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.     

Ertapenem: a review of its use in the treatment of bacterial infections

The Group 1, 1 beta-methyl carbapenem ertapenem (Invanz) is approved for parenteral use in patients with complicated intra-abdominal infection (cIAI), community-acquired pneumonia (CAP) and acute pelvic infection caused by susceptible strains of certain designated organisms in both the US and the EU. Additional approved indications in the US include complicated skin and skin structure infection (cSSSI) and complicated urinary tract infection (cUTI). Ertapenem is approved for use in adults in both the US and the EU and in paediatric patients aged >or=3 months in the US.Ertapenem has a broad spectrum of in vitro activity against Gram-negative pathogens, including extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae, Gram-positive pathogens and anaerobic pathogens. It has similar efficacy to comparator antibacterials such as piperacillin/tazobactam in cSSSI (including diabetic foot infection), cIAI and acute pelvic infection and ceftriaxone with or without metronidazole in cIAI, cUTI and CAP. The drug has also shown efficacy in the treatment of paediatric patients with complicated community-acquired bacterial infections. Ertapenem has a convenient once-daily administration schedule and is generally well tolerated. Thus, ertapenem is an important option for the empirical treatment of complicated community-acquired bacterial infections in hospitalised patients.     

Doripenem: a review of its use in the treatment of bacterial infections

Doripenem, a parenteral, broad-spectrum antibacterial agent of the carbapenem family, is indicated as empirical therapy in serious bacterial infections in adults. Doripenem is indicated in Japan for use as a single agent in intra-abdominal infections (IAIs), lower respiratory tract infections (including nosocomial pneumonia), complicated urinary tract infections (cUTIs) and a variety of other bacterial infections, such as complicated skin and skin structure infections (cSSSIs), obstetric and gynaecological infections, serious ear, nose and throat infections, sepsis and endocarditis, dental and oral surgical infection, and ophthalmic infection caused by various susceptible strains of Gram-negative, Gram-positive or anaerobic bacteria. Doripenem is indicated in the US for the treatment of complicated IAIs (cIAIs) or cUTIs, including pyelonephritis, caused by susceptible strains of designated pathogens, and in the EU for the treatment of nosocomial pneumonia (including ventilator-associated pneumonia [VAP]), cIAIs or cUTIs.Doripenem has a broad spectrum of in vitro activity against Gram-positive and Gram-negative bacteria, including extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae, and anaerobic pathogens. The drug also has a low propensity to select for resistance and is suitable for the prolonged infusions that may be required to achieve pharmacodynamic/pharmacokinetic targets for bactericidal activity (and therefore efficacy) against pathogens with increased MICs (minimum concentrations required to inhibit the pathogens). Doripenem is no less effective than other antibacterial agents, including meropenem, imipenem/cilastin, piperacillin/tazobactam or levofloxacin in a wide range of serious bacterial infections, such as complicated lower respiratory infections, nosocomial pneumonia (including VAP), cIAIs and cUTIs, and is well tolerated. Thus, doripenem is a valuable addition to the options available for the empirical treatment of serious bacterial infections in hospitalized patients.     

Cefditoren pivoxil: a review of its use in the treatment of bacterial infections

Cefditoren pivoxil (Spectracef, Meiact) is a third-generation oral cephalosporin with a broad spectrum of activity against pathogens, including both Gram-positive and -negative bacteria, and is stable to hydrolysis by many common beta-lactamases. Cefditoren pivoxil is approved for use in the treatment of acute exacerbations of chronic bronchitis (AECB), mild-to-moderate community-acquired pneumonia (CAP), acute maxillary sinusitis, acute pharyngitis/tonsillitis and uncomplicated skin and skin structure infections (indications may differ between countries).In clinical trials in adults and adolescents, cefditoren pivoxil demonstrated good clinical and bacteriological efficacy in AECB, CAP, acute maxillary sinusitis, acute pharyngitis/tonsillitis and uncomplicated skin and skin structure infections and was generally well tolerated. Thus, cefditoren pivoxil is a good option for the treatment of adult and adolescent patients with specific respiratory tract or skin infections, particularly if there is concern about Streptococcus pneumoniae with decreased susceptibility to penicillin, or beta-lactamase-mediated resistance among the common community-acquired pathogens.     

