A multi-center randomised controlled trial of gatifloxacin versus azithromycin for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. Short course of ofloxacin for treatment of multidrug-resistant typhoid. Single-dose fluoroquinolone therapy of acute uncomplicated urinary tract infection in women: results from a randomized, double-blind, multicenter trial comparing single-dose to 3-day fluoroquinolone regimens. Ciprofloxacin versus ceftriaxone in the treatment of multiresistant typhoid fever. Short courses of ofloxacin for the treatment of enteric fever. Implementation of guidelines for sequential therapy with fluoroquinolones in a Belgian hospital. Long-term study of fluticasone propionate aqueous nasal spray in acute and maintenance therapy of nasal polyposis. Fluticasone propionate aqueous nasal spray in the treatment of nasal polyposis. A Phase II study of the sterilising activities of ofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Pefloxacin versus chloramphenicol in the therapy of typhoid fever. Prospective randomized comparative trial of pefloxacin versus cotrimoxazole in the treatment of typhoid fever in adults. Multicenter, randomized comparative trial of fludarabine and the combination of cyclophosphamide-doxorubicin-prednisone in 92 patients with Waldenström macroglobulinemia in first relapse or with primary refractory disease. Gatifloxacin versus chloramphenicol for uncomplicated enteric fever: an open-label, randomised, controlled trial. Fluoroquinolone prophylaxis for bacterial infections in neutropenic patients with hematologic malignancies. Ciprofloxacin, lomefloxacin, or levofloxacin as treatment for chronic osteomyelitis. Effect of fluticasone in severe polyposis. Fluticasone propionate compared with theophylline for mild-to-moderate asthma. Atovaquone and proguani hydrochloride compared with chloroquine or pyrimethamine/sulfodaxine for treatment of acute Plasmodium falciparum malaria in Peru. Flunisolide nasal spray 0.025% in the prophylactic treatment of nasal polyposis after polypectomy. A randomized, double blind, parallel, placebo controlled study.
Drug resistant typhoid fever is a major clinical problem globally. Many of the first line antibiotics, including the older generation fluoroquinolones, ciprofloxacin and ofloxacin, are failing.
                We performed a randomised controlled trial to compare the efficacy and safety of gatifloxacin (10 mg/kg/day) versus azithromycin (20 mg/kg/day) as a once daily oral dose for 7 days for the treatment of uncomplicated typhoid fever in children and adults in Vietnam.
                An open-label multi-centre randomised trial with pre-specified per protocol analysis and intention to treat analysis was conducted. The primary outcome was fever clearance time, the secondary outcome was overall treatment failure (clinical or microbiological failure, development of typhoid fever-related complications, relapse or faecal carriage of S. typhi).
                We enrolled 358 children and adults with suspected typhoid fever. There was no death in the study. 287 patients had blood culture confirmed typhoid fever, 145 patients received gatifloxacin and 142 patients received azithromycin. The median FCT was 106 hours in both treatment arms (95% Confidence Interval [CI]; 94-118 hours for gatifloxacin versus 88-112 hours for azithromycin), (logrank test p = 0.984, HR [95% CI] = 1.0 [0.80-1.26]). Overall treatment failure occurred in 13/145 (9%) patients in the gatifloxacin group and 13/140 (9.3%) patients in the azithromycin group, (logrank test p = 0.854, HR [95% CI] = 0.93 [0.43-2.0]). 96% (254/263) of the Salmonella enterica serovar Typhi isolates were resistant to nalidixic acid and 58% (153/263) were multidrug resistant.
                Both antibiotics showed an excellent efficacy and safety profile. Both gatifloxacin and azithromycin can be recommended for the treatment of typhoid fever particularly in regions with high rates of multidrug and nalidixic acid resistance. The cost of a 7-day treatment course of gatifloxacin is approximately one third of the cost of azithromycin in Vietnam.
