and clinical outcomes at the late follow-up visit were consistent with the test-of-cure findings. The rate of eradication of Escherichia coli , the most prevalent organism, was >97% in each treatment group. Rates of drug-related adverse events were similar with the once- and twice-daily ciprofloxacin regimens (10% and 9%, respectively). Conclusion: Extended-release ciprofloxacin 500 mg given once daily for 3 days was as effective and well tolerated as conventional ciprofloxacin 250 mg given twice daily for 3 days in the treatment of acute uncomplicated UTI in women.

To determine the efficacy and safety of single-dose oral ciprofloxacin prophylaxis for the prevention of post-operative bacteriuria following transurethral resection of the prostate or bladder tumour, a prospective, randomized, double-blind, placebo-controlled trial was conducted. Five hundred and eighteen patients were randomized in a 2:2:1 ratio to receive ciprofloxacin 500 mg, cefotaxime 1 g or placebo 30- 90 min before surgery. Of the 368 efficacy-evaluable patients, five (3.3%) ciprofloxacin, seven (4.8%) cefotaxime and five (7.0%) placebo recipients had post- operative bacteriuria (≥10 4 cfu/mL) during post-operative days 2- 15. Five (3.4%) ciprofloxacin, five (3.4%) cefotaxime and one (2.4%) placebo recipients were considered clinical failures, of whom one, two and one patients, respectively, had concomitant bacteriuria. Drug-related adverse events were reported in six of 204 (3%) ciprofloxacin, 12 of 197 (6%) cefotaxime and one of 101 (1%) placebo patients. The observed rates of post-operative bacteriuria suggest that a single 500 mg dose of ciprofloxacin is suitable prophylaxis for transurethral surgery.

The study was undertaken to compare the safety and efficacy of twice-daily ciprofloxacin for 3 days with standard 7 day therapy with either co-trimoxazole or nitrofurantoin in the treatment of women with acute, uncomplicated urinary tract infections (UTI). This multicentre, prospective, randomized, double-blind trial compared oral ciprofloxacin (100 mg bd) for 3 days with co-trimoxazole (160/800 mg bd) or nitrofurantoin (100 mg bd) for 7 days. Bacteriological and clinical evaluations were performed at study entry, during therapy and 4-10 days and 4-6 weeks after the completion of therapy. The primary efficacy parameter was eradication of the causative organism 4- 10 days following treatment. Of 713 women enrolled and evaluable for safety, 521 were evaluable for efficacy (168 ciprofloxacin, 174 co-trimoxazole, 179 nitrofurantoin). Escherichia coli (83%) was the most frequently isolated pathogen in all treatment groups. Bacteriological eradication was reported in 88% of ciprofloxacin patients, 93% of co-trimoxazole patients and 86% of nitrofurantoin patients. At the 4-6 week follow-up, ciprofloxacin had statistically significantly higher eradication rates (91%) than co-trimoxazole (79%; 95% confidence limit (CL) = −20.6%, −3.9%) and nitrofurantoin (82%; 95% CL = −17.1%, −0.9%). Clinical resolution 4- 10 days after therapy and at the 4- 6 week follow-up was similar among the three treatment groups. The overall incidence of treatment-emergent adverse events was not significantly different (P= 0.093) among the three drug regimens, althousgh co-trimoxazole was associated with a greater number of adverse events than ciprofloxacin (P ≤0.05). Ciprofloxacin also caused fewer episodes of nausea than either of the other agents (P ≤0.01).

Fifty-nine patients returned a confidential mailed questionnaire, to determine their procedures for disposal of CAPO waste including bags, fluids and needles, and to assess their instruction and opinions on health risks from their wastes. Patients came predominantly from rural communities. Sixty four percent used disposal boxes for used needles, 80% discarded drained bags in the garbage without wrapping them in plastic and 7 to 17% of patients discarded needles straight to the garbage, depending on circumstances. Thirty seven percent did not recall receiving instruction on waste disposal, and of those who did, instructions came predominantly from nurses. Twenty of 32 patients who had suffered peritonitis disposed of their bags during peritonitis in the same manner as when they did not have peritonitis. Most patients (61%) felt issues dealing with CAPO waste disposal were “important” or “very important”, but fewer “agreed” or “strongly agreed” that it posed a health risk to others (16%) or to the environment (10%). Inconsistencies in methods of disposal and potential risks of infection dictate that guidelines must be developed to deal with these issues.

