Antimicrobial resistance of Streptococcus pneumoniae and Haemophilus influenzae in Sao Paulo, Brazil from 1996 to 2000

This study was undertaken to assess the in vitro activity of several antimicrobial agents against Brazilian isolates of Streptococcus pneumoniae and Haemophilus influenzae from 1996 to 2000. The antibiotics used were penicillin, amoxicillin/clavulanic acid (A/C), ampicillin, amoxicillin, cefaclor, cefdinir, cefixime, cefprozil, ceftriaxone, cefuroxime, azithromycin, clarithromycin, erythromycin, ciprofloxacin, levofloxacin, ofloxacin, chloramphenicol, clindamycin, doxycycline and trimethoprim/sulphamethoxazole (T/S). MICs were determined by the National Committee for Clinical Laboratory Standards (NCCLS) method and interpreted using NCCLS and PK/PD breakpoints. For S. pneumoniae 80.0% were penicillin susceptible, 18.3% intermediate, 1.7% resistant; most active agents were amoxicillin, A/C, ceftriaxone and levofloxacin; T/S was the least active agent. Beta-lactamase was produced by 13.7% of H. influenzae. All were susceptible to A/C, cefdinir, cefixime, ceftriaxone and quinolones. The least active agents were T/S and macrolides.     

Azithromycin. A pharmacoeconomic review of its use as a single-dose regimen in the treatment of uncomplicated urogenital Chlamydia trachomatis infections in women

In women, Chlamydia trachomatis infection often occurs in the urethra or cervix, with up to 70% of infections associated with few or no symptoms. Inadequate treatment may lead to infection of the upper genital tract and subsequent pelvic inflammatory disease (PID) in 10 to 40% of patients. PID causes an increased relative risk of ectopic pregnancy of 2.5 to 7.9 and PID may also lead to tubal infertility in about 17% of patients. 60% of infants born of mothers with C. trachomatis infection may become infected, leading to conjunctivitis in 23% and pneumonia in 21%. All of these sequelae of C. trachomatis infection may require in- or outpatient treatment. With > 4 million infections estimated to occur each year in the US, C. trachomatis is one of the most common and costly of the sexually transmitted pathogens. Treatment options for uncomplicated C. trachomatis infections in nonpregnant women include single-dose azithromycin 1000 mg or doxycycline 100 mg twice daily for 7 days orally. In clinical trials, the bacteriological cure rate of single dose azithromycin 1000 mg (95 to 100%) was similar to that of oral doxycycline 200 mg/day for 7 days (88 to 100%) in nonpregnant women. Azithromycin was at least as well tolerated as doxycycline and was associated with mainly mild gastrointestinal adverse effects including diarrhoea, nausea and abdominal pain. Pharmacoeconomic analyses have sought to determine if the 2.7- to 12-fold higher acquisition costs of azithromycin in comparison with doxycycline are offset by its simple single-dose regimen which is likely to aid patient compliance and so optimise drug efficacy. All analyses were retrospective cost-effectiveness decision-tree models and mainly considered direct costs. All models incorporated an estimate of noncompliance with doxycycline and its influence on efficacy. For the treatment of confirmed C. trachomatis infection, azithromycin saved around $US1200 per major outcome avoided (1993 values; third-party payer perspective in the US) or US$3502 per case of PID avoided (1993 values; US healthcare system perspective) compared with doxycycline. If infection was treated empirically, azithromycin was more costly than doxycycline by $US792 (1993 values), but the result was sensitive to changes of some parameters of the model. Azithromycin was more costly than doxycycline from the perspective of a public health clinic which paid for the treatment of initial infection and acute sequelae only. Thus, pharmacoeconomic data from the US support the use of azithromycin in the treatment of nonpregnant women with confirmed C. trachomatis urogenital infections from the perspective of the healthcare system or third-party payer; however, from the perspective of a public clinic, doxycycline is the less costly option. Decreases in doxycycline compliance or azithromycin acquisition cost are factors that favour azithromycin.     

