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.     

Cefotaxime. An update of its pharmacology and therapeutic use

Cefotaxime was the first 'third generation' cephalosporin to be marketed and is administered intramuscularly or intravenously. Similar to other agents of this class, it has a broad spectrum of in vitro activity, particularly against Enterobacteriaceae, including beta-lactamase-producing strains. Cefotaxime forms a metabolite, desacetylcefotaxime, which is antibacterially effective against many bacteria per se and acts additively or synergistically with cefotaxime against many strains. Since the first review of cefotaxime in the Journal, further studies have confirmed its value in the treatment of various infections: complicated urinary tract infections, lower respiratory tract infections, bacteraemia, meningitis, uncomplicated gonorrhoea, infections of skin and soft tissue and of bone and joints, and obstetric and gynaecological infections. Cefotaxime is effective as an empirical treatment of suspected infection due to susceptible organisms in immunocompromised patients and is of proven efficacy in serious, life-threatening infections in general. Cefotaxime reduces the incidence of postsurgical infection but the role of third generation cephalosporins in prophylaxis remains to be determined. The indications for which cefotaxime and other 'third generation' cephalosporins would be considered the most appropriate therapy remain largely dependent upon such factors as varied as cost, local medical custom, decisions of regulatory agencies and geographical patterns of bacterial resistance. Cefotaxime nevertheless represents a valuable 'third generation' cephalosporin of great clinical value in certain infectious conditions, in particular those which are serious and life-threatening and where resistance to therapies is creating a clinical problem.     

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

Synopsis: Cefotaxime is a new 'third generation' semisynthetic cephalosporin administered intravenously or intramuscularly. It has a broad spectrum of activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria, and is generally more active against Gram-negative bacteria than the 'first' and 'second generation' cephalosporins. Although cefotaxime has some activity against Pseudomonas aeruginosa, on the basis of present evidence it cannot be recommended as sole antibiotic therapy for pseudomonal infections. However, cefotaxime has been effective in treating infections due to other 'difficult' organisms, such as multidrug-resistant Enterobacteriaceae. Like other cephalosporins, cefotaxime is effective in treating patients with complicated urinary tract and lower respiratory tract infections, particularly pneumonia caused by Gram-negative bacilli. High response rates have also been achieved in patients with Gram-negative bacteraemia. Although favourable clinical results have been obtained in patients with infections caused by mixed aerobic/anaerobic organisms (such as peritonitis or soft tissue infections), the relatively low in vitro activity of cefotaxime against Bacteroides fragilis may restrict its usage in situations where this organism is the suspected or proven pathogen. In preliminary studies, males and females treated with a single intramuscular dose of cefotaxime for uncomplicated gonorrhoea caused by penicillinase-producing strains of Neisseria gonorrhoeae responded very favourably. Encouraging results have also been reported in open studies in children including neonates, treated with cefotaxime for meningitis and various other serious infections. In some situations, cefotaxime has been given in combination with another antibiotic such as an aminoglycoside, but the merits of such a combination have not been clearly established. Whether cefotaxime alone is appropriate therapy for conditions previously treated with aminoglycosides (other than pseudomonal infections) also needs additional clarification, but if established as equally effective in such conditions cefotaxime offers potentially important clinical and practical advantages in its apparent lack of serious adverse effects and freedom from the need to undertake drug plasma concentration monitoring.     