We compared the bactericidal activity of serum obtained from healthy volunteers after single intravenous infusions of the combination of ceftizoxime (1 g) plus metronidazole (1 g) and after infusions of ceftizoxime (2 g), clindamycin (900 mg), and imipenem (1 g) against six obligate anaerobes. All agents were bactericidal but only the combination regimen resulted in bactericidal titres greater than 1:2 at 12 h for all the Bacteroides fragilis group organisms. High titres against Fusobacterium necrophorum and anaerobic Gram-positive cocci were attained with ceftizoxime/metronidazole, ceftizoxime, and imipenem 12 h after the dose. Imipenem and the combination of ceftizoxime/metronidazole had the greatest area under the bactericidal curve (AUBC) against the Bacteroides species. Clindamycin had a significantly smaller AUBC than other regimens for all strains tested except B. thetaiotaomicron. Clinical trials are needed to assess the efficacy and cost-benefit ratio of a 12 h dosing regimen of ceftizoxime in combination with metronidazole for treating mixed aerobic/anaerobic infections.

Objective To compare the efficacy and safety of faropenem medoxomil, 300 mg twice daily for seven or ten days, with cefuroxime axetil 250 mg twice daily for ten days in adults with acute bacterial sinusitis (ABS). Study design and setting Prospective, double-blinded, phase III trial with entry criteria consistent with FDA/IDSA guidelines for diagnosis of ABS. Primary efficacy parameter was clinical response at 7 to 21 days posttherapy. Results One thousand ninety-nine subjects were randomized and treated; 861 were efficacy valid. Clinical cure rates were 80.3% for seven days of faropenem, 81.8% for ten days of faropenem, and 74.5% for 10 days of cefuroxime axetil. The incidence of adverse events and premature discontinuations were similar for the three treatment regimens. Conclusions Seven- and ten-day faropenem medoxomil regimens were similar (noninferior) to a ten-day cefuroxime axetil regimen based on clinical response in patients with ABS. Significance A seven-day course of faropenem medoxomil 300 mg twice-daily regimen is a promising alternative for treatment of ABS.

In this prospective, double-blind, multicentre trial, adult patients with complicated skin and skin structure infection (cSSSI) randomly received sequential intravenous (i.v.)/oral (p.o.) moxifloxacin (400 mg once a day) or a control regimen of i.v. piperacillin-tazobactam (3.0/0.375 g every 6 h) followed by p.o. amoxicillin-clavulanate (800 mg every 12 h), each for 7-14 days. Clinical cure rates at the test-of-cure visit (10-42 days post therapy) for the efficacy-valid population were 79% (143/180) for the moxifloxacin-treated group and 82% (153/187) for the control group (95% confidence interval, -12.04, 3.29). Bacteriological eradication rates for Staphylococcus aureus, the most prevalent organism, were 78% and 80%, respectively. The incidence of drug-related adverse events was similar for both groups (31% moxifloxacin, 30% control). Sequential i.v./p.o. moxifloxacin was as effective and well tolerated as i.v. piperacillin-tazobactam followed by p.o. amoxicillin-clavulanate in treating patients with cSSSI.