Treatment of sexually transmitted bacterial diseases in pregnant women

Testing for and treating sexually transmitted diseases (STDs) in pregnant women deserves special attention. Treatment possibilities are limited because of potential risks for the developing fetus, and because effects can differ in pregnant compared with non-pregnant women, re-infection may be missed because of the intrinsic delicacy of contact-tracing during pregnancy and because pregnant women are more reluctant to take the prescribed medication in its full dose, if at all. However, the devastating effects of some of these genital infections far outweigh any potential adverse effects of treatment. Although active syphilis has become a rarity in most Western countries, it is still prevalent in South America, Africa and South-East Asia. Benzathine benzylpenicillin (2.4 million units once or, safer, twice 7 days apart) is the treatment of choice, although patients with syphilis of longer standing require 3 weekly injections as well as extensive investigation into whether there has been any damage due to tertiary syphilis. Despite declining rates of gonorrhea, the relative rate of penicillinase-producing strains is increasing, especially in South-East Asia. The recommended treatment is intramuscular ceftriaxone (125 or 250 mg) or oral cefixime 400 mg. Despite good safety records after accidental use, fluoroquinolones are contraindicated during pregnancy. An alternative to a fluoroquinolone in pregnant women with combined gonorrhea and chlamydial infection is oral azithromycin 1 or 2 g. Azithromycin as a single 1 g dose is also preferable to a 7 day course of erythromycin 500 mg 4 times a day for patients with chlamydial infection. Eradication of Haemophilus ducreyi in patients with chancroid can also be achieved with these regimens or intramuscular ceftriaxone 250 mg. Trichomonas vaginalis, which is often seen as a co-infection, has been linked to an increased risk of preterm birth. Patients infected with this parasite should therefore received metronidazole 500 mg twice daily for 7 days as earlier fears of teratogenesis in humans have not been confirmed by recent data. Bacterial vaginosis is also associated with preterm delivery in certain risk groups, such as women with a history of preterm birth or of low maternal weight. Such an association is yet to be convincingly proven in other women. The current advice is to treat only women diagnosed with bacterial vaginosis who also present other risk factors for preterm delivery. The treatment of choice is oral metronidazole 1 g/day for 5 days. The possible reduction of preterm birth by vaginally applied metronidazole or clindamycin is still under investigation. In general, both test of cure and re-testing after several weeks are advisable in most pregnant patients with STDs, because partner notification and treatment are likely to be less efficient than outside pregnancy and the impact of inadequately treated or recurrent disease is greater because of the added risk to the fetus. Every diagnosis of an STD warrants a full screen for concomitant genital disease. Most ulcerative genital infections, as well as abnormal vaginal flora and bacterial vaginosis, increase the sexual transmission efficiency of HIV, necessitating even more stringent screening for and treating of STD during pregnancy.     

洛美沙星治疗淋病临床疗效对比观察

观察了国产洛美沙星与氧氟沙星随机对照治疗无合并症淋病１０１例的临床疗效及不良反应。洛美沙星组５８例，氧氟沙星组４３例。男性病人８７例服用洛美沙星或氧氟沙星２００ｍｇ，每日２次，２天；女性病人１４例服４００ｍｇ，每日２次，２天。两药临床治愈率分别为９３．１％（５４／５８）和９０．７％（３９／４３），无显著性差异（Ｐ＞０．０５）。细菌清除率分别为９６．６％（５６／５８）和９３．０２％（４０／４３）。其不良反应发生率分别为１．７％（１／５８）和２．３％（１／４３），反应轻微。洛美沙星、氧氟沙星、环丙沙星、头孢曲松、青霉素和大观霉素对５６株淋球菌的ＭＩＣ＿（５０）／ＭＩＣ＿（９０）（ｍｇ／Ｌ）为０．０６／０．２５、０．０６／０．１２５、０．０６／０．１２５、０．０６／０．２５、０．５／１．０和１６／３２。     

Cost-minimisation analysis of sequential treatment with ofloxacin or ciprofloxacin in hospitalised patients

This study evaluated the cost of sequential treatment with once-daily ofloxacin or twice-daily ciprofloxacin in 474 hospitalised patients in different countries. The patients were treated intravenously for at least 3 days, then orally for 7 to 10 days or for 3 days beyond the disappearance of infection-related symptoms. The overall clinical cure rate (86.8% with ofloxacin and 89.6% with ciprofloxacin) and the overall bacteriological response rate (89.9 and 89.0%, respectively) were similar, and a cost-minimisation analysis was conducted. The acquisition costs for ofloxacin and ciprofloxacin in Greece, Israel, Slovenia and Turkey were used and converted to Deutschmarks (DM), and the costs of administration were analysed for each hospital. The different cost categories for oral and intravenous (IV) treatment (e.g. antimicrobial acquisition, drug monitoring, drug delivery costs) were used to identify any differences. The total costs per patient varied between the countries involved, but were higher for ciprofloxacin (ofloxacin: DM239 to DM724; ciprofloxacin: DM540 to DM976). In a sensitivity analysis using identical daily acquisition costs for the 2 fluoroquinolones, the total cost of treatment was higher for ciprofloxacin, as a result of the lower cost of administration of ofloxacin in the once-daily regimen. Continuing IV therapy would be approximately 50% more expensive than switching to oral administration; however, whenever possible, both drugs can be switched from IV to oral treatment.     