Meropenem: a review of its use in the treatment of serious bacterial infections

Meropenem (Merrem, Meronem) is a broad-spectrum antibacterial agent of the carbapenem family, indicated as empirical therapy prior to the identification of causative organisms, or for disease caused by single or multiple susceptible bacteria in both adults and children with a broad range of serious infections. Meropenem is approved for use in complicated intra-abdominal infection (cIAI), complicated skin and skin structure infection (cSSSI) and bacterial meningitis (in paediatric patients aged > or = 3 months) in the US, and in most other countries for nosocomial pneumonia, cIAI, septicaemia, febrile neutropenia, cSSSI, bacterial meningitis, complicated urinary tract infection (UTI), obstetric and gynaecological infections, in cystic fibrosis patients with pulmonary exacerbations, and for the treatment of severe community-acquired pneumonia (CAP). Meropenem has a broad spectrum of in vitro activity against Gram-positive and Gram-negative pathogens, including extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae. It has similar efficacy to comparator antibacterial agents, including: imipenem/cilastatin in cIAI, cSSSI, febrile neutropenia, complicated UTI, obstetric or gynaecological infections and severe CAP; clindamycin plus tobramycin or gentamicin in cIAI or obstetric/gynaecological infections; cefotaxime plus metronidazole in cIAI; cefepime and ceftazidime plus amikacin in septicaemia or febrile neutropenia; and ceftazidime, clarithromycin plus ceftriaxone or amikacin in severe CAP. Meropenem has also shown similar efficacy to cefotaxime in paediatric and adult patients with bacterial meningitis, and to ceftazidime when both agents were administered with or without tobramycin in patients with cystic fibrosis experiencing acute pulmonary exacerbations. Meropenem showed greater efficacy than ceftazidime or piperacillin/tazobactam in febrile neutropenia, and greater efficacy than ceftazidime plus amikacin or tobramycin in patients with nosocomial pneumonia. Meropenem is well tolerated and has the advantage of being suitable for administration as an intravenous bolus or infusion. Its low propensity for inducing seizures means that it is suitable for treating bacterial meningitis and is the only carbapenem approved in this indication. Thus, meropenem continues to be an important option for the empirical treatment of serious bacterial infections in hospitalized patients.     

Levofloxacin : a review of its use as a high-dose, short-course treatment for bacterial infection

Levofloxacin (Levaquin) is a fluoroquinolone antibacterial that is the L-isomer of ofloxacin. A high-dose (750 mg) short-course (5 days) of once-daily levofloxacin is approved for use in the US in the treatment of community-acquired pneumonia (CAP), acute bacterial sinusitis (ABS), complicated urinary tract infections (UTI) and acute pyelonephritis (AP).The broad spectrum antibacterial profile of levofloxacin means that monotherapy is often a possibility in patients with CAP at times when other agents may require combination therapy, although levofloxacin can be used in combination therapy when necessary. The high-dose, short-course levofloxacin regimen maximizes its concentration-dependent bactericidal activity and may reduce the potential for resistance to emerge. In addition, this regimen lends itself to better compliance because of the shorter duration of treatment and the convenient once-daily administration schedule. Oral levofloxacin is rapidly absorbed and is bioequivalent to the intravenous formulation; importantly, patients can transition between the formulations, which results in more options in regards to the treatment regimen and the potential for patients with varying degrees of illness to be treated. Levofloxacin has good tissue penetration and an adequate concentration can be maintained in the urinary tract to treat uropathogens. Levofloxacin is generally well tolerated and has good efficacy in the treatment of patients with CAP, ABS, complicated UTI and AP. The efficacy and tolerability of levofloxacin 500 mg once daily for 10 days in patients with CAP, ABS and UTIs is well established, and the high-dose, short-course levofloxacin regimen has been shown to be noninferior to the 10-day regimen in CAP and ABS, and to have a similar tolerability profile. Similarly, the high-dose, short-course levofloxacin regimen is noninferior to ciprofloxacin in patients with complicated UTI or AP. Thus, levofloxacin is a valuable antimicrobial agent that has activity against a wide range of bacterial pathogens; however, its use should be considered carefully so that the potential for resistance selection can be minimized and its usefulness in severe infections and against a range of penicillin- and macrolide-resistant pathogens can be maintained.     

