Norfloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use

Norfloxacin is one of the new 4-quinolone antibacterial agents. A fluorinated piperazinyl-substituted congener of nalidixic acid, it demonstrates a much wider in vitro antibacterial spectrum and greater potency than the parent compound. Its antibacterial activity against most Gram-negative pathogens is enhanced in comparison to nalidixic acid, but is similar to that of some of the other new 4-quinolones like enoxacin, and slightly less than that of ciprofloxacin. Unlike nalidixic acid, norfloxacin is also active against Pseudomonas aeruginosa and some Gram-positive organisms. In acute or uncomplicated urinary tract infections, norfloxacin has repeatedly been shown to be as effective as co-trimoxazole. Single studies have demonstrated a significantly better bacteriological cure rate with norfloxacin than with pipemidic acid, and similar cure rates with norfloxacin and both a nalidixic acid/sodium citrate mixture and amoxycillin. Similar results were found in a few studies comparing norfloxacin to pipemidic acid or amoxycillin in patients with chronic and/or complicated urinary tract infections. Norfloxacin is as effective as spectinomycin in gonorrhoea due to penicillin-resistant N. gonorrhoeae, and cures bacterial gastroenteritis caused by several gastrointestinal pathogens. Norfloxacin appears to be well tolerated and may have a low propensity to select for bacterial resistance during clinical use, although the latter needs further confirmation.     

Cinoxacin (Cinobac, Eli Lilly & Co.)

Cinoxacin, a synthetic organic acid antibacterial agent, related structurally to nalidixic and oxolinic acid, has been approved for the treatment of initial and recurrent urinary tract infections (UTIs) caused by susceptible gram-negative microorganisms. The role of cinoxacin in the treatment of UTIs, compared with the usual first-line agents, is uncertain at this time. The efficacy of cinoxacin in the treatment of pyelonephritis, compared with these proven agents, has been examined in only small numbers of patients, and cinoxacin is more expensive than these agents. Cinoxacin may prove valuable in the treatment of prostatitis and in the prophylaxis of recurrent UTIs; further study in these areas is warranted. In the routine treatment of acute UTIs, cinoxacin perhaps should be reserved only for those patients with organisms resistant to usual first-line agents or those who fail to respond to therapy with these agents. In this respect, cinoxacin may, in the future, replace nalidixic acid.     

Cinoxacin: Mechanism of Action,Spectrum of Activity,Pharmacokinetics, Adverse Reactions,and Therapeutic Indications

Cinoxacin, a chemotherapeutic agent that inhibits bacterial DNA synthesis, has recently been approved for the treatment of initial and recurrent bacterial urinary tract infections. Although closely related to nalidixic acid, cinoxacin possesses some distinct characteristics: rapid attainment of therapeutic urinary concentrations and greater activity against strains of Enterobacteriaceae that cause urinary tract infections. Biopharmaceutical properties include serum protein binding of approximately 70%, 50–60% excretion of intact drug in the urine of patients with normal renal function, and an elimination half-life of approximately one hour. The elimination half-life is increased in patients with decreased renal function and when probenecid is coadministered. Adverse events occur infrequently and consist of nausea, vomiting, headache, dizziness, and hypersensitivity reactions. The drug compares favorably with standard therapies for the treatment of bacterial cystitis and recurrent urinary tract infections. Initial studies demonstrate that cinoxacin has substantial efficacy as a prophylactic agent for those women who experience recurrent, symptomatic urinary tract infections.     

Ciprofloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use

Ciprofloxacin is one of a new generation of fluorinated quinolones structurally related to nalidixic acid. The primary mechanism of action of ciprofloxacin is inhibition of bacterial DNA gyrase. It is a broad spectrum antibacterial drug to which most Gram-negative bacteria are highly susceptible in vitro and many Gram-positive bacteria are susceptible or moderately susceptible. Unlike most broad spectrum antibacterial drugs, ciprofloxacin is effective after oral or intravenous administration. Ciprofloxacin has been most extensively studied following oral administration. It attains concentrations in most tissues and body fluids which are at least equivalent to the minimum inhibitory concentration designated as the breakpoint for bacterial susceptibility in vitro. The results of clinical trials with orally and intravenously administered ciprofloxacin have confirmed the potential for its use in a wide range of infections, which was suggested by its in vitro antibacterial and pharmacokinetic profiles. It has proven an effective treatment for many types of systemic infections as well as for both acute and chronic infections of the urinary tract. Ciprofloxacin generally appeared to be at least as effective as alternative orally administered antibacterial drugs in the indications in which they were compared, and in some indications, to parenterally administered antibacterial therapy. However, further studies are needed to fully clarify the comparative efficacy of ciprofloxacin and standard antibacterial therapies. Bacterial resistance to ciprofloxacin develops infrequently, both in vitro and clinically, except in the setting of pseudomonal respiratory tract infections in cystic fibrosis patients. The drug is also well tolerated. Thus, as an orally active, broad spectrum and potent antibacterial drug, ciprofloxacin offers a valuable alternative to broad spectrum parenterally administered antibacterial drugs for use in a wide range of clinical infections, including difficult infections due to multiresistant pathogens.     

Ofloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use

Ofloxacin is one of a new generation of fluorinated quinolones structurally related to nalidixic acid. It is an orally administered broad spectrum antibacterial drug active against most Gram-negative bacteria, many Gram-positive bacteria and some anaerobes. Ciprofloxacin is the only other quinolone with superior in vitro antibacterial activity. However, the pharmacokinetic profile of ofloxacin is superior to that of ciprofloxacin, with more rapid absorption and a peak serum concentration several times higher. Moreover, ofloxacin achieves high concentrations in most tissues and body fluids. The results of clinical trials with ofloxacin have confirmed the potential for use in a wide range of infections, which was indicated by its in vitro antibacterial and pharmacokinetic profiles. It has proven effective against a high percentage of infections caused by Gram-negative organisms, slightly less effective against Gram-positive infections, and effective against some anaerobic infections. Clinical efficacy has also been confirmed in a variety of systemic infections as well as in acute and chronic urinary tract infections, and ofloxacin has generally appeared to be at least as effective as alternative orally administered antibacterial drugs. Ofloxacin is well tolerated and, although experience with the drug in clinical practice to date is limited, bacterial resistance does not appear to develop readily. Thus, ofloxacin is an orally active drug which offers a valuable alternative to other broad spectrum antibacterial drugs.     

Pefloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use

Pefloxacin is a fluorinated quinolone that is structurally related to nalidixic acid. It can be administered both orally and intravenously, and has a broad spectrum of in vitro activity against Gram-negative organisms and staphylococci. The pharmacokinetic profile of pefloxacin is characterised by high bioavailability after oral administration, a long half-life and good penetration of tissue and body fluids. Data from mainly non-comparative studies suggest that pefloxacin has the potential for use in a variety of serious or difficult-to-treat and nosocomially acquired infections in hospitalised and immunocompromised patients. Such infections have included respiratory tract, urogenital tract, and bone and joint infections, septicaemia and surgical infections, in addition to severe Gram-negative infections in neutropenic cancer patients. Pefloxacin demonstrates comparable efficacy with ampicillin combined with gentamicin in upper gynaecological tract infections, ceftazidime in nosocomially acquired Gram-negative infections and co-trimoxazole (trimethoprim + sulphamethoxazole) in uncomplicated urinary tract infections and typhoid fever. Although the place of pefloxacin in this new and expanding class of 4-quinolone antibacterial drugs has yet to be defined and it appears to be a well-tolerated and useful drug for the treatment of serious infections in hospitalised patients, further studies are awaited with interest for confirmation of these preliminary results.     

Enoxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use

Enoxacin is a new addition to the class of 4-quinolone antibacterial drugs. It has a broad spectrum of in vitro antibacterial activity, and is particularly potent against Gram-negative organisms and staphylococci. The pharmacokinetic profile of enoxacin is similar to that of ofloxacin, achieving higher plasma and tissue concentrations and possessing a longer half-life than norfloxacin or ciprofloxacin. In comparative studies, clinical and/or bacteriological efficacy was comparable or (in studies which statistically analysed the results) not significantly different between enoxacin and amoxycillin in acute cystitis, acute Gram-negative exacerbations of chronic bronchitis and acute or chronic otitis media, between enoxacin and cephalexin in skin, skin structure and soft tissue infections, between enoxacin and trimethoprim in acute cystitis, between enoxacin and co-trimoxazole in complicated urinary tract infection and between enoxacin and pipemidic acid in suppurative otitis media. Significantly (p less than 0.01) more clinical and/or bacteriological cures were effected by enoxacin than pipemidic acid in acute cystitis and complicated urinary tract infection. In uncomplicated gonococcal infections single oral doses of enoxacin were effective in over 90% of patients. Enoxacin is a well-tolerated, orally active broad spectrum antibacterial drug which should prove a worthwhile alternative to currently available antibacterial therapy.     

Netilmicin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use

Netilmicin is a semisynthetic aminoglycoside derived from sisomicin. It is active against most Gram-negative and some Gram-positive bacteria, including many gentamicin-resistant strains. Netilmicin has proved to be effective in Gram-negative infections of the urinary tract, skin and skin structure, and lower respiratory tract, as well as in intra-abdominal infections, septicaemia and other miscellaneous infections. In some trials, the more easily implemented once daily administration of netilmicin has been as effective as multiple dosing regimens. However, further investigation is required to confirm that efficacy and safety are not compromised with once daily administration. Comparative studies have generally revealed similar clinical and bacteriological efficacies between netilmicin and gentamicin, amikacin or tobramycin. As with other aminoglycosides, the principal adverse effects of netilmicin are nephrotoxicity and ototoxicity. Although animal studies strongly suggest that these are less common with netilmicin than with related drugs, there appears to be no difference in their incidence in clinical use; in clinical trials the incidence of nephrotoxicity and ototoxicity has been low, with the symptoms in many cases being minor and reversible. Netilmicin is, therefore, an effective antibacterial drug for the parenteral treatment of severe infections, offering theoretical advantages in safety which may indicate its use for patients believed to be at risk of adverse effects.     

Comparative in vitro activity of ciprofloxacin and five other quinoline derivatives against gram-negative isolates

A total of 375 Gram-negative bacterial strains were isolated from midstream urine specimens of the same number of patients affected by urinary tract infections. All bacteria were identified by standard bacteriological methods and their susceptibility to six quinoline derivatives (ciprofloxacin, cinoxacin, norfloxacin, oxolinic acid, pipemidic acid, nalidixic acid) was studied by determining the MICs and MBCs for each compound using a miniaturized dilution broth method in microtitre plates and twofold dilutions of each drug from 256 to 0.12 mcg/ml. Ciprofloxacin, a new quinoline carboxylic acid compound structurally related to nalidixic acid, showed a much higher antibacterial activity against all bacterial strains under examination, including Pseudomonas, than the other compounds, except for norfloxacin. The MIC90 and MBC90 of ciprofloxacin never exceeded 1 mcg/ml with any of the bacterial species; and MBC/MIC ratios were very low, which represents an important clinical advantage. Only norfloxacin showed comparable effectiveness. No bacterial strain showed resistance to the drug and the MIC90 and MBC90 never exceeded 8 mcg/ml.     

Effect of cinoxacin on cellular metabolism and p-aminohippurate transport in kidney cortical slices in terms of its nephrotoxic action

Cinoxacin is a drug which, at very high doses, causes renal damage only in rats. This study compared the in vitro effects of cinoxacin and nalidixic acid on cellular metabolism and p-aminohippurate (PAH) transport in renal cortical slices. Cinoxacin had no effect on Na+ transport, ATP content, oxygen consumption, inulin space and tissue water content, in rat renal cortical slices in vitro, while nalidixic acid affected most of the parameters tested. PAH uptake by slices from rats pre-treated with a nephrotoxic dose of cinoxacin was decreased. This renal damage appeared to be due to physical trauma resulting from deposition of cinoxacin crystals in the urinary tract.     

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.     