Levofloxacin: a review of its use in the treatment of bacterial infections in the United States

Levofloxacin (Levaquin) is a fluoroquinolone antibacterial agent with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and atypical respiratory pathogens. It is active against both penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae. The prevalence of S. pneumoniae resistance to levofloxacin is <1% overall in the US.A number of randomised comparative trials in the US have demonstrated the efficacy of levofloxacin in the treatment of infections of the respiratory tract, genitourinary tract, skin and skin structures. Sequential intravenous to oral levofloxacin 750mg once daily for 7-14 days was as effective in the treatment of nosocomial pneumonia as intravenous imipenem/cilastatin 500-1000mg every 6-8 hours followed by oral ciprofloxacin 750mg twice daily in one study. In patients with mild to severe community-acquired pneumonia (CAP), intravenous and/or oral levofloxacin 500mg once daily for 7-14 days achieved clinical and bacteriological response rates similar to those with comparator agents, including amoxicillin/clavulanic acid, clarithromycin, azithromycin, ceftriaxone and/or cefuroxime axetil and gatifloxacin. A recent study indicates that intravenous or oral levofloxacin 750mg once daily for 5 days is as effective as 500mg once daily for 10 days, in the treatment of mild to severe CAP. Exacerbations of chronic bronchitis and acute maxillary sinusitis respond well to treatment with oral levofloxacin 500mg once daily for 7 and 10-14 days, respectively.Oral levofloxacin was as effective as ofloxacin in uncomplicated urinary tract infections and ciprofloxacin or lomefloxacin in complicated urinary tract infections. In men with chronic bacterial prostatitis treated for 28 days, oral levofloxacin 500mg once daily achieved similar clinical and bacteriological response rates to oral ciprofloxacin 500mg twice daily. Uncomplicated skin infections responded well to oral levofloxacin 500mg once daily for 7-10 days, while in complicated skin infections intravenous and/or oral levofloxacin 750mg for 7-14 days was at least as effective as intravenous ticarcillin/clavulanic acid (+/- switch to oral amoxicillin/clavulanic acid) administered for the same duration.Levofloxacin is generally well tolerated, with the most frequently reported adverse events being nausea and diarrhoea; in comparison with some other quinolones it has a low photosensitising potential and clinically significant cardiac and hepatic adverse events are rare. CONCLUSION: Levofloxacin is a broad-spectrum antibacterial agent with activity against a range of Gram-positive and Gram-negative bacteria and atypical organisms. It provides clinical and bacteriological efficacy in a range of infections, including those caused by both penicillin-susceptible and -resistant strains of S. pneumoniae. Levofloxacin is well tolerated, and is associated with few of the phototoxic, cardiac or hepatic adverse events seen with some other quinolones. It also has a pharmacokinetic profile that is compatible with once-daily administration and allows for sequential intravenous to oral therapy. The recent approvals in the US for use in the treatment of nosocomial pneumonia and chronic bacterial prostatitis, and the introduction of a short-course, high-dose regimen for use in CAP, further extend the role of levofloxacin in treating bacterial infections.     

Cefpodoxime proxetil. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential.