                Controlled-Trials.com ISRCTN67946944. In recent years, multiresistant strains of Salmonella typhi have emerged in many tropical countries. These strains remain highly sensitive to the fluoroquinolone antibiotics, although use of these drugs by children is considered contraindicated because of their reported toxicity in the cartilage of experimental animals. In a paired, open, randomized study during an epidemic of multidrug-resistant typhoid in southern Vietnam, two short-course ofloxacin regimens (15 mg/kg daily for 3 days and 10 mg/kg daily for 5 days) were compared for the treatment of uncomplicated typhoid fever. Of 438 patients enrolled (of whom 286 were < or = 14 years old), 228 had blood cultures positive for Salmonella species (S. typhi, 207; S. paratyphi A, 19; and S. choleraesuis, 2). There was one treatment failure in a patient who took only one dose of ofloxacin. Otherwise, both regimens were completely effective; there were no proven carriers, and there was no evidence of toxicity, particularly in children. A 3-day course of ofloxacin proved to be safe and highly effective in the treatment of uncomplicated, multidrug-resistant typhoid fever. To compare the efficacy and safety of single-dose and 3-day fluoroquinolone treatment of uncomplicated urinary tract infection (UTI).
                Adult women with acute uncomplicated UTI were randomized to receive either a single dose of gatifloxacin (400 mg), 3 days of gatifloxacin (200 mg daily), or 3 days of ciprofloxacin (100 mg twice daily). Patients were assessed at four points during the study: before treatment (within 48 hours before the initiation of the study medication), at the end of treatment (by telephone contact on day 3), and twice after treatment completion (5 to 9 days after treatment [test-of-cure visit] and 29 to 42 days after treatment [only patients with a bacteriologic response of eradication at the test-of-cure visit]).
                The bacterial eradication rate for the single-dose gatifloxacin, 3-day gatifloxacin, and 3-day ciprofloxacin groups was 90%, 95%, and 89%, respectively; the clinical efficacy rate was 93%, 95%, and 93%, respectively, for microbiologically assessable patients at the test-of-cure visit. Eradication of the most common uropathogens, including Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, was achieved with gatifloxacin and ciprofloxacin. Single-dose gatifloxacin was equivalent to 3-day ciprofloxacin in both microbiologic and clinical efficacy.
                Single-dose and 3-day gatifloxacin were microbiologically and clinically equivalent to 3-day ciprofloxacin for the treatment of acute UTI among women. Single-dose gatifloxacin may offer advantages over 3-day fluoroquinolone therapy for uncomplicated UTI by decreasing secondary use of medical resources and improving patient compliance. A randomized trial comparing ceftriaxone (3 g given parenterally per day for 7 days) to ciprofloxacin (500 mg given orally twice a day for 7 days) in the treatment of blood culture positive typhoid fever was conducted. Twenty patients were openly randomized to receive ciprofloxacin and 22 to receive ceftriaxone. The outcome was classified as clinical failure in 6 patients (27%) in the ceftriaxone group, but in none in the ciprofloxacin group (p = 0.01). The mean duration of fever was four days in the ciprofloxacin group and about five days in the ceftriaxone group (p = 0.04). In the six patients in the ceftriaxone group who experienced failure, therapy was switched to ciprofloxacin and the patients became afebrile and asymptomatic within 48 hours. Patients with resistant strains of Salmonella typhi and patients with sensitive strains responded equally well to ciprofloxacin therapy. Analysis of a subset of 12 of the multiresistant strains revealed that resistance was encoded for by a transferable 180 kilobase plasmid. Ciprofloxacin represents a useful treatment option in areas where multiresistant strains are likely to be encountered. Typhoid fever continues to be a major public health problem in tropical countries, exacerbated in recent years by the spread of multi-drug resistant strains of Salmonella typhi. Short treatment courses of fluoroquinolones are effective, and have the advantage of reduced cost and increased compliance, but the optimal length of treatment is unknown. In an open, randomized comparison, 107 adults with uncomplicated enteric fever (95 of whom had positive blood cultures for S. typhi and 5 for S. paratyphi) were treated with oral ofloxacin, 15 mg/kg/d for 2 d or 10 mg/kg/d for 3 d. Mean fever clearance times were the same in the 2 treatment groups (97 h). There were 7 treatment failures, one in the 2 d group and 6 in the 3 d group (P = 0.07). Three of the 5 patients infected with nalidixic acid resistant strains of S. typhi had treatment failures, compared with 4 of 90 with nalidixic acid sensitive isolates (P < 0.0001; relative risk 13.5, 95% confidence interval 4.1-43%). Treatment with ofloxacin for 2 or 3 d is equally effective in adults with uncomplicated enteric fever caused by nalidixic acid sensitive strains of S. typhi. The epidemiology and management of nalidixic acid resistent typhoid needs further investigation. This study measured the impact of three interventions for physicians, in order to implement guidelines for sequential therapy (intravenous to oral conversion) with fluoroquinolones.