Ceftizoxime: a beta-lactamase-stable, broad-spectrum cephalosporin. Pharmacokinetics, adverse effects and clinical use

Ceftizoxime is an iminomethoxy aminothiazolyl cephalosporin that inhibits a wide variety of aerobic, anaerobic gram-positive and gram-negative bacteria. The majority of Enterobacteriaceae are inhibited by less than or equal to 1 microgram/ml as are streptococcal species with the exception of Streptococcus faecalis. Staphylococcus aureus are inhibited by 3-8 micrograms/ml, while methicillin-resistant. aureus are resistant. Bacteroides fragilis are inhibited by 16-64 micrograms/ml. It inhibits Pseudomonas aeruginosa at usually achievable concentrations. Ceftizoxime is overall similar in antibacterial activity to cefotaxime and moxalactam. Ceftizoxime is not hydrolyzed by common plasmid and chromosomal beta-lactamases. Serum levels of ceftizoxime after intramuscular and intravenous injection are similar to those of cefotaxime and moxalactam. The half-life is 1.6 to 1.9 hours in normal individuals. The compound is not metabolized and is cleared from the body by glomerular filtration. Ceftizoxime enters most body fluids, including the cerebrospinal fluid, to produce therapeutic concentrations against clinically important bacteria. Ceftizoxime accumulates in the presence of renal failure, but it is removed from the body by hemodialysis and peritoneal dialysis. Ceftizoxime has proved to be an effective chemotherapeutic agent when used as treatment for pneumonia, urinary tract infections, osteomyelitis, septic arthritis, meningitis, peritonitis, gonorrhea, including penicillinase-producing isolates, and gynecological infections. No major adverse reactions have been associated with the use of ceftizoxime and it has produced neither disulfram -like reactions nor bleeding.     

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.     

阴沟肠杆菌感染的临床分布与耐药性分析

目的了解阴沟肠杆菌的临床分布状况及耐药性,为临床治疗阴沟肠杆菌的感染提供参考。方法用WHONET5.4统计软件回顾性分析阴沟肠杆菌的分布及抗菌药物耐药性状况。结果 2006年1月至2009年6月共分离出233株阴沟肠杆菌,菌株来源主要为痰液、尿液、伤口分泌物,分别占24.9%、19.3%、14.2%;阴沟肠杆菌对碳青酶烯类、阿米卡星、头孢吡肟、头孢唑肟、哌拉西林/他唑巴坦的敏感性较高。结论阴沟肠杆菌主要引起呼吸道、尿道和创伤感染;对三代头孢菌素耐药严重,呈多药耐药性,亚胺培南、四代头孢菌素仍为治疗阴沟肠杆菌严重感染的首选用药。     

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.     

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.     

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.     

Use of cephalosporins with enhanced anti-anaerobic activity for treatment and prevention of anaerobic and mixed infections

The microbiology, adverse-effect profiles, pharmacokinetics, published results of comparative clinical trials, and costs of cephalosporins with enhanced antianaerobic activity are reviewed. Cefoxitin, ceftizoxime, cefotetan, and moxalactam have been used as single agents in the treatment or prophylaxis of anaerobic or mixed aerobic and anaerobic infections, including intra-abdominal, female genital tract, and soft-tissue infections. None of these agents is as active against Bacteroides species as is clindamycin or metronidazole, but differences among the four cephalosporins do not appear to be clinically important. These agents differ somewhat in their activity against gram-positive and gram-negative bacteria. The majority of adverse reactions to these agents are immunological; disulfiram-like reactions and alterations in normal hemostasis have also been observed with cefotetan and moxalactam. All of these agents are well absorbed after intramuscular injection and produce serum concentrations adequate to treat most infections. Only ceftizoxime and moxalactam produce cerebrospinal fluid concentrations adequate for treatment of gram-negative meningitis. The primary route of elimination is renal, and each agent requires dosage adjustments in patients with renal impairment. Major differences exist among the elimination half-lives of the agents in patients with normal renal function. The decision to use a cephalosporin for treatment of anaerobic infections should be based on the results of clinical trials that have demonstrated the efficacy of the agent. Data are available to support the use of cefoxitin, ceftizoxime, and moxalactam in the treatment of intra-abdominal infections; cefoxitin and moxalactam to prevent infection of traumatic injury to the abdomen; all four agents in the treatment of female genital tract infections; and all four agents for prophylactic use in surgical procedures that may involve enteric anaerobes, especially B. fragilis. Cephalosporins with enhanced antianaerobic activity appear to have similar in vitro microbiological activity and have efficacy similar to that of combination regimens for the treatment and prophylaxis of intra-abdominal infections, abdominal contamination, obstetric and gynecological infections, and soft-tissue 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.     