Cefotetan. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use

Cefotetan is a new semisynthetic cephamycin antibiotic administered intravenously or intramuscularly. It has a broad spectrum of activity against Gram-negative aerobic and most clinically important Gram-positive and anaerobic bacteria, and is generally more active against Gram-negative bacteria than the 'first and second generation' agents. Cefotetan is particularly active against Enterobacteriaceae but has little activity against Pseudomonas aeruginosa. An extended plasma elimination half-life of about 3.5 hours, and relatively high achievable serum and tissue levels, enables cefotetan to be administered on a twice daily basis in the treatment of mild to severe infections. Cefotetan has shown good clinical efficacy in intra-abdominal, obstetric and gynaecological infections, postoperative wound infections, and infections in immunocompromised patients - all of which are often complicated due to their polymicrobial nature or by the presence of anaerobic pathogens. A satisfactory clinical response is achieved in over 90% of paediatric patients with acute otorhinolaryngological infections, whereas in the treatment of chronic disease, as with other agents, the efficacy is dramatically reduced. Like other cephalosporins, cefotetan is effective in treating patients with complicated urinary tract infections and lower respiratory tract infections. Its efficacy in urinary tract infections is at least as good as cefoxitin, although in this and some other clinical areas its activity relative to that of other cephamycins and cephalosporins remains to be assessed. Thus, with its convenient twice daily dosage schedule, cefotetan would appear to be a useful addition to a rapidly expanding group of antibacterial agents.     

Ceftizoxime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use

Ceftizoxime is a 'third generation' cephalosporin administered intravenously or intramuscularly. Like other third generation cephalosporins it has a wide spectrum of in vitro activity against Gram-positive and Gram-negative bacteria, is particularly active against Enterobacteriaceae (including beta-lactamase-positive strains), and is resistant to hydrolysis by beta-lactamases. However, the third generation cephalosporins are less active than earlier cephalosporins against staphylococci and so could not be considered the drugs of choice. Like many currently available third generation cephalosporins, ceftizoxime has limited activity against Pseudomonas aeruginosa, and thus cannot be recommended as sole treatment of known or suspected non-urinary tract pseudomonal infections. Similarly, although favourable clinical results have been obtained in patients treated with ceftizoxime for infections caused by mixed aerobic/anaerobic organisms (such as intra-abdominal, and obstetric and gynaecological infections), the relatively low in vitro activity of ceftizoxime (in common with most other third generation cephalosporins) against Bacteroides fragilis and enterococci may restrict its usage in situations where these organisms are the suspected or proven pathogens. Ceftizoxime appears to be similar in efficacy to several other cephalosporins in lower respiratory tract infections in elderly and/or debilitated patients, and in chronic and/or complicated urinary tract infections, 2 clinical situations in which third generation cephalosporins may have a major role. Ceftizoxime is also effective clinically and bacteriologically in skin, soft tissue, bone and joint infections, septicaemia/bacteraemia, meningitis and neonatal infections. However, a few large, well designed clinical comparisons of efficacy with aminoglycosides are needed before ceftizoxime can be recommended as an alternative in patients in whom potential aminoglycoside toxicity is a concern. Single intramuscular doses of ceftizoxime appear similar in efficacy to aqueous procaine penicillin G in gonorrhoeae due to nonpenicillinase-producing Neisseria gonorrhoea, and ceftizoxime is also highly effective against penicillinase-producing strains. Although only a few infections have been treated to date, ceftizoxime may be useful in the treatment of gonorrhoea in places where penicillinase-producing strains are common. Thus, ceftizoxime appears to be an effective addition to the growing number of third generation cephalosporins. However, further studies are needed to confirm its relative efficacy compared with other new cephalosporins, in particular cefotaxime.(ABSTRACT TRUNCATED AT 400 WORDS)     