                A Belgian university hospital with 1,065 beds. Method The first intervention consisted of the hospital-wide publication of guidelines in the local drug letter towards all prescribers. The consumption of fluoroquinolones was measured by means of an interrupted time-series (ITS) analysis 21 months before (period A) and 24 months after publication (period B). The second intervention was an educational interactive session, by infectious disease specialists, to the medical staff of orthopaedics and endocrinology. The third intervention comprised a proactive conversion programme on the abdominal surgery, gastro-enterology and plastic surgery wards, where pharmacists attached a pre-printed note with a suggestion to switch to an oral treatment every time a patient met the criteria for switching. The second and third intervention took place 6 months after the first intervention. Fluoroquinolone treatments were evaluated during a 2 month period before (group 1) and after the introduction of the second (group 2) and third (group 3) intervention.
                The monthly ratio of intravenous versus total fluoroquinolone consumption (daily defined doses per 1,000 bed days) was measured to assess the impact of the first intervention. The impact of the second and third intervention was measured in relation to the number of days that intravenous therapy continued beyond the day that the patient fulfilled the criteria for sequential therapy and the antibiotic cost.
                The ITS demonstrated a reduction of 3.3% in the ratio of intravenous versus total consumption after the publication of the guidelines (P = 0.011). In group 1, patients were treated intravenously for 4.1 days longer than necessary. This parameter decreased in group 2 to 3.5 days and in group 3 to 1.0 day (P = 0.006). The mean additional cost for longer intravenous treatment decreased from 188.0 euro in group 1, to 103.0 euro in group 2 and 44.0 euro in group 3 (P = 0.037).
                This study demonstrated that active implementation of guidelines is necessary. A proactive conversion programme by a pharmacist resulted in a reduction in the duration of the intravenous treatment, and the treatment cost. Topical steroids are first-line medication to control nasal polyposis (NP), a disease with long-term clinical course.
                The aim of this study was to evaluate the efficacy and safety of fluticasone propionate aqueous nasal spray (FPANS) 200 microg twice a day (bd) after 1 month of treatment, and to compare FPANS 200 microg bd and FPANS 200 microg once a day (od) in maintenance and long-term treatment.
                Double-blind, placebo-controlled, 8-month study with three treatment periods (1-month acute period followed with 1-month maintenance period and 6-month follow-up period) was carried out. Group 1 received FPANS 200 microg bd, during acute, maintenance and follow-up periods, Group 2 received FPANS 200 microg bd during acute period and FPANS 200 microg od during maintenance and follow-up periods, and Group 3 received placebo during acute and maintenance periods and FPANS 200 microg bd during follow-up period. Endpoints were change from baseline in clinic peak nasal inspiratory flow (PNIF), domiciliary evening PNIF, intensity of symptoms and polyposis grade.
                After acute period and maintenance periods, FPANS 200 microg bd was significantly more effective than placebo on all endpoints and more effective than FPANS 200 microg od after 1-month maintenance period on clinic PNIF, evening PNIF, obstruction, percentage of days with no sense of smell and percentage of nights with no disturbances. The two doses were similar on other endpoints. After the 6-month follow-up period, there was no difference between the two doses of FPANS at all efficacy endpoints. The safety profile of FPANS did not highlight any new or unanticipated adverse events.
                The study demonstrated the efficacy of FPANS 200 microg bd in acute treatment and FPANS 200 microg od as a sufficient dose to maintain a long-term efficacy in the treatment for NP. Topical glucocorticoids are the medical treatment of choice in a majority of patients suffering from nasal polyposis. Fluticasone propionate is a fluorinated steroid reported to be highly effective when used topically in the nose for seasonal and perennial allergic and nonallergic rhinitis.
                To evaluate the efficacy and tolerability of intranasal fluticasone propionate in the treatment of long-standing polyposis.