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.     

头孢唑肟与其他5种抗生素体外抗菌活性比较

目的　比较头孢唑肟与其他 5种抗生素对临床分离菌的体外抗菌活性。方法　用 NCCL S2 0 0 2年发布的琼脂平板法测定抗生素的最低抑菌浓度。结果　本研究共测定细菌 5 70株 ,其中革兰氏阴性菌 36 7株 ,革兰氏阳性菌 2 0 3株。头孢唑肟对肠杆菌科细菌与链球菌具有强大抗菌活性 ,大肠埃希氏菌、肺炎克雷伯氏菌、产气肠杆菌、志贺氏菌、奇异变形菌、摩根摩氏菌、流感噬血杆菌、肺炎链球菌、化脓链球菌、无乳链球菌、粘膜炎莫拉氏菌对头孢唑肟 10 0 %敏感。头孢唑肟对大多数肠杆菌科细菌 MIC值与头孢曲松相近 ,远低于头孢他啶和头孢呋辛。头孢唑肟对液化沙雷氏的菌抗菌活性为所有检测药物中最强的一个 ,MIC50 与 MIC90 均为0 .5 mg/ L。结论　头孢唑肟应用于临床 15年后仍保持强大抗菌活性 ,本品可用于中重度细菌感染的经验性治疗     

Ceforanide. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy

Ceforanide is a 'second generation' cephalosporin administered intravenously or intramuscularly. It is similar to cefamandole and cefonicid in its in vitro superiority to 'first generation' cephalosporins against several species of Enterobacteriaceae as well as its activity against Haemophilus influenzae, including beta-lactamase-producing strains. Its activity against Staphylococcus aureus is less than that of cefamandole, cefuroxime and first generation cephalosporins. The in vitro activity against Neisseria gonorrhoeae is excellent. Pseudomonas, Acinetobacter and Serratia species, and Bacteroides fragilis are resistant, as are many strains of Proteus and Providencia species. The elimination half-life is relatively long, although shorter than that of cefonicid, and in most clinical trials ceforanide has been administered twice daily. It appeared to be comparable in therapeutic efficacy to procaine penicillin and cephazolin in the treatment of patients with community-acquired pneumonia, to cephazolin in the treatment of skin and soft tissue infections due to S. aureus or beta-haemolytic streptococci and to cefapirin in S. aureus endocarditis in parenteral drug abusers. Also, it was comparable in efficacy to cephalothin in the prophylaxis of infection in patients undergoing open heart surgery or vaginal hysterectomy, and to cephazolin in patients undergoing cholecystectomy. Thus, ceforanide is an alternative to first and certain other second generation cephalosporins in several important therapeutic and prophylactic situations. It has no advantage over other cephalosporins with regard to spectrum of antibacterial activity, but has a longer half-life than other second generation cephalosporins, except cefonicid, and can be administered according to a twice daily dosage schedule.     