Gatifloxacin: a review of its use in the treatment of bacterial infections in the US

Gatifloxacin (Tequin) is an 8-methoxy fluoroquinolone approved in the US for use in the treatment of community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), acute sinusitis, uncomplicated and complicated urinary tract infections (UTIs), pyelonephritis, gonorrhoea and uncomplicated skin and skin structure infections. Gatifloxacin has a broad spectrum of antibacterial activity in vitro and good clinical and bacteriological efficacy in patients with indicated infections following once-daily administration by the intravenous or oral routes. It is generally well tolerated; the most common adverse events are associated with the gastrointestinal tract and CNS. Recent approvals for the use of gatifloxacin in the treatment of CAP due to multidrug-resistant Streptococcus pneumoniae (MDRSP) and in uncomplicated skin and skin structure infections extend the role of this drug in the treatment of bacterial infections in the US.     

Ertapenem: a review of its use in the management of bacterial infections

Ertapenem, a carbapenem antibacterial, has in vitro activity against many Gram- negative (including Enterobacteriaceae) and Gram-positive aerobic and anaerobic bacteria that are commonly associated with various infections.Once-daily parenteral (intravenous or intramuscular) ertapenem 1g was as effective as comparator antimicrobial agents (piperacillin/tazobactam or ceftriaxone +/- metronidazole) in patients with bacterial infections in randomised, double-blind, multicentre clinical trials. Response rates with ertapenem were 84% and 87% (combined microbiological and clinical) in patients with complicated intra-abdominal infections (CIAI), 82% (clinical) in patients with complicated skin and skin structure infections (CSSSI), 86% and 92% (microbiological) in patients with complicated urinary tract infections (CUTI), 92% (clinical) in patients with community-acquired pneumonia (CAP) associated with typical pathogens and 94% (clinical) in patients with acute pelvic infection. Respective response rates were statistically equivalent to those with comparators (81-94%). The efficacy of ertapenem was equivalent to that of piperacillin/tazobactam in patients infected with Enterobacteriaceae or anaerobes and to ceftriaxone in patients infected with Enterobacteriaceae. Ertapenem was generally well tolerated by patients with bacterial infections, with most adverse events being mild to moderate in severity. The most common ertapenem-associated adverse events were diarrhoea, infused vein complication, nausea, headache, vaginitis in females, phlebitis and/or thrombophlebitis and vomiting. CONCLUSION: Ertapenem is a broad-spectrum parenteral antibiotic with activity against many Gram-negative (including Enterobacteriaceae) and Gram-positive aerobic and anaerobic bacteria and is suitable for once-daily administration. Ertapenem has a role in the treatment of CAP associated with typical respiratory pathogens and is of particular value in the treatment of polymicrobial infections (such as CIAI, CSSSI, CUTI and acute pelvic infections), especially where Enterobacteriaceae and anaerobic bacteria are involved.     

Moxifloxacin: a review of its use in the management of bacterial infections

Moxifloxacin (Avelox) is a fluoroquinolone antibacterial with a methoxy group in the C-8 position and a bulky C-7 side chain. Moxifloxacin is approved for use in the treatment of acute exacerbations of chronic bronchitis (AECB), community-acquired pneumonia (CAP), acute bacterial sinusitis and uncomplicated skin and skin structure infections (approved indications may differ between countries). Moxifloxacin has a broad spectrum of antibacterial activity, including activity against penicillin-resistant Streptococcus pneumoniae. It achieves good tissue penetration and has a convenient once-daily administration schedule, as well as being available in both intravenous and oral formulations in some markets. Moxifloxacin has good efficacy in the treatment of patients with AECB, CAP, acute bacterial sinusitis and uncomplicated skin and skin structure infections, and is generally well tolerated. Thus, moxifloxacin is an important option in the treatment of bacterial infections.     

Cefdinir: a review of its use in the management of mild-to-moderate bacterial infections