                Fifty-five patients with long-standing nasal polyposis were treated over a 26-week period with fluticasone propionate aqueous nasal spray 200 micrograms bid, beclomethasone dipropionate aqueous nasal spray 200 micrograms bid or placebo, administered intranasally in an aqueous spray in a double-blind, placebo-controlled parallel-group design at a single center. The primary efficacy endpoint was the physicians' assessment of symptoms and polyp score. Peak nasal inspiratory flow was performed twice daily and on every visit to evaluate the effect of the corticosteroids on nasal air flow.
                A significant difference in the primary efficacy endpoint between fluticasone propionate aqueous nasal spray and beclomethasone dipropionate aqueous nasal spray compared with placebo was seen after 14 weeks of treatment. This was further verified by the peak nasal inspiratory flow results. There was some evidence of earlier onset in the fluticasone propionate aqueous nasal spray group compared with the beclomethasone dipropionate aqueous nasal spray group after 4 weeks in terms of the primary efficacy endpoint. From the daily record cards patients receiving fluticasone propionate aqueous nasal spray had a significantly higher percentage of days on which they required no rescue medication (P < .009) and a higher percentage of days with an overall nasal blockage score on waking of < 2 (P < .013) when compared with placebo-treated patients. No other statistically significant results were found between the two active compounds.
                Fluticasone propionate aqueous nasal spray 200 micrograms bid and beclomethasone dipropionate aqueous nasal spray 200 micrograms bid are effective in treating the symptoms of nasal polyps, with some evidence that fluticasone propionate aqueous nasal spray has a faster onset of action and is tolerated at least as well as beclomethasone dipropionate aqueous nasal spray at the same dose. Current treatment for pulmonary tuberculosis (TB) might be shortened by the incorporation of fluoroquinolones (FQs).
                A Phase II study aimed to assess the sterilising activities of three novel regimens containing FQs before a Phase III trial of a 4-month regimen containing gatifloxacin (GFX).
                A total of 217 newly diagnosed smear-positive patients were randomly allocated to one of four regimens: isoniazid (INH), pyrazinamide and rifampicin (RMP) with either ethambutol, GFX, moxifloxacin (MFX) or ofloxacin (OFX) for 2 months. At the end of the study, RMP and INH were given for 4 months. The rates of elimination of Mycobacterium tuberculosis were compared in the regimens using non-linear mixed effects modelling of the serial sputum colony counts (SSCC) during the first 8 weeks.
                After adjustment for covariates, MFX substitution appeared superior during the early phase of a bi-exponential fall in colony counts, but significant and similar acceleration of bacillary elimination during the late phase occurred with both GFX and MFX (P = 0.002). Substitution of OFX had no effect. These findings were supported by estimates of time to conversion, using Cox regression, but there were no significant differences in proportions culture-negative at 8 weeks.
                GFX and MFX improve the sterilising activity of regimens and might shorten treatment; their progression into Phase III trials therefore seems warranted. An open, randomized clinical study was carried out to compare the clinical efficacy and safety of pefloxacin with that of chloramphenicol in the treatment of typhoid fever. Sixty hospitalized patients (40 men and 20 women, aged from 17 to 64 years), affected by severe proven typhoid sepsis, were randomly assigned to treatment with pefloxacin at a daily dose of 1,200 mg for 15 days (Group A) or with chloramphenicol at a daily dose of 2 g for 15 days (Group B). The two groups of patients were statistically homogeneous regarding both age and sex and all patients were followed for 30 days after the end of therapy. In Group A all the patients completely recovered from infection and all the isolated strains of Salmonella typhi were eradicated by pefloxacin treatment. In Group B two patients had a relapse, two patients became chronic enteric carriers of S. typhi and only 26 patients recovered from infection with complete eradication of the pathogen. The results indicate that pefloxacin is as active as chloramphenicol in the therapy of typhoid fever and that pefloxacin could be a valid antibacterial agent to be used together with appropriate hygienic measures for an eradication program of typhoid fever in the endemic countries. Pefloxacin, which has been shown to have a high in vitro activity against Salmonella spp., was compared to cotrimoxazole in the treatment of typhoid fever in adults. In a prospective, randomized trial, 42 