BACKGROUND Therapy with an aminoglycoside and a beta-lactam remains common empirical therapy for febrile neutropenic patients. Concerns of aminoglycoside-induced ototoxicity and nephrotoxicity have led to studies of alternate regimens. OBJECTIVE To determine whether ciprofloxacin-piperacillin is equivalent to tobramycin-piperacillin as empirical therapy for neutropenic fever. DESIGN Randomized, double-blind multicenter trial. SETTING Seven U.S. university-affiliated hospitals and one private research center. PATIENTS Febrile (temperature >/= 38 degrees C), neutropenic (neutrophil level < 1 x 10(9) cells/L) hospitalized patients who had leukemia, lymphoma, or solid tumors, or were undergoing bone marrow transplantation. INTERVENTIONS Patients received piperacillin, 50 mg/kg of body weight intravenously every 4 hours, and ciprofloxacin, 400 mg intravenously every 8 hours, or tobramycin, 2 mg/kg intravenously every 8 hours. MEASUREMENTS Success was defined as resolution of infection and previously positive cultures without the need to give additional antimicrobial agents. RESULTS 543 febrile episodes were evaluated, of which 471 were clinically evaluable (234 in the ciprofloxacin-piperacillin group and 237 in the tobramycin-piperacillin group). Success rates in the ciprofloxacin-piperacillin group (63 of 234 febrile episodes) and tobramycin-piperacillin group (52 of 237 episodes) were similar (27% vs. 22%, respectively; difference, 5.0 percentage points [95% CI, -2.3 to 12.8 percentage points]), as was survival (96.2% of patients receiving ciprofloxacin-piperacillin versus 94.1% of patients receiving tobramycin-piperacillin; difference, 2.1 percentage points [CI, -2.2 to 6.4 percentage points]). Additions to the initial antimicrobial regimen were the most common reason for treatment failure in both groups (accounting for 67% of failures in the ciprofloxacin-piperacillin group and 72% in the tobramycin-piperacillin group; difference, 5.0 percentage points [CI, -13.8 to 3.7 percentage points]). Fevers resolved faster in patients receiving ciprofloxacin-piperacillin than in patients receiving tobramycin-piperacillin (mean, 5 vs. 6 days) (P = 0.005). No significant differences in adverse events or toxicity were noted (P = 0.083). CONCLUSION Ciprofloxacin-piperacillin is as safe and effective as tobramycin-piperacillin for empirical therapy of neutropenic fever.

The treatment of intraabdominal infection is challenging because of their polymicrobial nature 1–3 and accompanying death and complications. Treatment may be further complicated by bacteriologic resistance issues, such as the large number of β-lactamase-producing Enterobacteriaceae present in intraabdominal infections. For most episodes, antimicrobial regimens usually involve combination therapy, 4–11 although several monotherapy approaches have been studied. 5,6,12–15 Ciprofloxacin (CIP), a 1-cyclopropyl fluoroquinolone, has excellent activity against aerobic gram-negative facultative microbes commonly associated with intraabdominal infections 16,17 and also penetrates well into the peritoneal cavity. 18,19 In this study, CIP was used in combination with metronidazole (MET), which has proven efficacy in the treatment of intraabdominal infections. 13 One important advantage of CIP+MET combination therapy over conventional antibiotic regimens is that it permits patients to be switched from intravenous (IV) to oral therapy, thus maintaining the same antibiotic class and providing consistent susceptibility. Because of the excellent bioavailability of CIP (70%), 20 oral CIP 500 mg twice daily is bioequivalent to 400 mg of intravenous CIP q12h. 19 Treatment of serious abdominal infections with oral therapy can allow recovery at home, potentially lowering the risk of acquiring a nosocomial or IV catheter-related complication. Obviously, limiting the duration of hospital stay and also antimicrobial costs is desirable in the current healthcare environment. The primary objective of this study was to compare the efficacy of IV CIP+MET with IV piperacillin/tazobactam (PIP/TAZO) for the treatment of complicated intraabdominal infections. A secondary goal was to compare the efficacy of IV CIP+MET alone with sequential IV-to-oral CIP+MET therapy. We hypothesized that CIP+MET would provide equivalent clinical resolution to the PIP/TAZO regimen.

