Ceftriaxone. A review of its antibacterial activity, pharmacological properties and therapeutic use

Ceftriaxone is a new 'third generation' semisynthetic cephalosporin with a long half-life which has resulted in a recommended once daily administration schedule. It is administered intravenously or intramuscularly and has a broad spectrum of activity against Gram-positive and Gram-negative aerobic, and some anaerobic, bacteria. The activity of ceftriaxone is generally greater than that of the 'first' and 'second generation' cephalosporins against Gram-negative bacteria, but less than that of the earlier generations of cephalosporins against many Gram-positive bacteria. Although ceftriaxone has some activity against Pseudomonas aeruginosa, on the basis of present evidence it cannot be recommended as sole antibiotic therapy in pseudomonal infections. Ceftriaxone has been effective in treating infections due to other 'difficult' organisms such as multidrug-resistant Enterobacteriaceae. Ceftriaxone was effective in complicated and uncomplicated urinary tract infections, lower respiratory tract infections, skin, soft tissue, bone and joint infections, bacteraemia/septicaemia, and paediatric meningitis due to susceptible organisms. In most of these types of infections once-daily administration appears efficacious. Results were also encouraging in a few patients with ear, nose and throat, intra-abdominal, obstetric and gynaecological infections, and adult meningitis, but conclusions are not yet possible as to the efficacy of the drug in these indications due to limited experience. A single intramuscular dose of ceftriaxone has been compared with standard therapy for gonorrhoea due to non-penicillinase-producing and penicillinase-producing strains of Neisseria gonorrhoeae and shown to be highly effective. In a few small trials the comparative efficacy of ceftriaxone and other antibacterials has been assessed in other types of infections and in perioperative prophylaxis in patients undergoing surgery. Few significant differences in response rates were found between therapeutic groups in these comparative studies, but larger well-designed studies are needed to more clearly assess the comparative efficacy of ceftriaxone and other antimicrobials, especially the aminoglycosides and other 'third generation' cephalosporins, and to confirm the apparent lack of serious side effects with ceftriaxone. If more widespread use confirms the safety and efficacy of ceftriaxone, it will offer an important alternative, particularly for the treatment of serious infections due to multidrug-resistant Gram-negative bacteria and in situations where the long half-life of the drug could result in worthwhile convenience and cost benefits.     

Cefuroxime: a review of its antibacterial activity, pharmacological properties and therapeutic use.

Cefuroxime is a new semisynthetic cephalosporin for parenteral administration. It is resistant to destruction by beta-lactamases produced by staphylococci and most Gram-negative aerobic bacteria and is active against many bacteria resistant to cephalothin. Cefuroxime is the most active of the cephalosporins against gonococci and Haemophilus influenzae particularly against beta-lactamase producing strains. Given by intramuscular or intravenous injection cefuroxime is effective against a wide variety of infections caused by Gram-positive or Gram-negative aerobes, but has no effect against infections caused by Pseudomonas aeruginosa or B. fragilis. Cefuroxime is of value in the treatment of respiratory infections due to Haemophilus influenzae and Streptocococcus pneumoniae and is useful against cephalosporin-resistant Klebsiella and Enterobacter infections. Cefuroxime is an alternative to spectinomycin for the treatment of beta-lactamase producing Neisseria gonorrhoeae infections. It is generally well tolerated and appears not to be nephrotoxic when given alone at usual dosages.     

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)     

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.     

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.     

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.     

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

Mupirocin (pseudomonic acid A) is a novel topical antibacterial agent which inhibits bacterial protein and RNA synthesis. It has excellent in vitro activity against staphylococci and most streptococci, but has less activity against other Gram-positive and most Gram-negative bacteria. Its rapid systemic metabolism means it will only be used topically which, combined with its novel chemical structure, should make cross-resistance less likely to occur than with other currently available topical antibacterial agents. Mupirocin 2% ointment administered 2 or 3 times daily has shown excellent efficacy in both primary and secondary superficial skin infections, usually with at least 80% of patients being clinically cured or markedly improved, and over 90% eradication of the bacterial pathogen involved. Efficacy in impetigo and, to a somewhat lesser extent, infected wounds has been particularly convincingly demonstrated, while in other secondary skin infections the clinical response seen with mupirocin was often similar to the high success rate of vehicle alone. Limited evidence suggests that mupirocin may be as effective as chlortetracycline, fusidic acid, neomycin and other antibacterial agents, but more controlled, comparative studies are needed. The evidence of efficacy against nasal carriage of Staphylococcus aureus, including methicillin-resistant forms, is encouraging and currently work is being undertaken to improve the acceptability of the vehicle for this use. Side effects are limited to local reactions (in less than 3% of patients) and are no more frequent than observed with the vehicle alone. Thus, mupirocin appears to be a useful addition to the agents available for the treatment of superficial primary skin infections, such as impetigo, although its precise place in therapy remains to be established.     