Cefpodoxime proxetil is an orally administered prodrug which is absorbed and de-esterified by the intestinal mucosa to release the third generation cephalosporin, cefpodoxime. Cefpodoxime is stable towards the most commonly found plasmid-mediated beta-lactamases and the drug has a broad spectrum of antibacterial activity encompassing both Gram-negative and Gram-positive bacteria, rendering it a possible option for empirical use in a wide range of community acquired infections in both adult and paediatric patients. The extended plasma half-life of cefpodoxime (1.9 to 3.7 h) permits twice daily administration. In comparative trials, twice daily cefpodoxime proxetil (dose equivalent cefpodoxime 100 to 400 mg) was as effective as a 3- to 4-times daily regimen of phenoxymethylpenicillin in pharyngotonsillitis, as well as thrice daily amoxicillin (with or without clavulanic acid) or cefaclor against infections of the ear, the upper and lower respiratory tract, the urinary tract and those of the skin and soft tissues. The latter reflects the enhanced antistaphylococcal activity of cefpodoxime, which distinguishes it from other orally active third generation cephalosporins such as cefixime. Most notably, an oral regimen of cefpodoxime proxetil was as efficacious as parenterally administered ceftriaxone for the treatment of bronchopneumonia in hospitalised patients at risk due to the presence of underlying diseases, addictions or advancing age. A single oral dose of cefpodoxime was also as efficacious as ceftriaxone in uncomplicated anogenital gonococcal infections. Cefpodoxime proxetil is generally well tolerated, with mild to moderate gastrointestinal disturbances occurring in 4 to 15% of patients treated with therapeutic doses. Thus, a convenient twice daily oral regimen of cefpodoxime proxetil can be prescribed as an effective alternative to established beta-lactam therapies in the empirical outpatient treatment of infections of the respiratory and urinary tracts as well as those of the skin and soft tissues.     

Antibacterial therapy of neurosyphilis: lack of impact of new therapies

Neurosyphilis is caused by the spirochete Treponema pallidum. These organisms divide slowly, requiring long exposure to antibacterials for treatment success. In order for an antibacterial to be effective in the therapy of neurosyphilis, it must achieve treponemicidal concentrations in the CSF, have a long half-life and be given in a treatment regimen that favours compliance. Penicillin was first introduced for the treatment of syphilis in 1943, and despite interest in the use of amoxicillin, erythromycin, tetracycline, doxycycline, ceftriaxone and azithromycin, penicillin remains the only recommended antibacterial agent for neurosyphilis.     

Tolerability of 3-day, once-daily azithromycin suspension versus standard treatments for community-acquired paediatric infectious diseases.

Tolerability of azithromycin oral suspension, 10 mg/kg once daily for 3 days, was assessed in paediatric patients (< or = 18 years) with respiratory or skin and soft-tissue infections. Of 2425 patients evaluated, 1213 received azithromycin and 1212 received standard regimens of amoxycillin/clavulanic acid, cefaclor, cefixime, ceftriaxone, clarithromycin, erythromycin, or penicillin V. The incidence of treatment-related adverse events was significantly lower in patients receiving azithromycin than comparators (7.9 vs. 11.5%, P=0.003), while discontinuation rates were similar (1.0 and 1.1%, respectively). Significantly fewer gastrointestinal events were recorded for azithromycin than comparators (6.5 vs. 9.9%, P=0.002), and their duration was significantly shorter (mean 2.3 vs. 5.0 days, P=0.0001). Azithromycin paediatric oral suspension is well tolerated and associated with significantly fewer adverse events than comparators.     

Quinolones in the treatment of gonorrhoea and Chlamydia trachomatis infections

The results of two therapeutic trials in female patients with uncomplicated urogenital gonorrhoea (A) and in male patients with uncomplicated urethral gonorrhoea (B) treated with either 200 mg and 400 mg enoxacin orally, of one therapeutic trial in male patients with uncomplicated urogenital gonorrhoea treated with either 250 mg or 500 mg ciprofloxacin orally (C) and of one therapeutic trial in male patients with non-gonococcal urethritis (NGU) treated with ciprofloxacin 1 g daily during seven days (D) are presented and compared with the results of other investigators. The cure rate in study A was 100% (n=40) in the 400 mg group and 95.7% (n=46) in the 200 mg group. The cure rate in study B was 92% (n=78) in the 400 mg group and 90% (n=77) in the 200 mg group. In both studies no antichlamydial effect of enoxacin was observed. The cure rates in study C were 100% with 250 and 500 mg. An antichlamydial effect seemed to be present. In studies A, B and C side effects were minor and rare and were mainly nausea and headache. In study D (100 patients suffering from NGU) disappearance ofChlamydia trachomatis andUreaplasma urealyticum one day after the end of treatment was observed in 29 of 32 (91 %) and 28 of 32 (88%) cases, respectively. Pyuria disappeared in 44% and 74% of the patients showed clinical cure. However, two weeks after the end of treatmentChlamydia trachomatis andUreaplasma urealyticum were observed in respectively six and eight cases. In 30% pyuria was still absent. Side effects were only minor. In conclusion, ciprofloxacin can be considered a drug of choice in uncomplicated urethral gonorrhoea. It may also be of value in NGU and in mixed gonococcal and chlamydial infections.     