Cefdinir (Omnicef) is an oral third-generation cephalosporin with good in vitro activity against many pathogens commonly causative in community-acquired infections. The drug provides good coverage against Haemophilus influenzae, Moraxella catarrhalis and penicillin-susceptible Streptococcus pneumoniae, the most common respiratory tract pathogens. Cefdinir is stable to hydrolysis by commonly occurring plasmid-mediated beta-lactamases and retains good activity against beta-lactamase-producing strains of H. influenzae and M. catarrhalis. The drug distributes into various tissues (e.g. sinus and tonsil) and fluids (e.g. middle ear), and has a pharmacokinetic profile that allows for once- or twice-daily administration.Cefdinir, administered for 5 or 10 days, has shown good clinical and bacteriological efficacy in the treatment of a wide range of mild-to-moderate infections of the respiratory tract and skin in adults, adolescents and paediatric patients in randomised, controlled trials. In adults and adolescents, cefdinir is an effective treatment for both lower (acute bacterial exacerbations of chronic bronchitis [ABECB], community-acquired pneumonia) and upper (acute bacterial rhinosinusitis, streptococcal pharyngitis) respiratory tract infections, and uncomplicated skin infections. Its bacteriological and clinical efficacy in patients with lower respiratory tract infections was equivalent to that of comparator agents (cefprozil [bacteriological only], loracarbef, cefuroxime axetil and cefaclor). In one trial in patients with ABECB, cefdinir produced a higher rate of clinical cure than cefprozil (95% CIs indicated nonequivalence). Cefdinir also produced good clinical and bacteriological responses equivalent to responses with amoxicillin/clavulanic acid in patients with acute bacterial rhinosinusitis. In addition, it was at least as effective as penicillin V (phenoxymethylpenicillin) in streptococcal pharyngitis/tonsillitis and as effective as cefalexin in uncomplicated skin infections. In paediatric patients aged > or =6 months, cefdinir showed similar efficacy to that of amoxicillin/clavulanic acid or cefprozil in acute otitis media, and cefalexin in uncomplicated skin infections. Cefdinir given for 5 or 10 days was at least as effective as penicillin V for 10 days in patients with streptococcal pharyngitis/tonsillitis. Cefdinir is usually well tolerated. Diarrhoea was the most common adverse event in trials in all age groups. Although the incidence of diarrhoea in cefdinir recipients was generally higher than in adults and adolescents treated with comparators, discontinuation rates due to adverse events were generally similar for cefdinir and comparator groups.In conclusion, cefdinir is a third-generation cephalosporin with a broad spectrum of antibacterial activity encompassing pathogens that are commonly causative in infections of the respiratory tract or skin and skin structure. Depending on the infection being treated, cefdinir can be administered as a convenient once- or twice-daily 5- or 10-day regimen. Clinical evidence indicates that cefdinir is an effective and generally well tolerated drug with superior taste over comparator antibacterial agents and is therefore a good option for the treatment of adults, adolescents and paediatric patients with specific mild-to-moderate respiratory tract or skin infections, particularly in areas where beta-lactamase-mediated resistance among common community-acquired pathogens is a concern.     

Gatifloxacin: a review of its use in the management of bacterial infections.

Gatifloxacin is an 8-methoxy fluoroquinolone antibacterial agent. The drug has a broader spectrum of antibacterial activity than the older fluoroquinolones (e.g. ciprofloxacin) and shows good activity against many Gram-positive and Gram-negative pathogens, atypical organisms and some anaerobes. Notably, gatifloxacin is highly active against both penicillin-susceptible and -resistant strains of Streptococcus pneumoniae, a common causative pathogen in community-acquired pneumonia (CAP), acute sinusitis and acute bacterial exacerbations of bronchitis. Gatifloxacin is absorbed well from the gastrointestinal tract (oral bioavailability is almost 100%). Therefore, patients can be switched from intravenous to oral therapy without an adjustment in dosage. High concentrations of gatifloxacin are achieved in plasma and target tissues/fluids. Gatifloxacin has a long plasma elimination half-life, thus allowing once-daily administration. Few clinically significant interactions between gatifloxacin and other drugs have been reported. In patients with CAP, clinical response rates in recipients of intravenous/oral gatifloxacin 400 mg/day ranged from 86.8 to 98.0% and rates of bacterial eradication ranged from 83.1 to 100% (up to 28 days post-treatment). Gatifloxacin showed efficacy similar to that of amoxicillin/clavulanic acid, ceftriaxone (with or without erythromycin) with or without stepdown to clarithromycin, levofloxacin or clarithromycin. Gatifloxacin was as effective as clarithromycin or amoxicillin/clavulanic acid, and was significantly more effective (in terms of clinical response; p < 0.035) than 7 to 10 days' treatment with cefuroxime axetil in the treatment of acute exacerbations of chronic bronchitis. In acute sinusitis, gatifloxacin showed clinical efficacy similar to that of clarithromycin, trovafloxacin or amoxicillin/clavulanic acid. Genitourinary infections were also successfully treated with gatifloxacin. Gatifloxacin is generally well tolerated. Its tolerability profile was broadly similar to those of comparator agents in comparative trials. The most common adverse events are gastrointestinal symptoms (oral formulation) and injection site reactions. CONCLUSIONS: Gatifloxacin has an extended spectrum of antibacterial activity and provides better coverage of Gram-positive organisms (e.g. S. pneumoniae) than some older fluoroquinolones. The drug has favourable pharmacokinetic properties, is administered once daily and is at least as well tolerated as other fluoroquinolones. Gatifloxacin is a useful addition to the fluoroquinolones currently available for use in the clinical setting and has an important role in the management of adult patients with various bacterial infections. As with other fluoroquinolones, careful control of gatifloxacin usage in the community is important in order to prevent the emergence of bacterial resistance and thus preserve the clinical value of this agent.     