Objectives. To determine whether antimicrobial prophylaxis could prevent infections after transrectal needle biopsy of the prostate using automated biopsy devices. Methods. We conducted a prospective, randomized, double-blind, multicenter trial in which a total of 537 patients received either oral ciprofloxacin 500 mg or placebo before transrectal needle biopsy of the prostate. Repeated urine cultures and urinalysis were obtained at 2 to 6 days after biopsy and 9 to 15 days after biopsy. The primary determinant of efficacy was bacteriologic response (bacteriuria [more than 10 4 colony-forming units (CFU)/mL] versus no bacteriuria) at the 9- to 15-day follow-up evaluation. Results. Two hundred twenty-seven (84%) of 269 ciprofloxacin patients and 230 (86%) of 268 placebo patients were valid for efficacy analysis in which a mean of four biopsies was performed. Six ciprofloxacin-treated (3%) and 19 placebo-treated (8%) patients had bacteriuria (more than 10 4 CFU/mL) after the procedure ( P = 0.009). Six ciprofloxacin recipients (3%) and 12 placebo recipients (5%) had clinical signs and symptoms of a urinary tract infection (UTI) ( P = 0.15). In addition, no ciprofloxacin-treated patients compared with 4 placebo-treated patients (2%) were admitted to the hospital for febrile UTI after the procedure. Ciprofloxacin reduced the expected net costs of treating infectious complications after biopsy by $23 per patient for an overall annual savings of $68,195 in the five study groups when compared with placebo. Conclusions. Single-dose oral ciprofloxacin reduced bacteriuria after biopsy compared with placebo in patients undergoing transrectal prostatic biopsy and provided an economic advantage. In addition, this study establishes the actual rate of bacteriuria after transrectal needle biopsy of the prostate without antibiotic prophylaxis to be 8% with a clinical rate of UTI of 5% and a hospitalization rate of 2%.

In a review of the US Bayer ciprofloxacin (CIP) database, an analysis was undertaken to summarize the effectiveness and tolerability of CIP 750 mg BID in the treatment of patients with acute exacerbations of chronic bronchitis (AECB) and pneumonia. In five controlled studies, comparator (COMP) agents included ampicillin, intravenous cefuroxime/cefaclor, and other unspecified agents. Primary efficacy end points were clinical success (resolution plus improvement) and bacteriologic eradication at the end of therapy. The incidence of adverse events for CIP 750 mg BID was compared with that for COMP and with that in the CIP 500-mg-BID AECB and pneumonia clinical trials database. In five uncontrolled studies, 443 patients received CIP 750 mg BID; in 5 controlled trials comprising 344 patients, 169 received CIP 750 mg BID and 175 received COMP. Clinical success for CIP was 93% (368/396) and 99% (160/162), respectively, in the uncontrolled and controlled studies versus 98% (156/160) for COMP agents. Corresponding bacteriologic eradication rates for CIP 750-mg-BID-treated patients were 77% (273/356) and 95% (122/128), respectively, and 77% (96/125) for COMP agents. Overall bacteriologic eradication by organism for CIP 750 mg BID included Streptococcus pneumoniae 96% (51/53), Haemophilus influenzae 98% (92/94), Haemophilus parainfluenzae 100% (56/56), Moraxella catarrhalis 100% (14/14; 13 of 14 organisms were isolated in patients with AECB), and Pseudomonas aeruginosa 66% (135/204). Drug-related adverse events were reported in 113 (26%) CIP 750-mg-BID-treated patients in uncontrolled trials and in 62 (37%) CIP 750-mg-BID- and 61 (35%) COMP-treated patients in controlled trials. In the combined data from the CIP 750-mg-BID uncontrolled and controlled trials, adverse events occurred with similar frequency compared with COMP except for nausea (CIP 10%, COMP 7%) and diarrhea (CIP 3%, COMP 13%). In conclusion, CIP 750 mg BID provided excellent clinical success rates in the treatment of patients with AECB and pneumonia. CIP 750 mg BID was well tolerated compared with the COMP agents administered.

We studied the enteric absorption of ciprofloxacin immediately following major abdominal surgery to determine if this drug could replace parenteral agents. Nine critically ill subjects received ciprofloxacin, 750 mg, every 12 h for 48 h via nasogastric tube. Drug concentrations were measured after the first and fourth doses. There was insignificant absorption after the initial dose, Cmax = 0.6 +/- 0.6 (mg/L) and AUC0-12 = 3.5 +/- 3.2 (mg.h/L). Unfortunately, serum ciprofloxacin concentrations were also minimally detectable in three of nine subjects after the fourth dose. Enteric absorption of ciprofloxacin, therefore, was erratic and unpredictable in critically ill patients following major abdominal surgery.