In vitro activity of GAR-936 against Chlamydia pneumoniae and Chlamydia trachomatis

We evaluated the in vitro activity of GAR-936, a novel glycylcycline antibiotic, against ten isolates of Chlamydia pneumoniae and five strains of C. trachomatis. Susceptibility testing was done in HEp-2 cells. The MIC90s and MBC90s of GAR-936, doxycycline, ofloxacin and clarithromycin against C. pneumoniae were 0.125, 0.25, 0.25 and 0.06 mg/l, respectively. The MICs and MBCs of GAR-936, doxycycline, ofloxacin and clarithromycin against C. trachomatis were 0.03-0.125, 0.25, 0.25-0.5 and 0.06 mg/l, respectively. GAR-936 had excellent activity against both chlamydial species and may have a potential role in the treatment of human chlamydial infection.     

我国梅毒治疗及梅毒耐药现况

近年来,我国梅毒发病率增长迅速,而有效治疗梅毒对切断传染源、防止梅毒传播和控制其发病率至关重要.注射用青霉素是各期梅毒的首选治疗药物;对青霉素过敏患者的替代治疗药物包括头孢曲松、多西环素、四环素、红霉素和阿奇霉素等.我国报道梅毒苍白螺旋体多对阿奇霉素耐药,临床医生必须密切关注耐药的发生并慎用此药.     

Pharmacodynamics of ceftriaxone and cefixime against community-acquired respiratory tract pathogens

Over the last decade or so there has been a growing interest in routes of antimicrobial administration other than by the conventional intravenous route for institutionalized patients and for some outpatients. Both oral (PO) and intramuscular (IM) routes of administration are less costly than giving antimicrobial agents by vein (IV). In addition, fewer complications such as catheter-related sepsis and phlebitis are associated with non-IV routes of administration. Furthermore, a reduced-dosage, reduced-volume IM administration of ceftriaxone may provide a tolerable route of administration and equivalent bactericidal activities compared with higher dose IV ceftriaxone. The purpose of this study was to determine the time that the drug concentration remained in excess of the minimum inhibitory concentration (MIC) (T>MIC) and the duration of bactericidal activities of ceftriaxone one gram administered IV, ceftriaxone 250 mg given IM and cefixime 400 mg given orally against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in adult volunteers. Single doses of each agent were administered and serum concentrations were collected over the standard dosing period of 24 h for all study regimens. Ceftriaxone, regardless of route of administration and dose, resulted in bactericidal activities and T>MIC for 100% of the dosing period for S. pneumoniae, H. influenzae, and M. catarrhalis. Cefixime maintained at least 50% T>MIC and bactericidal activity against both isolates each of H. influenzae and M. catarrhalis. Against both isolates of S. pneumoniae, cefixime achieved T>MIC for at least 50% of the dosing period, but did not maintain bactericidal activity. Reduced dose ceftriaxone given IM seems to be a viable alternative to ceftriaxone IV if the pathogen, susceptibility and infection site are known. Based on T>MIC exceeding 50% of the dosing interval, cefixime would be considered an effective alternative to IV therapy against common respiratory tract pathogens. Clinical studies need to be conducted to confirm these findings.     

In vitro resistance of Bacillus anthracis Sterne to doxycycline, macrolides and quinolones

Bacillus anthracis is a potential biological warfare agent. Its ability to develop resistance to antimicrobial agents currently recommended for the treatment of anthrax infection is a major concern. B. anthracis Sterne was grown from a live veterinary vaccine and used it to test for the development of resistance after 21 sequential subcultures in sub-inhibitory concentrations of doxycycline and three quinolones (ciprofloxacin, alatrofloxacin and gatifloxacin) and 15 sequential subcultures in sub-inhibitory concentrations of three macrolides (erythromycin, azithromycin and clarithromycin). After 21 subcultures the minimal inhibitory concentrations (MICs) increased from 0.1 to 1.6 mg/l for ciprofloxacin, from 1.6 to 12.5 mg/l for alatrofloxacin, from 0.025 to 1.6 mg/l for gatifloxacin and from 0.025 to 0.1 mg/l for doxycycline. After 15 passages of sequential subculturing with macrolides, the MICs increased from 12.5 to 12.5 or 50.0 mg/l for azithromycin, from 0.2 to 1.6 or 0.4 mg/l for clarithromycin and from 6.25 to 6.25 or 50 mg/l for erythromycin. After sequential passages with a single quinolone or doxycycline, each isolate was cross-tested for resistance using the other drugs. All isolates selected for resistance to one quinolone were also resistant to the other two quinolones, but not to doxycycline. The doxycycline-resistant isolate was not resistant to any quinolone.     