patients with bacteriologically documented typhoid fever received either 400 mg pefloxacin b.i.d. or 160/800 mg cotrimoxazole b.i.d. Duration of treatment was 14 days in both groups. All patients were cured without experiencing a relapse or becoming a salmonella carrier. Apyrexia and resolution of digestive and neurological symptoms were obtained in a significantly shorter time with pefloxacin than with cotrimoxazole. Pefloxacin was well tolerated and more effective than cotrimoxazole in the treatment of typhoid fever. Few reports are available on the treatment of patients with Waldenström macroglobulinemia (WM) and primary or secondary resistance to alkylating-agent-based regimens. From December 1993 through December 1997, 92 patients with WM resistant to first-line therapy (42) or with first relapse (50) after alkylating-agent therapy were randomly assigned to receive fludarabine (25 mg/m(2) of body-surface area on days 1-5) or cyclophosphamide, doxorubicin (Adriamycin), and prednisone (CAP; 750 mg/m(2) cyclophosphamide and 25 mg/m(2) doxorubicin on day 1 and 40 mg/m(2) prednisone on days 1-5). The first end point evaluated was the response rate after 6 treatment courses. Forty-five patients received CAP and 45 received fludarabine. Two patients died before the first course of chemotherapy. No statistical differences were observed between the 2 treatment arms with respect to hematologic toxicity or infections. Mucositis and alopecia occurred significantly more often in patients treated with CAP. Partial responses were obtained in 14 patients (30%) treated with fludarabine and 5 patients (11%) treated with CAP (P =.019). Responses were more durable in patients treated with fludarabine (19 months versus 3 months), and the event-free survival rate was significantly higher in this group (P <.01). Forty-four patients died, 22 in the fludarabine group and 22 in the CAP group. There was no statistical difference in the median overall survival time in the 2 study arms. Fludarabine was thus more active than CAP in salvage therapy of WM and should be tested as first-line therapy in a randomized comparison with alkylating agents. We aimed to investigate whether gatifloxacin, a new generation and affordable fluoroquinolone, is better than chloramphenicol for the treatment of uncomplicated enteric fever in children and adults.
                We did an open-label randomised superiority trial at Patan Hospital, Kathmandu, Nepal, to investigate whether gatifloxacin is more effective than chloramphenicol for treating uncomplicated enteric fever. Children and adults clinically diagnosed with enteric fever received either gatifloxacin (10 mg/kg) once a day for 7 days, or chloramphenicol (75 mg/kg per day) in four divided doses for 14 days. Patients were randomly allocated treatment (1:1) in blocks of 50, without stratification. Allocations were placed in sealed envelopes opened by the study physician once a patient was enrolled into the trial. Masking was not possible because of the different formulations and ways of giving the two drugs. The primary outcome measure was treatment failure, which consisted of at least one of the following: persistent fever at day 10, need for rescue treatment, microbiological failure, relapse until day 31, and enteric-fever-related complications. The primary outcome was assessed in all patients randomly allocated treatment and reported separately for culture-positive patients and for all patients. Secondary outcome measures were fever clearance time, late relapse, and faecal carriage. The trial is registered on controlled-trials.com, number ISRCTN 53258327.
                844 patients with a median age of 16 (IQR 9-22) years were enrolled in the trial and randomly allocated a treatment. 352 patients had blood-culture-confirmed enteric fever: 175 were treated with chloramphenicol and 177 with gatifloxacin. 14 patients had treatment failure in the chloramphenicol group, compared with 12 in the gatifloxacin group (hazard ratio [HR] of time to failure 0·86, 95% CI 0·40-1·86, p=0·70). The median time to fever clearance was 3·95 days (95% CI 3·68-4·68) in the chloramphenicol group and 3·90 days (3·58-4·27) in the gatifloxacin group (HR 1·06, 0·86-1·32, p=0·59). At 1 month only, three of 148 patients were stool-culture positive in the chloramphenicol group and none in the gatifloxacin group. At the end of 3 months only one person had a positive stool culture in the chloramphenicol group. There were no other positive stool cultures even at the end of 6 months. Late relapses were noted in three of 175 patients in the culture-confirmed chloramphenicol group and two of 177 in the gatifloxacin group. There were no culture-positive relapses after day 62. 99 patients (24%) experienced 168 adverse events in the chloramphenicol group and 59 (14%) experienced 73 events in the gatifloxacin group.