左氧氟沙星治疗细菌性感染70例

目的：观察左氧氟沙星治疗细菌感染的疗效和安全性。方法：以左氧氟沙星治疗细菌性感染７０例（男性３５例，女性３５例，年龄５４±ｓ１５ａ），其中下呼吸道感染４０例，尿路感染３０例，剂量一般为０．２ｇ，ｐｏ，ｂｉｄ，疗程７～１４ｄ；单纯性下尿路感染为０．２ｇ，ｐｏ，ｑｄ，疗程５～７ｄ。结果：总有效率９３％，细菌清除率８８％，不良反应轻微，呈一过性，发生率为６％。结论：左氧氟沙星治疗细菌性感染有效而安全。     

Nitazoxanide: a review of its use in the treatment of gastrointestinal infections

Nitazoxanide (Alinia, Daxon, Dexidex, Paramix, Kidonax, Colufase, Annita) has in vitro activity against a variety of microorganisms, including a broad range of protozoa and helminths. Nitazoxanide is effective in the treatment of protozoal and helminthic infections, including Cryptosporidium parvum or Giardia lamblia, in immunocompetent adults and children, and is generally well tolerated. Nitazoxanide is a first-line choice for the treatment of illness caused by C. parvum or G. lamblia infection in immunocompetent adults and children, and is an option to be considered in the treatment of illnesses caused by other protozoa and/or helminths.     

Piperacillin/tazobactam: an updated review of its use in the treatment of bacterial infections.

Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity encompassing most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria, including many pathogens producing beta-lactamases. Evidence from clinical trials in adults has shown that piperacillin/tazobactam, administered in an 8:1 ratio, is an effective treatment for patients with lower respiratory tract, intra-abdominal, urinary tract, gynaecological and skin/soft tissue infections, and for fever in patients with neutropenia. Combination regimens of piperacillin/tazobactam plus an aminoglycoside are used to treat patients with severe nosocomial (hospital-acquired) infections. In clinical trials, piperacillin/tazobactam was significantly more effective than ticarcillin/clavulanic acid in terms of clinical and microbiological outcome in patients with community-acquired pneumonia. In patients with intra-abdominal infections, clinical and bacteriological response rates were significantly higher with piperacillin/tazobactam than with imipenem/cilastatin (administered at a dosage lower than is recommended in countries outside Scandinavia). Piperacillin/tazobactam in combination with amikacin was at least as effective as ceftazidime plus amikacin in the treatment of ventilator-associated pneumonia and was significantly more effective than ceftazidime plus amikacin in the empirical treatment of febrile episodes in patients with neutropenia or granulocytopenia. In other trials, the efficacy of piperacillin/tazobactam was similar to that of standard aminoglycoside-containing and other treatment regimens in patients with intra-abdominal, skin/soft tissue or gynaecological infections. Piperacillin/tazobactam is generally well tolerated. The most frequent adverse events are gastrointestinal symptoms (most commonly diarrhoea) and skin reactions. The incidence of adverse events with piperacillin/tazobactam is higher when the combination is given in combination with an aminoglycoside than when given as monotherapy. CONCLUSION: Because of the broad spectrum of antibacterial activity provided by piperacillin/tazobactam, it is useful for the treatment of patients with polymicrobial infections caused by aerobic or anaerobic beta-lactamase-producing bacteria. Piperacillin/tazobactam appears to have a particularly useful role in the treatment of patients with intra-abdominal infections and, in combination with amikacin, in the treatment of patients with febrile neutropenia, especially given the current prevalence of Gram-positive infections in this group.     