Cefixime. A review of its antibacterial activity. Pharmacokinetic properties and therapeutic potential

Cefixime, previously designated FK027, FR17027 and CL284635, is an orally active cephalosporin with a broad spectrum of antibacterial activity in vitro. It is particularly active against many Enterobacteriaceae, Haemophilus influenzae. Streptococcus pyogenes, Streptococcus pneumoniae and Branhamella catarrhalis, and is resistant to hydrolysis by many beta-lactamases. Cefixime has little activity against Staphylococcus aureus and is inactive against Pseudomonas aeruginosa. Cefixime is distinguished by its 3-hour elimination half-life which permits twice daily, or in many instances once daily, administration. Comparative trials, though few, indicate that the clinical and bacteriological efficacy of cefixime 200 to 400mg daily administered as a single dose or in 2 divided doses, is comparable with that of multiple daily doses of co-trimoxazole (trimethoprim + sulphamethoxazole) or amoxycillin in acute uncomplicated urinary tract infection, with that of amoxycillin, amoxycillin/clavulanic acid and cefaclor in acute lower respiratory tract infections, and with that of amoxycillin and cefroxidine in adult patients with acute tonsillitis or pharyngitis. Several comparative trials in children with acute otitis media demonstrate the similar effectiveness of cefixime 8 mg/kg daily (in 2 divided doses, or as a single daily dose), cefaclor 20 to 40 mg/kg daily and amoxycillin 40 mg/kg daily in 3 divided doses. The most frequently reported adverse effects, diarrhoea and stool changes, are usually mild to moderate in severity, transient, and mostly occur in the first few days of treatment with cefixime. Thus, cefixime is an effective orally active cephalosporin with a relatively long elimination half-life permitting a simplified treatment regimen. It is a suitable alternative to cefaclor or amoxycillin in acute otitis media and acute upper and lower respiratory tract infections, and to amoxycillin or co-trimoxazole in acute uncomplicated urinary tract infections.     

Comparative randomized pilot study of azithromycin and doxycycline efficacy in the treatment of prostate infection caused by Chlamydia trachomatis

The study included 125 adult patients (> 18years of age) who had symptoms of chronic prostatitis and proven presence of Chlamydia trachomatis. The presence of C. trachomatis was confirmed in expressed prostatic secretion or in voided bladder urine collected immediately after prostatic massage by a DNA/RNA hybridization method and/or by isolation on McCoy culture and then by immunofluorescent typing with monoclonal antibodies. The patients were randomized in the ratio 2/1; azithromycin/doxycycline, to receive a total of 4.0 g azithromycin over 4 weeks, given as a single dose of 1 x 1000 mg weekly for 4 weeks or doxycycline 100 mg b.i.d. for 28 days. Patients' sexual partners were treated at the same time. Clinical and bacteriological efficacy was evaluated 4-6 weeks after the end of therapy. In the group of patients with chlamydial infection of the prostate, there was no significant difference between the eradication rates (azithromycin 65/82, doxycycline 33/43; P = 0.82) and the clinical cure rates (azithromycin 56/82, doxycycline 30/43; P = 0.94) of the two antimicrobials.     

Levofloxacin: an updated review of its use in the treatment of bacterial infections