头孢唑肟钠与维生素B6注射液存在配伍禁忌

头孢唑肟钠为第三代头孢菌素,在与维生素B6注射液联合应用时存在配伍禁忌。因此,临床应用时两药不宜在同一输液器内接触,以确保患者用药安全。     

Clinical pharmacokinetics of the third generation cephalosporins

At the present time, the third generation cephalosporins that are already on the market or close to this point include cefsulodin, cefotaxime, cefoperazone, latamoxef, ceftriaxone, ceftazidime, ceftizoxime and cefotetan. Other newer compounds are also under development but have not been included in this review. None of the third generation compounds is suitable for oral administration and, accordingly, their pharmacokinetics have been studied only after intravenous and intramuscular administration. Microbiological assays and HPLC methods have been used for the measurement of plasma/serum, urine, bile and cerebrospinal fluid (CSF) concentrations. As found with cefotaxime, microbiological assays should only be used when the full metabolite spectrum of a particular drug is known, as otherwise, the presence of microbiologically active metabolites may lead to erroneous conclusions. Under normal conditions, the major route of elimination is via the kidneys for cefsulodin, latamoxef, ceftazidime, ceftizoxime and cefotetan. In contrast, cefoperazone is mainly eliminated in the bile, whereas cefotaxime and ceftriaxone depend both on the liver and the kidneys for their elimination. With the exception of ceftriaxone, which has a longer elimination half-life (i.e. around 8 hours), all the other third generation cephalosporins have a t1/2 ranging between 1.5 and 2.5 hours. Plasma protein binding is variable from one compound to another. However, the clinical relevance of this parameter is not clearly established since tissue penetration also depends on the relative affinity of the drug for tissue components. Third generation cephalosporins seem to penetrate adequately into the CSF and, thus pharmacokinetically appear to be appropriate agents for the treatment of meningitis. The degree of modification of pharmacokinetic parameters by renal insufficiency or hepatic diseases depends, as for other drugs, on the extent to which the compound is excreted via the kidneys or the liver. The third generation cephalosporins have been extensively studied under these conditions and recommendations for dosage modification in special circumstances are available for most of them. The pharmacokinetics of some third generation cephalosporins may be modified in neonates and elderly patients. Accordingly, their use at the extremes of age must be accompanied by a closer than usual clinical monitoring of the patient. From a clinical point of view, the third generation cephalosporins possess reliable pharmacokinetic properties.(ABSTRACT TRUNCATED AT 400 WORDS)     

Moxalactam (latamoxef). A review of its antibacterial activity, pharmacokinetic properties and therapeutic use

Moxalactam (latamoxef) is a new synthetic oxa-beta-lactam antibiotic administered intravenously or intramuscularly. It has a broad spectrum of activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria, is particularly active against Enterobacteriaceae and is resistant to hydrolysis by beta-lactamases. Moxalactam has moderate activity against Pseudomonas aeruginosa, but on the basis of present evidence can not be recommended as sole antibiotic treatment of known or suspected pseudomonal infections. Like the related compounds, the cephalosporins, moxalactam is effective in the treatment of complicated urinary tract infections and lower respiratory tract infections caused by Gram-negative bacilli. As moxalactam is also active against Bacteroides fragilis it has considerable potential in the treatment of intra-abdominal infections in patients with normal immunological mechanisms, as well as in immunocompromised patients, when used alone or in combination with other antibiotics. Likewise, its ready penetration into the diseased central nervous system, its high level of activity against Gram-negative bacilli, and the lack of necessity to monitor drug plasma concentrations, indicate its potential value in the treatment of neonatal Gram-negative bacillary meningitis. Further clinical experience is needed before it can be determined whether moxalactam alone can be used in the treatment of conditions for which the aminoglycosides are drugs of choice, but if established as equally effective, moxalactam has the advantage of being devoid of nephrotoxicity. Bleeding is a potentially serious problem, however, particularly in the elderly, malnourished and in the presence of renal impairment.     

Effectiveness of ceftizoxime on various infections in patients with underlying diseases