Caspofungin: a review of its use in the treatment of fungal infections

Caspofungin (Cancidas) is the first of a new class of antifungal agents, the echinocandins, that inhibit the synthesis of the fungal cell wall component beta-(1,3)-D-glucan. Caspofungin is administered once daily by slow intravenous infusion and is used to treat infections caused by Candida spp. and Aspergillus spp.Caspofungin is a valuable new antifungal agent with a novel mechanism of action. In comparative clinical trials, caspofungin was no less effective than liposomal amphotericin B in the empirical treatment of neutropenic patients with persistent fever, amphotericin B deoxycholate in the treatment of invasive candidiasis or fluconazole in the treatment of oesophageal candidiasis. Caspofungin also displayed broadly similar efficacy to amphotericin B deoxycholate in oesophageal or oropharyngeal candidiasis and was effective as salvage therapy in patients with invasive aspergillosis who were refractory to or intolerant of standard therapy. The tolerability profile of caspofungin was similar to that of fluconazole and superior to that of amphotericin B deoxycholate and liposomal amphotericin B. Therefore, in the appropriate indications, caspofungin is a viable alternative to amphotericin B deoxycholate, liposomal amphotericin B or fluconazole.     

Cefpodoxime proxetil: a review of its use in the management of bacterial infections in paediatric patients

Cefpodoxime proxetil is an oral third generation cephalosporin with a broad spectrum of antibacterial activity. The drug has in vitro activity against many common Gram-positive and Gram-negative pathogens associated with common paediatric infections, making the drug a useful option for empirical therapy. In randomised controlled trials conducted in children with acute otitis media, oral cefpodoxime proxetil 8 to 10 mg/kg/day (usually administered in 2 divided doses) for 5 to 10 days was at least as effective as standard regimens of amoxicillin/ clavulanic acid, cefixime, cefuroxime axetil or cefaclor as assessed by either clinical or bacteriological criteria. Cefpodoxime 8 to 10 mg/kg/day (administered in 2 divided doses) for 5 to 10 days was at least as effective as standard 10-day regimens of penicillin V in the treatment of children with pharyngitis and/or tonsillitis. Significant differences in favour of cefpodoxime proxetil were demonstrated in terms of clinical (1 study) and bacteriological (2 studies) criteria. The clinical efficacy of 5 days of treatment with cefpodoxime proxetil is similar to that of 10 days of treatment with penicillin V. In children with lower respiratory tract infections (primarily pneumonia), clinical and bacteriological efficacy rates achieved with cefpodoxime proxetil treatment were similar to those produced by cefuroxime axetil or amoxicillin/clavulanic acid in randomised controlled trials. Cefpodoxime proxetil also demonstrated clinical efficacy in paediatric patients with skin and soft tissue infections. In randomised studies that included both adults and children with a variety of infections (e.g. abscess, atheroma, furuncle and carbuncle, infected wounds, cellulitis), cefpodoxime proxetil showed efficacy similar to that of cefuroxime axetil or cefaclor. Cefpodoxime proxetil is well tolerated by paediatric patients, with adverse events (primarily gastrointestinal tract disturbances and skin rashes) that are consistent with those reported for other oral cephalosporins. CONCLUSION: Cefpodoxime proxetil is a third generation cephalosporin with a broad spectrum of antibacterial activity and a favourable pharmacokinetic profile which allows twice-daily administration. It is generally well tolerated and demonstrates good bacteriological and clinical efficacy in paediatric patients with various infectious diseases, including acute otitis media, tonsillitis and/or pharyngitis. Based on these characteristics, cefpodoxime proxetil is a suitable option for the treatment of paediatric patients with various common bacterial infections.     

