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Background: Recent analysis of clinical data and a clearer understanding of the role of chemical structure in the development of cross-reactivity indicate that the increased risk of an allergic reaction to a cephalosporin in penicillin-allergic patients is smaller than previously postulated., Method: Medline and EMBASE databases were searched with the keywords: cephalosporin, penicillin, allergy, and cross-sensitivity for the years 1960 through 2005. Among 219 articles retrieved, 9 served as source material for this evidence-based meta-analysis., Results: A significant increase in allergic reactions to cephalothin (odds ratio [OR] = 2.5; 95% confidence interval [CI] = 1.1 to 5.5), cephaloridine (OR = 8.7; CI = 5.9 to 12.8), and cephalexin (OR = 5.8; CI = 3.6 to 9.2), and all first generation cephalosporins plus cefamandole (OR = 4.8; CI = 3.7 to 6.2) were observed in penicillin allergic patients; no increase was observed with second generation cephalosporins (OR = 1.1; CI, 0.6 to 2.1) or third generation cephalosporins (OR = 0.5; CI = 0.2 to 1.1). Clinical challenges, skin testing, and monoclonal antibody studies point to the paramount importance of similarities in side chain structure to predict cross-allergy between cephalosporins and penicillins., Conclusion: First-generation cephalosporins have cross-allergy with penicillins, but cross-allergy is negligible with second- and third-generation cephalosporins. Particular emphasis should be placed on the role of chemical structure in determining the risk of cross-reactivity between specific agents.

A 87-year-old patient developed coagulation abnormality following hip surgery related to the prophylactic use of cefamandole. Cefamandole as others cephalosporins with a methyl-tetrazol-thiol lateral chain interferes with the vitamin K regeneration cycle as do oral anticoagulants. Therefore, the use of others antibiotics or systematic vitamin K1 supplementation or single dose of cefamandole is recommended for patients with renal failure or with malnutrition. Vitamin K1 supplementation is a simple method resulting in complete resolution of the coagulation disorder.

In a randomized prospective study ampicillin/sulbactam and cefamandole were compared in the therapy of patients hospitalized with community acquired pneumonia. Patients receiving ampicillin/sulbactam (n = 37) and cefamandole (n = 38) were similar with respect to age (mean age 70 vs. 76 years respectively), clinical characteristics, severity of illness and underlying disease. Pathogens isolated from patients in the cefamandole and ampicillin/sulbactam group, respectively, were Streptococcus pneumoniae (7 vs. 7 patients), Haemophilus parainfluenzae (7 vs. 6 patients), Haemophilus influenzae (5 vs. 5 patients), Staphylococcus aureus (5 vs. 4 patients), Escherichia coli (4 vs. 4 patients), Klebsiella pneumoniae (3 vs. 3 patients), Enterobacter spp. (2 vs. 3 patients), Moraxella catarrhalis (1 vs. 2 patients), and organisms of the oral flora (4 vs. 3 patients). The rate of resistance to penicillin was 80%, to clindamycin 76%, to erythromycin 45%, to ampicillin 43%, and to cefazolin 18%. Overall successful treatment rates of 81% for cefamandole and 97% for ampicillin/sulbactam (p = 0.05) were observed. Both cefamandole and ampicillin/sulbactam were shown to be effective agents for therapy of community acquired pneumonia; however ampicillin/sulbactam demonstrated superior overall clinical efficacy.