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

Sultamicillin is the tosylate salt of the double ester of sulbactam plus ampicillin. Sulbactam is a semisynthetic beta-lactamase inhibitor which, in combination with ampicillin, extends the antibacterial activity of the latter to include some beta-lactamase-producing strains of bacteria that would otherwise be resistant. The combination of sulbactam plus ampicillin for parenteral use has previously been shown to be clinically and bacteriologically effective in a variety of infections. The chemical linkage of sulbactam and ampicillin has now produced an orally effective compound, sultamicillin, with antibacterial activity and clinical efficacy which are similar to those of the parenteral formulation. Sultamicillin has been shown to be clinically effective in non-comparative trials in patients with infections of the respiratory tract, ears, nose and throat, urinary tract, skin and soft tissues, as well as in obstetric and gynaecological infections, and in the treatment of gonorrhoea. In a small number of controlled trials, sultamicillin has shown comparable clinical efficacy to phenoxymethyl penicillin (penicillin V) and to amoxycillin (alone and in combination with clavulanic acid) in the treatment of paediatric streptococcal pharyngitis and acute otitis media, respectively; to cefaclor in the treatment of acute otitis media in adults; and to bacampicillin, cloxacillin and flucloxacillin plus ampicillin in skin and soft tissue infections in adults, children and adult diabetic patients, respectively. Sultamicillin was superior in efficacy to bacampicillin in the treatment of chronic respiratory infections, to cefaclor in the treatment of acute otitis media in adults, and to cefadroxil in the treatment of patients with complicated urinary tract infections. However, in single-dose treatment of uncomplicated gonorrhoea, sultamicillin (1500mg plus probenecid 1g) was inferior to a 2g intramuscular dose of spectinomycin. While in several studies the incidence of diarrhoea associated with sultamicillin was greater than that with comparative antibacterials, sultamicillin-associated diarrhoea was generally mild and transitory, although occasionally severe enough to necessitate discontinuation of treatment. Further studies in larger groups of patients are needed to clarify the therapeutic efficacy and safety of sultamicillin in comparison with other antibacterial regimens, and to determine the optimum single dosage for the treatment of gonorrhoea. Nonetheless, sultamicillin appears to provide a similar pharmacodynamic and pharmacokinetic profile to that of parenteral sulbactam plus ampicillin and, as such, will extend the therapeutic efficacy of ampicillin, with the further advantage of allowing treatment of patients with an oral formulation, thus avoiding the potentially adverse clinical and financial effects of prolonged parenteral therapy.     

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.     