Aztreonam. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use

Aztreonam (azthreonam; SQ 26,776) is the first member of a new class of beta-lactam antibiotics, the monobactams. Aztreonam is selectively active against Gram-negative aerobic bacteria and inactive against Gram-positive bacteria. Thus, in vitro, aztreonam is inhibitory at low concentrations (MIC90 less than or equal to 1.6 mg/L) against Enterobacteriaceae except Enterobacter species, and is active against Pseudomonas aeruginosa, 90% of pseudomonads being inhibited by 12 to 32 mg/L. Aztreonam is inactive against Gram-positive aerobic bacteria and anaerobes, including Bacteroides fragilis. Therefore, when administered alone, aztreonam has minimal effect on indigenous faecal anaerobes. Aztreonam must be administered intravenously or intramuscularly when used to treat systemic infections, since absolute bioavailability is very low (about 1%) after oral administration. Since elimination half-life is less than 2 hours, 6- or 8-hourly administration is used in the treatment of moderately severe or severe infections, although 12-hourly injection is adequate in less severe systemic and some urinary tract infections. Therapeutic trials have shown aztreonam to be effective in Gram-negative infections including complicated infections of the urinary tract, in lower respiratory tract infections and in gynaecological and obstetric, intra-abdominal, joint and bone, skin and soft tissue infections, uncomplicated gonorrhoea and septicaemia. In comparisons with other antibiotics, aztreonam has been at least as effective or more effective than cefamandole in urinary tract infections and similar in efficacy to tobramycin or gentamicin. Where necessary, aztreonam and the standard drug have both been combined with another antibiotic active against Gram-positive and/or anaerobic bacteria. Aztreonam has been effective in eradicating pseudomonal infections in most patients (except in patients with cystic fibrosis), but the inevitably limited number of pseudomonal infections available for study prevents any conclusions as to the relative efficacy of aztreonam compared with other appropriate regimens against these infections. Thus, with an antibacterial spectrum which differs from that of other antibiotics, aztreonam should be a useful alternative to aminoglycosides or 'third generation' cephalosporins in patients with proven or suspected serious Gram-negative infections.     

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.     

Sulbactam/ampicillin. A review of its antibacterial activity, pharmacokinetic properties, and therapeutic use

Sulbactam is a semisynthetic beta-lactamase inhibitor which when combined with certain beta-lactam antibacterials extends their activity against bacteria that are normally resistant to the antibiotic due to production of beta-lactamases. In combination with ampicillin it extends the antibacterial activity of ampicillin to include beta-lactamase-producing strains which are otherwise resistant, including Bacteroides fragilis, and increases the susceptibility of many sensitive strains. Sulbactam is poorly absorbed after oral administration and sulbactam/ampicillin is therefore administered parenterally, although another linked sulbactam-ampicillin compound, sultamicillin, has been developed which is well absorbed after oral administration. The basic pharmacokinetic characteristics of sulbactam after parenteral administration are similar to those of ampicillin. Multiple-dose therapy with sulbactam/ampicillin is clinically and bacteriologically effective in infections of the urinary tract, skin and soft tissue, bones and joints, respiratory tract, ears, nose and throat, as well as intra-abdominal and obstetric and gynaecological infections and septicaemia. In addition, single intramuscular doses of sulbactam/ampicillin administered with oral probenecid are therapeutically effective in gonorrhoea, including infections due to penicillinase-producing and/or ampicillin-resistant Neisseria gonorrhoeae. In the prophylaxis of infectious complications of surgery sulbactam/ampicillin is superior to placebo and appears to be similar in efficacy to several alternative antibacterial regimens. Further studies involving larger numbers of patients are needed to clarify the comparative therapeutic and prophylactic efficacy of sulbactam/ampicillin and alternative antibacterial drugs. Nonetheless, sulbactam/ampicillin improves the therapeutic and prophylactic efficacy of an antibacterial of familiar safety, and must be seen as a worthwhile advance.     

Imipenem/cilastatin. A reappraisal of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy.

Imipenem is an antibacterial agent of the carbapenem class of beta-lactams, with a very broad spectrum of activity that includes most Gram-negative and Gram-positive pathogens, aerobes and anaerobes, and with marked activity against species producing beta-lactamases. It is coadministered with cilastatin, a renal dehydropeptidase inhibitor that prevents renal metabolism of imipenem. As initial monotherapy, imipenem/cilastatin provides effective and well-tolerated treatment of moderate to severe infections in various body systems, including intra-abdominal, obstetric and gynaecological, lower respiratory tract, skin and soft tissue, and urinary tract infections, and also in bacteraemia and septicaemia, and in patients with malignancy-related febrile neutropenia. It is likely to be of particular benefit in cases where bacterial pathogens have not yet been identified, such as in the treatment of serious infections in immunocompromised patients, or in an intensive care setting. Thus, imipenem/cilastatin is effective as initial monotherapy of a variety of infections, including infections in neutropenic patients, with a clear role in empirical treatment of mixed infection.     