                Although no more efficacious than chloramphenicol, gatifloxacin should be the preferred treatment for enteric fever in developing countries because of its shorter treatment duration and fewer adverse events.
                Wellcome Trust.
                Copyright © 2011 Elsevier Ltd. All rights reserved. The use of fluoroquinolones as prophylaxis for bacterial infections in patients with chemotherapy induced neutropenia is debatable. The present study was conducted to assess the prophylactic efficacy of fluoroquinolones in adult neutropenic patients with hematologic malignancies.
                For the period 1994 through 2000 a prospective, randomized trial was conducted at the University Clinic of Hematology (Medical University, Plovdiv). Two groups of patients were included--experimental group, consisting of 36 patients with 41 granulocytopenic episodes and a control group of 34 patients with 41 granulocytopenic episodes. Non parametrical and psi methods were used for statistical analysis. Kaplan-Meier test was employed to determine patients' survival rate. Comparison of survival rates between the two groups was performed using the log-rank test.
                A statistically significant difference between the two groups was found in the number of infection-free neutropenic episodes (P < 0.001), in infection-related mortality rate (p = 0.001) and mortality rate within 1 month of the onset of infection (p < 0.001). Difference in long term survival rates was not statistically significant (p > 0.05).
                Prophylaxis with fluoroquinolones reduced the occurrence of infection in adult neutropenic patients without affecting the long-term survival. Moreover, it is especially beneficial for patients with severe neutropenia and during the active phase of the disease. The efficacy and safety of three oral fluoroquinolones (lomefloxacin, levofloxacin, and ciprofloxacin) for the treatment of chronic osteomyelitis were analyzed. Twenty-seven patients had documented infections with quinolone-sensitive organisms and received either lomefloxacin, levofloxacin, or ciprofloxacin. Levofloxacin was effective therapy for 9 of 15 (60%) patients. Lomefloxacin was effective therapy for five of seven (71%) patients, and ciprofloxacin was effective therapy for two of five patients (40%). Average follow-up was 11.8 months for patients who completed the course of therapy, and the average duration of therapy was 60.6 days. Gram-positive bacteria were isolated from 18 patients, and 11 patients were cured. Oral fluoroquinolones can be safe, effective therapy if they are given for a prolonged course as treatment for infections caused by susceptible gram-positive as well as gram-negative organisms and in combination with adequate surgical debridement. To investigate the effect of intranasal corticosteroids in the treatment of polyps in patients with severe polyposis listed for surgical treatment and to determine the treatment effect on the progression of the disease.
                A double-blind, randomized, parallel-group, placebo-controlled, 12-week study at a single center.
                A tertiary referral center in London, England.
                Thirty-four patients with severe polyposis listed for endoscopic surgical treatment.
                By random allocation, fluticasone propionate aqueous nasal spray (FPANS), 200 microg twice a day; beclomethasone dipropionate aqueous nasal spray, 200 microg twice a day; or placebo nasal spray twice a day was administered. Patients received 2 actuations to each nostril in the morning and in the evening.
                Efficacy end points were the need for polypectomy at the end of treatment, the results of acoustic rhinometry, the polyp score, the peak nasal inspiratory flow rate, and an assessment of symptoms.
                The polyp score was significantly decreased in the FPANS-treated group (P < or = .01). The nasal cavity volume was significantly increased in both the FPANS-treated group and the group receiving beclomethasone compared with placebo (P < or = .01) at the end of treatment. The percentage change in the mean morning peak nasal inspiratory flow rate was greater in the FPANS-treated group, with a significant effect observed at week 2 (P = .01). Nasal blockage was significantly decreased in both active groups compared with the group receiving placebo. No significant difference was observed between the treatment groups in the number of patients requiring polypectomy.
                Fluticasone and beclomethasone aqueous nasal sprays are effective in treating the symptoms of severe nasal polyps. There was some evidence that the group treated with FPANS responded more quickly to intervention and that the magnitude of the response was greater than in the group receiving beclomethasone. The inhaled corticosteroid, fluticasone propionate, was compared with the oral bronchodilator theophylline in the maintenance treatment of asthma.
                The objective of the present study was to compare the efficacy and safety of twice-daily inhaled fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, with that of theophylline in the maintenance treatment of mild-to-moderate asthma.