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

Ceftazidime is a new 'third generation' cephalosporin administered intravenously or intramuscularly. Similarly to other third generation cephalosporins it has a broad spectrum of in vitro activity against Gram-positive and Gram-negative aerobic bacteria, is particularly active against Enterobacteriaceae (including beta-lactamase-positive strains) and is resistant to hydrolysis by most beta-lactamases. Importantly, in vitro ceftazidime is presently the most active cephalosporin available against Pseudomonas aeruginosa, but it is less active against Staphylococcus aureus than first and second generation cephalosporins. Only larger comparative trials are likely to discern any statistically significant differences in clinical efficacy which may exist between ceftazidime and other antibiotics, but ceftazidime appears to be similar in efficacy to 'standard' comparative drugs in lower respiratory tract infections and complicated and/or chronic urinary tract infections among debilitated or hospitalised patients. Thus, in patients having Gram-negative infections at these sites and in whom the potential toxicity of the aminoglycosides is a concern, ceftazidime may be a valuable alternative in that it apparently lacks serious side effects and does not require routine drug plasma concentration monitoring. In fibrocystic patients having acute respiratory tract infections, ceftazidime is highly effective at both reducing symptoms of infection and temporarily reducing the sputum counts of Pseudomonas species. However, in these patients resistance to ceftazidime may develop, as seen with other beta-lactam antibiotics. In the treatment of fever of unknown origin or documented infections in immunocompromised adults and children, ceftazidime appears to be similar in efficacy to various 2- or 3-drug combinations. Nevertheless, the coadministration of an antibiotic having greater efficacy against Gram-positive bacteria should be considered in immunocompromised patients. Results from a small number of comparative trials suggest that ceftazidime may be as effective as the aminoglycosides in intra-abdominal, obstetric and gynaecological, and skin and soft tissue infections. However, further clinical experience, particularly a few well designed comparative studies, is needed to clarify the comparative efficacy in these conditions as well as in septicaemia/bacteraemia, meningitis, and bone and joint infections.     

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.     

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

Cefmenoxime is an aminothiazolyl cephalosporin administered intravenously or intramuscularly. Like other 'third-generation' cephalosporins it is active in vitro against most common Gram-positive and Gram-negative pathogens, is a potent inhibitor of Enterobacteriaceae (including beta-lactamase-producing strains), and is resistant to hydrolysis by beta-lactamases. Cefmenoxime has a high rate of clinical efficacy in many types of infection and is at least equal in clinical and bacteriological efficacy to several other cephalosporins in urinary tract infections, respiratory tract infections, postoperative infections and gonorrhoea. Cefmenoxime, like latamoxef, cefoperazone and cefamandole, has an N-methyltetrazole side chain at the 3-position of the cephalosporin nucleus and thus possesses the potential for producing hypoprothrombinaemic bleeding and disulfiram-like reactions. However, these reactions have been reported very rarely and the antibacterial is generally well tolerated. It is likely that cefmenoxime will most closely resemble cefotaxime and ceftizoxime in therapeutic profile and usefulness.     

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.     

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.     

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.     

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

The antibacterial efficacy of oral lomefloxacin has been investigated in a wide variety of infections, including respiratory and uncomplicated and complicated urinary tract infections, obstetric, gynaecological, joint, skin, oral, ear, nose, throat and eye infections. It has also been used as an otic solution in patients with otitis media and as an ophthalmic solution in the treatment of eye infections. In clinical trials its efficacy is equivalent to that of other quinolones and it is at least as effective as other antibacterial drugs ordinarily used in these infections. Lomefloxacin offers certain advantages compared with other quinolone antibacterial drugs in that it may be conveniently administered once daily and theophylline dosage adjustment does not appear to be necessary in patients receiving this bronchodilator concomitantly. Thus, orally administered lomefloxacin should prove a useful broad spectrum antibacterial drug for a wide variety of clinical infections.     

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

Cefodizime is a third generation cephalosporin with a broad spectrum of antibacterial activity. Administered intravenously or intramuscularly, cefodizime 1 to 4 g daily for an average of 7 to 10 days produced clinical cure in 80 to 100% of patients (adults, elderly or children) with upper or lower respiratory tract infections or urinary tract infections, and in comparative trials cefodizime was as effective as other third generation cephalosporins. A single dose of cefodizime 1 or 2 g is also useful in treating lower urinary tract infections, particularly uncomplicated infections, with a rate of clinical success of 72 to 88%. Urogenital gonorrhoea, whether caused by beta-lactamase producing or non-beta-lactamase producing Neisseria gonorrhoeae, is very effectively treated by single dose therapy with intramuscular cefodizime 0.25 to 1 g (virtually 100% cured). Preliminary data from a small number of patients indicate that cefodizime may also be useful in the treatment of otitis media, sinusitis and gynaecological infections, and for the prophylaxis or treatment of surgical infections. The clinical efficacy of cefodizime in comparison with other third generation cephalosporins is superior to that predicted from in vitro results. This superior activity of cefodizime may be related to the relatively long elimination half-life of the drug or its ability to modify some functions of the immune system--a potentially important finding awaiting further investigation. Cefodizime is well tolerated and has a tolerability profile similar to other members of its class with systemic adverse events being primarily gastrointestinal or dermatological. Thus, limited comparative studies indicate cefodizime has the potential to become a useful alternative to current antimicrobial therapy for the treatment of a variety of infections. Cefodizime may be more convenient to administer than some other agents of its class as it may be given once or twice daily. While there are no trials comparing cefodizime to other third generation cephalosporins in immunosuppressed populations, preliminary information indicates cefodizime may be useful in this group.     