OBJECTIVE: The primary objective of this article is to introduce readers to the use of a new agent, trimetrexate (TMTX), in the treatment of Pneumocystis carinii pneumonia (PCP). The article also gives the readers an overview of PCP and discusses some of the controversies surrounding it. Pharmacokinetic data and clinical trials are reviewed, as well as adverse effects, drug interactions, and dosage guidelines. DATA SOURCES: A MEDLINE search was used to identify pertinent literature, including reviews. STUDY SELECTION: As both pharmacokinetic and clinical trials were few in number, all available trials were reviewed. DATA EXTRACTION: Pharmacokinetic data from trials involving patients with AIDS was sparse; therefore, those involving oncology patients, including a pediatric population, were included. Although more trials need to be done in AIDS patients, the results from the oncologic trials give us a baseline from which to extrapolate. All clinical trials available at the time of publication were reviewed as were all of the preliminary results from three ongoing trials, which were made available through a personal communication. DATA SYNTHESIS: TMTX has been found to be 1500 times more potent than trimethoprim as a dihydrofolate reductase inhibitor, and has the potential to provide an effective therapeutic option for PCP. TMTX is a lipid-soluble analog of methotrexate and is thus capable of greater penetration into Pneumocystis cells, which lack the folate membrane transport system necessary to take up classic folate structures like leucovorin and methotrexate, thereby negating any clinical effectiveness of methotrexate and allowing leucovorin to be used for host cell rescue. TMTX's pharmacokinetic parameters best fit a multicompartmental model with a terminal half-life of up to 12 hours. It is cleared both hepatically and renally with up to 41 percent excreted unchanged in the urine. Although TMTX's pharmacokinetic parameters are variable, the need for plasma concentration monitoring at present is unclear, as no dose-response relationship has been established. Efficacy trials involving TMTX have been conducted mostly in patients with moderate to severe PCP who were either intolerant and/or refractory to standard therapies. Response rates to TMTX therapy have ranged from 6 to 90 percent, thereby demonstrating that TMTX may be useful in the treatment of certain patients with PCP. CONCLUSIONS: Although more well-designed clinical trials comparing TMTX with standard therapies are necessary, initial results indicate that TMTX is a promising alternative for moderate to severe episodes of PCP. Also, additional studies of TMTX's use as a prophylactic agent in PCP, and when it should be initiated in relation to a patient's CD4 count are needed. Furthermore, difficulty may arise in using TMTX on a regular basis because of the potential cost of therapy with concomitant leucovorin.

Background: Three studies were undertaken to determine the minimum effective dosing regimen of ciprofloxacin for the treatment of acute, symptomatic, uncomplicated lower urinary tract infection. Methods: All studies were multicenter, prospective, randomized, double-blind trials. A total of 970 evaluable patients with a diagnosis of urinary tract infection received oral ciprofloxacin (200 mg to 500 mg daily in one or two divided doses for 1, 3, 5, or 7 days) or norfloxacin (400 mg twice daily [BID] for 7 days). The primary measure of efficacy was bacteriologic eradication at the end of therapy. Results: In study 1, bacteriologic eradication was reported in 95 (89%) and 101 (98%) of patients in the groups who received ciprofloxacin, 500-mg single dose and 250 mg BID for 7 days, respectively. Clinical success occurred in 101 patients (94%) who received a 500-mg single dose and in 103 patients (100%) who were administered 250 mg BID for 7 days. In study 2, eradication rates in the groups who received ciprofloxacin, 100 mg BID for 3 days, 250 mg BID for 3 days, and 250 mg BID for 7 days, were 98 (93%), 95 (90%), and 98 (93%), respectively. Clinical success was reported in 102 (97%), 105 (100%), and 104 (98%) of the patients, respectively. In study 3, the eradication rates in the groups who received ciprofloxacin in dosages of 500 mg once daily for 3 days and 500 mg once daily for 5 days and norfloxacin in a dosage of 400 mg BID for 7 days were 137 (92%), 134 (90%), and 133 (94%) of the women, respectively. Clinical success was the same (97%) in all three groups. Overall, short-course (either 3- or 5-day) therapy with ciprofloxacin was statistically equivalent to conventional (7-day) therapy with either ciprofloxacin or norfloxacin. Single-dose ciprofloxacin therapy was statistically less effective than conventional treatment. Conclusions: Ciprofloxacin at a dosage of 100 mg BID for 3 days was the minimum effective dose for the treatment of uncomplicated urinary tract infection in women. (Arch Intern Med. 1995;155:485-494)