Ceftizoxime (CZX), a parenteral cephalosporin derivative belonging to the so-called third generation cephalosporin is reported to have a broad antibacterial activity, particularly against Gram-negative aerobic bacilli and some anaerobes, such as Bacteroides fragilis and a good stability to beta-lactamases. Clinical study was performed on a total of 20 cases, 9 females (1 case had urinary tract infection 3 times) and 11 males, aged from 27 to 82 years. All patients had the underlying diseases. They were bronchial asthma in 3 cases, influenza in 1, chronic pulmonary emphysema in 1, pulmonary fibrosis in 1, chronic bronchitis with strongyloidiasis in 1, lung cancer in 3, esophagus cancer in 2, stomach cancer in 1, hepatoma with urolithiasis in 1, liver cirrhosis with diabetes mellitus in 1, alcoholism with strongyloidiasis in 1, cholelithiasis in 1 and congestive heart failure in 1, respectively. Clinical diagnoses for infections were 2-acute bronchitis, 2-exacerbation of chronic bronchitis, 2-broncho-pneumonia, 2-pneumonia including one suspected case, 1-obstructive pneumonia, 2-secondary pulmonary infection, 1-pulmonary infection, 3-urinary tract infection (UTI), 1-UTI with sepsis, 1-sepsis, 1-sepsis with purulent meningitis, 1-biliary tract infection and 1-infected bronchoesophageal fistula. CZX was given by intravenous drip infusion, at a dose of 1 to 2 g, twice daily for 3 to 15 days. Because of severity in infections and underlying diseases, some cases were treated either steroid, gamma-globulin preparations or other antibiotics in combination with CZX. Twelve out of 15 cases assessed clinically responded satisfactorily to the treatment and efficacy rate was 80.0%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Current concepts in the management of gonorrhoea

The incidence of gonorrhoea is again rising in developed countries and a high disease rate has been maintained in less developed regions for a number of years. The need not only for treatment of the individual but also for control of gonorrhoea at a community level has increased significantly following recognition of its role in the amplification of human immunodeficiency virus (HIV) transmission. A sustainable decrease in the incidence of gonorrhoea and other sexually transmitted diseases (STDs) requires an integrated approach combining improved prevention, better diagnosis and optimal treatment. Effective antibiotic treatment is an essential element of this approach. However, antibiotic treatment of gonorrhoea has been severely hampered by the development of antibiotic resistance in Neisseria gonorrhoeae, to the extent that many therapies are no longer effective. Those treatments that retain acceptable efficacy are often unaffordable where they are most needed. Penicillins and tetracyclines should no longer be used in gonococcal disease, there are limitations on the effectiveness of newer macrolides and spectinomycin and in many parts of the world quinolones have been withdrawn from schedules for the treatment of gonorrhoea. Of all the current agents used to treat all forms of gonococcal disease, only the third generation cephalosporins (most notably ceftriaxone) have retained their efficacy; however, decreased susceptibility to these antibiotics has also appeared. Continuing reliance on antibiotic treatment for controlling gonorrhoea in the absence of other necessary approaches will see a further deterioration in the situation. In these circumstances the possibility that gonorrhoea will be untreatable becomes more real.     

Current concepts in the management of gonorrhoea

The incidence of gonorrhoea is again rising in developed countries and a high disease rate has been maintained in less developed regions for a number of years. The need not only for treatment of the individual but also for control of gonorrhoea at a community level has increased significantly following recognition of its role in the amplification of human immunodeficiency virus (HIV) transmission. A sustainable decrease in the incidence of gonorrhoea and other sexually transmitted diseases (STDs) requires an integrated approach combining improved prevention, better diagnosis and optimal treatment. Effective antibiotic treatment is an essential element of this approach. However, antibiotic treatment of gonorrhoea has been severely hampered by the development of antibiotic resistance in Neisseria gonorrhoeae, to the extent that many therapies are no longer effective. Those treatments that retain acceptable efficacy are often unaffordable where they are most needed. Penicillins and tetracyclines should no longer be used in gonococcal disease, there are limitations on the effectiveness of newer macrolides and spectinomycin and in many parts of the world quinolones have been withdrawn from schedules for the treatment of gonorrhoea. Of all the current agents used to treat all forms of gonococcal disease, only the third generation cephalosporins (most notably ceftriaxone) have retained their efficacy; however, decreased susceptibility to these antibiotics has also appeared. Continuing reliance on antibiotic treatment for controlling gonorrhoea in the absence of other necessary approaches will see a further deterioration in the situation. In these circumstances the possibility that gonorrhoea will be untreatable becomes more real.