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.     

Sufentanil. A review of its pharmacological properties and therapeutic use

Sufentanil, an opioid analgesic, is an analogue of fentanyl, and has been used for the induction and maintenance of anaesthesia, and for postsurgical analgesia. It has shorter distribution and elimination half-lives, and is a more potent analgesic than fentanyl. In clinical practice, however, intravenously administered sufentanil produces essentially equivalent anaesthesia to fentanyl and is a better anaesthetic than morphine or pethidine (meperidine) for major surgery. It would appear to maintain haemodynamic stability during surgery better than other opioids or inhalational anaesthetics. Postoperative respiratory depression has been reported in a few patients. For outpatient surgery, intravenous sufentanil produces equivalent anaesthesia to isoflurane or fentanyl. Recovery tends to be more rapid after sufentanil and the requirement for postoperative analgesia is less. Initial clinical trials with sufentanil administered epidurally to relieve pain during labour have produced encouraging results, but further studies are required to establish the drug's role in this indication. Epidural sufentanil produces a more rapid onset and better initial quality of analgesia than morphine, buprenorphine or hydromorphine when administered postoperatively, but the duration of analgesia is shorter. Thus, sufentanil's primary place in therapy at this time would appear to be as high dose anaesthesia for major surgery such as cardiac surgery, and as low dose supplement to balanced anaesthesia in general surgery. In addition, low doses administered epidurally seem to have a potential role for analgesia during labour or after surgery although further studies are required to clarify this situation.     

Milrinone. A preliminary review of its pharmacological properties and therapeutic use

Milrinone is a bipyridine derivative of amrinone, with approximately 10 to 75 times greater positive inotropic potency, and separate direct vasodilatory properties. As with amrinone, the relative importance of these properties to treatment of congestive heart failure still remain controversial. The mode of action of milrinone appears to be due in part to selective inhibition of a specific cardiac phosphodiesterase with a subsequent increase in intracellular cyclic adenosine monophosphate and alteration in intracellular and extracellular calcium transport. Clinical experience has involved both short and long term treatment of a limited number of patients with moderate to severe congestive heart failure refractory to conventional therapy. Milrinone has usually been administered as intravenous bolus doses (12.5 to 75 micrograms/kg) and/or continuous intravenous infusion (0.5 microgram/kg/min), or orally (30 to 40 mg/day in divided doses). Milrinone rapidly improves cardiac performance by enhancing myocardial contractility, and by decreasing systemic vascular resistance (afterload), left ventricular filling pressure (preload), and pulmonary arterial pressure. Exercise performance improvement occurs with enhancement of left ventricular performance but without a significant increase in myocardial oxygen consumption or significant decrease in mean arterial pressure. Milrinone has been compared with dobutamine, nitroprusside and captopril in preliminary short term studies in patients with severe congestive heart failure. Milrinone significantly increased stroke work index and decreased left ventricular filling pressure compared to nitroprusside. When compared with dobutamine, both drugs improved cardiac index (to a similar degree), but milrinone significantly reduced right atrial pressure, pulmonary capillary wedge pressure and left ventricular end-diastolic pressure. One small study suggests that short term effects of intravenous milrinone may be superior to those of oral captopril, and it appears that the addition of captopril to milrinone therapy may produce a synergistic haemodynamic effect. Preliminary long term studies suggest that tolerance to the haemodynamic effects of milrinone does not occur, and that the drug is well tolerated and without the thrombocytopenic effects, fever and gastrointestinal complications observed with amrinone. However, it has not been demonstrated that milrinone improves the prognosis of the disease or the overall mortality and its propensity to produce arrhythmias has not been fully agreed upon.(ABSTRACT TRUNCATED AT 400 WORDS)