• Numerous toxic exposures have been implicated in causing aplastic anemia. Thirteen cases of aplastic anemia and 5 cases of other blood dyscrasias, eg, red blood cell aplasia and thrombocytopenia, associated with lindane, have been reported in the literature. However, aplastic anemia secondary to the scabicidal product (lindane [Kwell]) has not been documented, to our knowledge. We present the case of a 21-year-old man with a diagnosis of aplastic anemia, known prolonged exposure to lindane, and documented elevated serum lindane levels. His clinical course is described as well as various defects are explored for the aplasia. (Arch Intern Med.1990;150:2393-2395)

The relationship between creatinine clearance changes during gentamicin therapy and several patient and therapeutic variables was studied in a prospective, multicenter trial. Adult patients in three hospitals who were receiving gentamicin in doses based on lean body weight and creatinine clearance were studied. Pre- and post-therapy serum creatinine measurements were obtained for 62 patients (Group 1); only 45 of the patients had both pre- and post-therapy creatinine clearance measurements (Group 2). Other data collected for correlation with creatinine clearance changes were: body temperature, age, sex, blood pressure, albumin level, previous and concomitant therapy with nephrotoxic drugs, hematocrit, peak and trough gentamicin levels, and duration of therapy. In Group 2 patients, only peak gentamicin level, concomitant therapy, sex, and previous furosemide therapy correlated significantly (p less than or equal to 0.05) with change in creatinine clearance during gentamicin therapy. The first two variables decreased creatinine clearance, the last variable increased creatinine clearance, and women tended to have more of a decrease in clearance than did men. Sex, peak gentamicin level, prior furosemide therapy and concomitant cephalothin therapy explain about 50% of the renal function changes during gentamicin therapy, and should be considered in monitoring gentamicin therapy.

The use of cimetidine, an H2-receptor antagonist, to minimize the complications of acid aspiration pneumonia is reviewed. Since Mendelson's early description of acid aspiration in 66 obstetrical patients, attempts have been made to decrease gastric acidity by administering perioperative antacids and/or antihistamine drugs such as atropine and glycopyrrolate. In this review of the literature, strict attention is given to study design and subject selection, methods of collecting gastric samples and reporting both pH and volume measurements, and medications taken on admission, given preoperatively, and as anesthetics. Clinical trials evaluating cimetidine alone and compared with other prophylactic regimens were reviewed, detailing the timing, route, and frequency of drug administration. Cimetidine appears to be effective in minimizing complications of acid aspiration since gastric acidity (pH < 2.5) is a contributing factor in both the morbidity and mortality of this disease state. In general terms, cimetidine 300 mg po 1.5–2.0 h prior to intubation or 45–60 minutes iv before surgery will decrease gastric acidity below the critical level. This effect may be maintained for up to three hours. Perioperative cimetidine administration, to minimize the complications of acid aspiration, appears to be safe in terms of drug-drug interactions and effects on labor, the fetus, and the newborn child.