Levofloxacin is the L-form of the fluoroquinolone antibacterial agent, ofloxacin. In in vitro studies, levofloxacin demonstrated a broad range of activity against Gram-positive and -negative organisms and anaerobes. The drug is more active against Gram-positive organisms than ciprofloxacin, but less active than newer fluoroquinolones such as gatifloxacin. Its activity against Streptococcus pneumoniae is unaffected by the presence of penicillin resistance. In several randomised controlled trails, 5 to 14 days' treatment with intravenous and/or oral levofloxacin proved an effective therapy for upper and lower respiratory tract infections. In patients with mild to severe community-acquired pneumonia (CAP), intravenous and/or oral levofloxacin 500mg once or twice daily was as effective as intravenous and/or oral gatifloxacin, clarithromycin, azithromycin or amoxicillin/clavulanic acid. Overall, clinical response rates with levofloxacin ranged from 86 to 95% versus 88 to 96% with comparator agents; bacteriological response rates were 88 to 95% and 86 to 98%, respectively. Sequential (intravenous +/- oral switch) therapy with levofloxacin 750mg once daily was as effective as intravenous imipenem/cilastatin (+/- oral switch to ciprofloxacin) in patients with severe nosocomial pneumonia. Generally, oral levofloxacin 250 or 500mg once daily was at least as effective as oral cefaclor, cefuroxime axetil, clarithromycin or moxifloxacin in patients with acute exacerbations of chronic bronchitis as assessed by either clinical or bacteriological response rates. This approach also provided similar efficacy to amoxicillin/ clavulanic acid or clarithromycin in patients with acute sinusitis. Sequential therapy with levofloxacin 500mg twice daily for 7 to 14 days' was as effective as intravenous imipenem/cilastatin in patients with suspected bacteraemia. Oral levofloxacin 500mg once daily for 7 to 10 days was also an effective treatment in patients with uncomplicated skin and skin structure infections, and in those with complicated urinary tract infections. A higher dosage of sequential levofloxacin 750mg once daily proved as effective as intravenous ticarcillin/clavulanic acid (+/- oral switch to amoxicillin/clavulanic acid) in the treatment of complicated skin and skin structure infections. Pharmacoeconomic studies suggest that levofloxacin may be cost-saving in comparison to conventional therapies. CONCLUSIONS: Levofloxacin continues to demonstrate good clinical efficacy in the treatment of a range of infections, including those in which S. pneumoniae is a potential pathogen. Importantly, it has efficacy in CAP similar to that of gatifloxacin and at least as good as that of the third generation cephalosporins. Extensive clinical data confirm the good tolerability profile of this agent without the phototoxicity, hepatic and cardiac events evident with some of the other newer fluoroquinolone agents. Levofloxacin therefore offers a unique combination of documented efficacy and tolerability, and provides an important option for the treatment of bacterial infections.     

Gatifloxacin 400 mg as a single shot or 200 mg once daily for 3 days is as effective as ciprofloxacin 250 mg twice daily for the treatment of patients with uncomplicated urinary tract infections

The efficacy and safety of two oral dosing regimens of gatifloxacin compared with ciprofloxacin for the treatment of acute uncomplicated lower urinary tract infection was investigated in a double-blind, randomised study, in adult female patients who received either gatifloxacin (400 mg as a single shot or 3 days of 200 mg once daily) or ciprofloxacin (250 mg given twice daily for 3 days). Bacteriological and clinical responses were assessed 7–9 days after the end of treatment (EOT), and 4–6 weeks post-treatment (end of study, EOS). One thousand one hundred and two women were treated, 741 (248 in the gatifloxacin 400 mg group, 252 in the gatifloxacin 200 mg group, and 241 in the ciprofloxacin group) presented with bacteriological proof of infection and entered the efficacy analysis. The bacteriological response per patient at EOT in the three groups were 80% (177/220) [95% CI to ciprofloxacin −8.4%; 6.4%], 83% (184/222) [95% CI to ciprofloxacin −5.9%; 8.7%] and 81% (176/216), respectively. At the follow-up assessment they were slightly lower, 75% (167/224), 79% (169/213) and 79% (171/217), respectively. The clinical responses at EOT were 81% (197/243) [95% CI to ciprofloxacin −10.2%; 3.4%], 85% (213/250) [95% CI to ciprofloxacin −5.7%; 7.2%] and 85% (201/238), respectively. At EOS they were 82% (195/239), 88% (212/241) and 86% (200/233), respectively. The eradication rates for all initial pathogens at the EOT were 90.3% in the gatifloxacin 400 mg S.D. group, 90.6% in the gatifloxacin 200 mg group, and 88.3% in the ciprofloxacin group. All treatment groups showed a similar safety profile. The incidence of treatment-related adverse events was comparable, the majority of adverse events were of mild or moderate intensity and the medications were well tolerated. Both the administration of gatifloxacin 200 mg once daily for 3 days, and gatifloxacin 400 mg as a single shot were shown to be equivalent to ciprofloxacin 250 mg twice daily for 3 days for the treatment of acute uncomplicated lower urinary tract infections.