Cefuroxime axetil: an updated review of its use in the management of bacterial infections

Cefuroxime axetil, a prodrug of the cephalosporin cefuroxime, has proven in vitro antibacterial activity against several gram-positive and gram-negative organisms, including those most frequently associated with various common community-acquired infections. In numerous randomised, controlled trials, 5 to 10 days' treatment with oral cefuroxime axetil (250 or 500 mg twice daily) was an effective treatment in patients with upper (URTI) and lower respiratory tract infections (LRTI) as assessed by clinical and bacteriological criteria. The drug was as effective as several other cephalosporins, quinolones, macrolides and amoxicillin/clavulanic acid. Shorter courses (5 to 10 days') of cefuroxime axetil were at least as effective as a 10 day course. Furthermore, sequential therapy with intravenous cefuroxime (750 mg 2 or 3 times daily for 2 to 5 days) followed by oral cefuroxime axetil (500 mg twice daily for 3 to 8 days) proved an effective treatment in adult patients with community-acquired pneumonia (CAP). This approach provided similar efficacy to intravenous ampicillin/sulbactam followed by oral amoxicillin/clavulanic acid, a full parenteral course of cefuroxime, or intravenous then oral azithromycin or clarithromycin. Additionally, cefuroxime axetil was an effective treatment in patients with genitourinary, skin and soft-tissue infections, and erythema migrans associated with early stage Lyme disease. The drug is well tolerated by adult and paediatric patients, with adverse effects that are consistent with those of other cephalosporins. The majority of adverse events (primarily gastrointestinal disturbances) were mild to moderate in intensity and reversible upon discontinuation of treatment, with very few serious adverse events reported. Conclusions: Cefuroxime axetil is a broad spectrum antibacterial agent with a pharmacokinetic profile that permits convenient twice-daily administration. The drug is an effective and well tolerated treatment in patients with various infections, including otitis media, pharyngitis, sinusitis, CAP and acute exacerbations of chronic bronchitis. Cefuroxime axetil proved effective as a component of intravenous/oral sequential therapy in the treatment of CAP, although there are currently no dosage recommendations available for this regimen in some countries. Cefuroxime axetil may be considered as an empirical therapy for a range of community-acquired infections, including those in which beta-lactamase-producing strains of common respiratory pathogens are identified as the causative organisms. In an era of rapidly emerging bacterial resistance, empirical treatment with bacterial agents, potentially preventing the emergence of bacterial resistance to agents such as cefuroxime axetil may ensure the appropriate use of newer antibacterial agents, potentially preventing the emergence of bacterial resistance to these newer drugs.     

Piperacillin/tazobactam: a pharmacoeconomic review of its use in moderate to severe bacterial infections.

Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria. Piperacillin/tazobactam is effective and well-tolerated in patients with lower respiratory tract infections (LRTI), intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia. In comparative clinical trials against various other antibacterial regimens, piperacillin/tazobactam has shown higher clinical success rates, particularly in the treatment of patients with intra-abdominal infections and febrile neutropenia. Cost analyses of piperacillin/tazobactam have been variable, in part, because of differences in specific costs included. Three US cost analyses found that piperacillin/tazobactam had lower total medical costs than clindamycin plus gentamicin or imipenem/cilastatin in intra-abdominal infections, and ticarcillin/ clavulanic acid in community-acquired pneumonia. Piperacillin/tazobactam plus amikacin had lower total costs than ceftazidime plus amikacin in another cost analysis of patients with febrile neutropenic episodes modelled in nine European countries. However, piperacillin/tazobactam plus tobramycin was more costly than ceftazidime plus tobramycin in hospital-acquired pneumonia in a US cost analysis. In cost-effectiveness analyses, all studies of intra-abdominal infections, pneumonia and febrile neutropenic episodes consistently reported lower costs per unit of effectiveness versus comparators. Piperacillin/tazobactam was dominant (greater efficacy and lower costs) versus imipenem/cilastatin in intra-abdominal infections and ceftriaxone, ciprofloxacin or meropenem in pneumonia. Piperacillin/tazobactam plus amikacin was dominant over ceftazidime plus amikacin in the treatment of febrile neutropenic episodes. In a cost-effectiveness analysis of skin and soft tissue infection, piperacillin/tazobactam had lower costs per successfully treated patient than ceftriaxone or cefotaxime, but a slightly higher cost-effectiveness ratio than amoxicillin/clavulanic acid. All cost-effectiveness analyses were based on decision-analytical models. CONCLUSIONS: Piperacillin/tazobactam is likely to reduce overall treatment costs of moderate to severe bacterial infections by increasing initial treatment success, thereby reducing the length of hospital stay and the use of additional antibacterials. Piperacillin/tazobactam has shown clinical and economic advantages over standard antibacterial regimens in the treatment of intra-abdominal infections, LRTIs, febrile episodes in patients with neutropenia, and skin and soft tissue infections, although more complete published data are needed to confirm these results. Present data regarding clinical efficacy, bacterial resistance and costs would support the use of piperacillin/tazobactam as an empirical first-line option in moderate to severe bacterial infections.     