Three-hundred twenty-one adults undergoing cardiac or major vascular operations were randomized to receive intravenous cefazolin, cefamandole, or vancomycin for prophylaxis against surgical infection in a double-blind trial. All three regimens provided therapeutic blood levels throughout operation in patients studied undergoing cardiopulmonary bypass. The prevalence of surgical wound infection was lowest with vancomycin (4 infections [3.7%] versus 14 [12.3%] and 13 [11.5%] in the cefazolin and cefamandole groups, respectively; p = 0.05); there were no thoracic wound infections in cardiac operations in the vancomycin group (p = 0.04). The mean duration of postoperative hospitalization was lowest in the vancomycin group (10.1 days; p < 0.01) and highest in the cefazolin group (12.9 days). Prophylaxis with vancomycin or cefamandole, compared with cefazolin, did not prevent nosocomial cutaneous colonization by methicillin-resistant coagulase-negative staphylococci; colonization or infection with vancomycin-resistant staphylococci or enterococci was not detected. Adverse effects attributable to the prophylactic regimen were infrequent in all three groups. Eight patients given vancomycin became hypotensive during administration of a dose, despite infusion during a 1-hour period; however, slowing the rate of administration and pretreating with diphenhydramine allowed vancomycin to be resumed and prophylaxis completed uneventfully in five of the patients. We conclude that administration of vancomycin (approximately 15 mg/kg), immediately preoperatively, provides therapeutic blood levels for surgical prophylaxis throughout most cardiac and vascular operations, resulting in protection against postoperative infection superior to that obtained with cefazolin or cefamandole. Vancomycin deserves consideration for inclusion in the prophylactic regimen (1) for prosthetic valve replacement and prosthetic vascular graft implantation, to reduce the risk of implant infection by methicillin-resistant coagulase-negative staphylococci and enterococci; (2) for any cardiovascular operation if the patient has recently received broad-spectrum antimicrobial therapy; and (3) for all cardiovascular operations in centers with a high prevalence of surgical infection with methicillin-resistant staphylococci or enterococci. Guidelines for dosing and administration of vancomycin for cardiovascular surgical prophylaxis are provided.

Antibiotics can be associated with hypoprothrombinaemic haemorrhages in risk patients. Risk factors are: poor nutrition, impaired liver- or renal function, coagulation depleting medical therapy or illness. Pathogenetically there is a vitamin K deficiency with reduction of vitamin K dependent clotting factors; mainly by decreased vitamin K synthesis in intestinal bacterias. In consequence every risk patient under antibiotics should receive vitamin K prophylactically and in a parenteral way, because of unreliable resorption in gastrointestinal tract. Prothrombin-time-monitoring is essential to recognize the hypoprothrombinemia in every risk patient under antibiotics.

We report 4 cases in which the use of cephamandole was associated with coagulopathy. All 4 patients had renal impairment, but no other known predisposing factors. It is recommended that the coagulation profile be monitored during administration of cephamandole, especially when there is a background of renal impairment.

This study determined the pharmacokinetic disposition of cefonicid. A single dose of 7.5 mg/kg of body weight was administered to five healthy volunteers as a 5-min intravenous infusion. Multiple plasma and urine samples were collected for 48 h. Peak plasma concentrations ranged from 95 to 156 micrograms/ml and fell slowly (mean plasma half-life, 4.4 +/- 0.8 h), so that levels after 12 h were in the range of 6 to 12 micrograms/ml. Urinary concentrations were high but variable and ranged from 100 to 1,000 micrograms/ml for the first 12 h after the dose and averaged 84 micrograms/ml between 12 and 24 h. Plasma and renal clearances were 0.32 +/- 0.06 and 0.29 +/- 0.05 ml/min per kg, respectively. An average of 88 +/- 6% of the dose was excreted unchanged in the urine over 48 h. The mean steady-state volume of distribution was found to be 0.11 +/- 0.01 liters/kg.

Osteomyelitis of the pubic bone due to anaerobic bacteria has been reported infrequently, although an entity known as "sterile" osteitis pubis is common to the literature. We have described two cases of pubic osteomyelitis due to anaerobic bacteria, discussed two previously reported cases, and suggested that most cases of what has previously been termed sterile osteitis pubis may actually have been due to anaerobic bacteria that were not isolated because of deficiencies in collection, transport, and culture of clinical specimens. Included are the pathogenesis and an approach to the treatment of this entity.