Oral ciprofloxacin in refractory gram-negative bacillary infections

The 13 patients included in this series: had chronic Gram-negative bacillary infections that were refractory to prior antibiotic therapy; were unable or unwilling to receive intravenous antibiotics; and had altered host defenses or environmental factors that contributed to persistent infection. Five patients had chronic polymicrobic Gram-negative osteomyelitis, three had urinary tract infections caused by Pseudomonas aeruginosa, two had Pseudomonas skin infections and three had respiratory tract infections with Gram-negative bacilli. The overall bacteriological cure rate for Gram-negative bacilli was four of five osteomyelitis, all three urinary tract infections, both skin infections and one out of three respiratory infections. Secondary infections occurred in two patients with bone infections, one with prostatitis and one with deep seated cellulitis and myonecrosis. Two patients with end-stage lung disease had emergence of resistant strains during therapy. Ciprofloxacin was well tolerated and effective in most of the ambulatory patients with refractory Gram-negative bacillary infection. It appears to be especially promising for Pseudomonas infections of the bone, urinary tract and soft tissue.     

Urinary tract infections in children younger than 5 years of age: epidemiology, diagnosis, treatment, outcomes and prevention

Although the true incidence of urinary tract infections (UTIs) in children is difficult to estimate, they are one of the most common bacterial infections seen by clinicians who care for young children. Except for the first 8 to 12 weeks of life, when infection of the urinary tact may be secondary to a haematogenous source, UTI is believed to arise by the ascending route after entry of bacteria via the urethra. Enterobacteriaceae are the most common organisms isolated from uncomplicated UTI. Infection with Staphylococcus aureus is rare in children without in-dwelling catheters or other sources of infection, and coagulase-negative staphylococci and Candida spp. are associated with infections after instrumentation of the urinary tract. The diagnosis of UTI in young children is important as it is a marker for urinary tract abnormalities and, in the newborn, may be associated with bacteraemia. Early diagnosis is critical to preserve renal function of the growing kidney. A urine specimen for culture is necessary to document a UTI in a young child. Prior to culture, urinalysis may be useful to detect findings supporting a presumptive diagnosis of UTI. The goals of the management of UTI in a young child are: (i) prompt diagnosis of concomitant bacteraemia or meningitis, particularly in the infant; (ii) prevention of progressive renal disease by prompt eradication of the bacterial pathogen, identification of abnormalities of the urinary tract and prevention of recurrent infections; and (iii) resolution of the acute symptoms of the infection. Delay in initiation of the antibacterial therapy is associated with an increased risk of renal scarring. The initial choice of antibacterial therapy is based on the knowledge of the predominant pathogens in the patient's age group, antibacterial sensitivity patterns in the practice area, the clinical status of the patient and the opportunity for close follow-up. Imaging studies to detect congenital or acquired abnormalities are recommended following the first UTI in all children aged <6 years. Patients with significant urinary tract abnormalities and/or frequent symptomatic UTI may benefit from prophylactic antibacterials. The main long term consequence of UTI is renal scarring which may lead to hypertension and end-stage renal disease. Prevention of recurrent UTI focuses on detection, and correction if possible, of urinary tract abnormalities. Interventions that have been associated with a decrease in symptomatic UTI in children with a history of recurrent UTI include relief of constipation and voiding dysfunction.     

Fluorinated quinolones

Quinolones, chemically related to nalidixic acid, have a strong and rapid bactericidal action against Gram-negative bacteria, includingPs. aeruginosa, someMycobacteria, Legionella andStaphylococci. Streptococci and anaerobic bacteria are usually less sensitive. The quinolones exert their bactericidal action through inhibition of the enzyme DNA gyrase. Quinolones are absorbed for 50–100% from the gastro-intestinal tract, their volume of distribution is generally high (2 l/kg) and high concentrations are reached in almost all organs. The elimination half-lives range from 4 to 14 h. The efficacy of quinolones in urinary tract infections has been shown in many studies. They also seem to be effective in many serious infections. In animal studies their efficacy was generally equal or superior to aminoglycosides. Until now only mild and infrequent side effects have been reported.