Linezolid: a pharmacoeconomic review of its use in serious Gram-positive infections

Linezolid (Zyvox), the first available oxazolidinone antibacterial agent, has good activity against Gram-positive pathogens, including multidrug-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Randomised multicentre trials in patients with various types of serious Gram-positive infections showed that clinical cure rates with linezolid were similar to those with vancomycin or teicoplanin. In some subgroup analyses, which must be interpreted with a degree of caution, clinical advantages were noted for linezolid (e.g. versus vancomycin in confirmed MRSA nosocomial pneumonia and MRSA-complicated skin and soft tissue infections). Although generally well tolerated, gastrointestinal adverse effects are relatively common with linezolid and it has been associated with thrombocytopenia and myelosuppression. The oral bioavailability of linezolid is approximately 100%, thus allowing sequential intravenous-to-oral administration without changing the drug or dosage regimen. Healthcare resource use data from various countries indicate that this practical advantage translates into at least a trend towards reduced length of hospital stay compared with vancomycin, which may offset its several-fold higher acquisition cost. Modelled analyses from the US, despite some limitations, indicate that, compared with vancomycin, linezolid is associated with lower total hospitalisation costs for the treatment of patients with cellulitis and has a favourable incremental cost-effectiveness ratio of approximately US30,000 dollars per QALY gained (2001 value) for patients with ventilator-associated pneumonia. Broadly similar results have also been reported in modelled analyses from other countries. In conclusion, for patients with serious Gram-positive infections, including those caused by suspected or proven multidrug-resistant pathogens such as MRSA, linezolid is an effective and generally well tolerated therapeutic option. Linezolid is currently the only antibacterial agent with good activity against MRSA that can be administered orally (as well as intravenously). It may be particularly useful as an alternative to vancomycin in patients who have impaired renal function, poor or no intravenous access, require outpatient therapy, or who have been unable to tolerate glycopeptides. Healthcare resource use studies and pharmacoeconomic analyses generally support the use of linezolid in some subgroups of patients, although results should be interpreted with due consideration of the study limitations.     

Linezolid: a review of its use in the management of serious gram-positive infections

Linezolid is the first of a new class of antibacterial drugs, the oxazolidinones. It has inhibitory activity against a broad range of gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-intermediate S. aureus (GISA), vancomycin-resistant enterococci (VRE) and penicillin-resistant Streptococcus pneumoniae. The drug also shows activity against certain anaerobes, including Clostridium perfringens, C. difficile, Peptostreptococcus spp. and Bacteroidesfragilis. In controlled phase III studies, linezolid was as effective as vancomycin in the treatment of patients with infections caused by methicillin-resistant staphylococci and also demonstrated efficacy against infections caused by VRE. Further phase III studies have demonstrated that linezolid is an effective treatment for patients with nosocomial pneumonia, for hospitalised patients with community-acquired pneumonia, and for patients with complicated skin or soft tissue infections (SSTIs). In these studies, linezolid was as effective as established treatments, including third-generation cephalosporins in patients with pneumonia, and oxacillin in patients with complicated SSTIs. Oral linezolid 400 or 600mg twice daily was as effective as clarithromycin 250mg twice daily or cefpodoxime proxetil 200mg twice daily in the treatment of patients with uncomplicated SSTIs or community-acquired pneumonia. Linezolid is a generally well tolerated drug. The most frequently reported adverse events in linezolid recipients were diarrhoea, headache, nausea and vomiting. Thrombocytopenia was also documented in a small proportion (about 2%) of patients treated with the drug. CONCLUSIONS: Linezolid has good activity against gram-positive bacteria, particularly multidrug resistant strains of S. aureus (including GISA), Enterococcus faecium and E. faecalis (including VRE). In controlled clinical trials, linezolid was as effective as vancomycin in eradicating infections caused by methicillin-resistant Staphylococcus spp. and has demonstrated efficacy against infections caused by VRE. As the level of resistance to vancomycin increases among S. aureus and enterococci, linezolid is poised to play an important role in the management of serious gram-positive infections.