The impact of a pharmacy-conducted intervention program designed to contain costs by "streamlining" antimicrobial therapy is described. Streamlining of antimicrobial therapy may involve simplifying routes of administration, decreasing the dose or frequency of antimicrobial administration, or converting from multiple-agent therapy to single-agent therapy. Beginning on December 1, 1987, pharmacists at this university-affiliated teaching hospital used the antimicrobial order sheet (AOS) filled out by all prescribers of anti-infective agents to identify orders that were potential candidates for streamlining. Interventions involved a discussion between the pharmacist and prescriber in which the pharmacist specified the reasoning behind the recommended change. For each recommendation that was accepted by the prescriber, the cost savings per day was determined by subtracting the daily cost of the recommended streamlined therapy from the daily cost of the original "problem" therapy. Data collection continued until May 1, 1988. During that five-month period, 162 out of 173 pharmacist-initiated streamlining recommendations were accepted by prescribers, resulting in a total cost savings of $19,864. The average cost savings per intervention was $122.62. The most frequent intervention involved decreasing the frequency of i.v. administration, decreasing the dose, or both. The intervention that resulted in the greatest average cost savings involved simplifying the route of administration or discontinuing antimicrobial therapy entirely. The projected annual cost savings of this program is $47,700. By using information from AOSs to identify problem antimicrobial orders, pharmacists were able to recommend streamlining of antimicrobial therapies that resulted in an average cost savings of about $122 per intervention.

An antibiotic order form was implemented for all inpatient antibiotic orders at an 800-bed hospital in April 1981 to provide an ongoing, concurrent audit of antibiotic use. The prescribing physician provided the clinical indication for the antibiotic order, and individual patient treatment courses were identified. During the 25-month study period, cephalosporins, penicillin plus ampicillin, and aminoglycosides accounted for 44%, 22%, and 17% of all treatment courses, respectively. Sixty-nine percent of first-generation cephalosporin treatment courses were for prophylaxis, whereas the remaining antibiotics were used for either empirical therapy or documented infection in 56%-79% of cases. After the introduction of the antibiotic order form, there was a significant decline in both the number of antibiotic treatment courses (P = .025) and the percentage of patients receiving any antibiotic (P = .007). We conclude that a specialized antibiotic order form is an effective method for antibiotic utilization review and can have a significant impact on a physician's prescribing patterns.

Thirty-eight patients were treated with cefamandole 6–12 g/d. These included 24 patients with cellulitis and/or abscess and 14 with osteomyelitis or septic arthritis. Two patients were bacteremic. Of the patients treated, 26 had an underlying disease; 27 required some surgical procedure. Staphylococcus aureus was the most frequent bacteria isolated. Of 38 patients treated, 31 had a clinical cure, six were unevaluable, and one failed on therapy. Twelve patients developed a reaction to the drug. Average peak serum level after cefamandole 1 g iv was 30.6 μg/ml (range, 10–67 μg/ml); average peak serum level after 2 g iv was 39.9 μg/ml (range, 6.6–110 μg/ml). Cancellous bone concentrations in two patients ranged from 6 to 7 μg/ml, and cortical bone concentrations in five patients ranged from 10 to 28 μg/ml.

Cefoxitin, a new β-lactamase-resistant cephamycin, was evaluated in 66 patients for clinical and bacteriological efficacy, serum levels, tolerance, and toxicity. Seventeen patients had soft tissue infections, 14 had pleuropulmonary infections, 14 had intraabdominal infections, 13 had pelvic infections, and 8 had urinary tract infections. Among the 66 patients, 62 were cured and 4 could not be evaluated. Twelve patients had hospital-acquired infections, 31 had underlying disease, and 45 required a surgical procedure. Isolates included 116 aerobic and 72 anaerobic bacteria. Cefoxitin was more active than cephalothin against facultative and obligate anaerobic gram-negative organisms isolated from these patients. Mean peak cefoxitin levels in sera were 52 μg/ml after a 2-g infusion and 30 μg/ml after a 1-g infusion. Phlebitis occurred in two patients, eosinophilia in one, rash in two, vasculitis in one, and transient rises in SGOT and SGPT in two. Cefoxitin appears to be a safe and effective drug for the treatment of many aerobic, anaerobic, and mixed aerobic-anaerobic infections.