                In this randomized, double-blind, placebo-controlled, parallel-group study, 353 adult and adolescent patients with asthma inadequately controlled with inhaled beta-agonist therapy alone received fluticasone propionate, 50 micrograms, or fluticasone propionate, 100 micrograms, by metered-dose inhaler; theophylline capsules; or placebo twice daily for 12 weeks. Only inhaled albuterol was permitted as needed for acute symptoms.
                Both fluticasone propionate groups had a significantly greater probability of remaining in the study (ie, meeting asthma stability criteria) than did either the theophylline or placebo group (P < or = .008); 39% and 51% in the theophylline and placebo groups, respectively, were withdrawn due to lack of treatment efficacy compared with 14% and 21% in the fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, groups. Both fluticasone propionate groups experienced significantly greater improvement in FEV1 and PEF compared with patients in the theophylline or placebo group (P < or = .004). The incidence of potentially drug-related adverse events was significantly greater in the theophylline group (25%) than in the placebo group (11%) (P = .031), while there were no differences between placebo and fluticasone propionate, 50 micrograms, (18%) or fluticasone propionate 100 micrograms, (22%).
                Twice daily treatment with inhaled fluticasone propionate 50 micrograms or 100 micrograms was significantly more effective than theophylline in the treatment of mild-to-moderate asthma. The efficacy and safety of a fixed-dose combination of atovaquone and proguanil hydrochloride (Malarone) were compared with chloroquine or pyrimethamine/sulfadoxine in patients with acute falciparum malaria in northern Peru. Patients were initially randomized to receive 1,000 mg atovaquone and 400 mg proguanil hydrochloride daily for 3 days (n=15) or 1,500 mg chloroquine (base) over a 3 day period (n=14) (phase 1). The cure rate with chloroquine was lower than expected and patients were subsequently randomized to receive a single dose of 75 mg pyrimethamine and 1,500 mg sulfadoxine (n=9) or atovaquone/proguanil as before (n=5) (phase 2). In phase 1, atovaquone/proguanil was significantly more effective than chloroquine (cure rate 100% [14/14] vs. 8% [1/13], P<0.0001). In phase 2, atovaquone/proguanil and pyrimethamine/sulfadoxine were both highly effective (cure rates 100% [5/5] and 100% [7/7]). There were no significant differences between treatment groups in parasite or fever clearance times. Adverse events were typical of malarial symptoms and did not differ significantly between groups. Overall efficacy of atovaquone/proguanil was 100% for treatment of acute falciparum malaria in a region with a high prevalence of chloroquine resistance. This double blind, parallel study compared flunisolide 2 X 25 mcg in each nostril twice daily, with placebo in the prophylaxis of nasal polyposis recurrence after surgery. The treatment lasted for 12 months. The study was conducted according to the recommendations of the Declaration of Helsinki, and the patients gave verbal consent to participate. The study was reviewed by the Norwegian Medicines Control Authority. Forty-one patients with first or recurrent polypectomy were enrolled. Thirty-seven patients completed the 12 months' period. Four patients dropped out prematurely for reasons unrelated to the test drug. Flunisolide was significantly superior to placebo in preventing recurrence of polyps during 6 to 12 months' treatment, both with respect to number (p = 0.05) and size (p = 0.03) of polyps. Nasal symptoms of sneezing and stuffiness decreased significantly for flunisolide treated patients during treatment. In the placebo group, there was a significant increase in stuffiness throughout the year. For runny nose, there was no difference between the treatments. Six flunisolide patients and 10 placebo patients reported side effects during the one year treatment, transient mild itching being the most common complaint. Three cases of secretion with bloody traces were reported. No patient withdrew for drug related reasons. In this study, flunisolide was significantly more effective than placebo in preventing recurrence of nasal polyposis during one year's treatment after polypectomy.
Generally, fluoroquinolones performed well in treating typhoid, and maybe superior to alternatives in some settings. However, we were unable to draw firm general conclusions on comparative contemporary effectiveness given that resistance changes over time, and many studies were small. Policy makers and clinicians need to consider local resistance patterns in choosing a fluoroquinolone or alternative.
There is some evidence that the newest fluoroquinolone, gatifloxacin, remains effective in some regions where resistance to older fluoroquinolones has developed. However, the different fluoroquinolones have not been compared directly in trials in these settings.