Cefamandole nafate has been shown to have good in vitro activity against a wide spectrum of aerobic and anaerobic pathogens frequently isolated from women with obstetrical and gynecological infections. One hundred and twenty seven women with these infections were treated with cefamandole: 78 had post-cesarean section metritis; 24 acute pelvic inflammatory disease; 18 post-hysterectomy cuff cellulitis/abscess; and 7 had vulvar or abdominal wound abscesses. All but 13% of these women had either polymicrobial aerobic/anaerobic bacterial infections, or had an anaerobic infection alone. Of these 127 women, 116 responded to cefamandole administration alone, and in the other 11 chloramphenicol was added. Of these 11, surgical therapy was necessary to eradicate infection in six women. Phlebitis, mild to severe, was demonstrated in 14% of the women and responded to conservative measures. Of 402 bacterial isolates from these women, 94% were sensitive to cefamandole at 32 microgram/ml, an easily achievable serum level. Anaerobic streptococci were the most common isolate and 94% of these organisms were sensitive at 32 microgram/ml. Of the 43 Bacteroides species isolated, 90% were susceptible at 32 microgram/ml; 84% of Bacteroides fragilis were susceptible ast this concentration. Data now presented indicate that cefamandole given alone is safe and effective for treatment of women with polymicrobial mixed aerobic/anaerobic pelvic infections and approximately 5% will require surgical therapy for eradication of these infections.

In a randomized, prospective clinical trial cefamandole therapy was compared with cefamandole plus amdinocillin in infants and children with suspected bacterial infections. Fifty-two infections in 50 patients with bone and joint (19 infections), pulmonary (19 infections), soft tissue (eight infections), and urinary tract (6 infections) diseases were treated. Bacterial infection was documented in 31 patients. All isolates were susceptible to cefamandole except one strain of Serratia marcescens, which was susceptible to the combination. In vitro synergy was demonstrated in all coliform bacilli, in three of seven Haemophilus strains, and in six of 16 gram-positive cocci. No correlation between degree of serum bactericidal activity and presence or absence of synergy could be demonstrated. One patient treated with cefamandole died; all other patients responded promptly to therapy without serious adverse drug effects.

Since the introduction of cephalothin and cephaloridine as the first parenteral cephalosporins and cephalexin as the first member of the group which is absorbed from the gastrointestinal tract, several new cephalosporin derivatives have been developed. Most of these have no major advantages over cephalothin, cephaloridine or cephalexin. Increased knowledge about the importance of beta-lactamases for bacterial resistance against beta-lactam antibiotics has focused interest on development of drugs with increased resistance to degradation by these enzymes. Among the caphalosporins, cefamandole and cefuroxime have been found to be markedly more active against beta-lactamase producing Gram-negative bacteria. A new group of beta-lactam antibiotics, the cephamycins, have been introduced with cefoxitin as the first clinically useful member. Cefoxitin has the spectrum of a beta-lactamase-resistant cephalosporin and is also active against Bacteroides fragilis. The review concentrates on the antibacterial spectrum of these three new antibiotics and on their clinical efficacy.

A double-blind, multicenter trial compared cefonicid and cefazolin for prophylaxis against postoperative infection in 117 patients undergoing joint replacement. Cefonicid, which has an extended serum half-life, was administered once daily, while cefazolin was given every eight hours. The drug was administered one half to one hour before surgery and continued for up to 72 hours. Patients were observed throughout their hospitalization period and followed for 30 days after discharge. No evidence of wound or joint infection was observed in any of the patients who met the criteria for evaluation. Adverse reactions consisted mainly of infrequent gastrointestinal symptoms and laboratory abnormalities. Three patients died from causes unrelated to study medication. No differences between the two regimens were found with respect to safety or efficacy in the prevention of postoperative infection after arthroplasty. The effectiveness of once-daily administration should make cefonicid a highly cost-effective alternative to many of the more expensive first- and second-generation cephalosporin antibiotics currently used in hospital practice.

One hundred seven patients with community-acquired pneumonia thought to be of bacterial etiology by the admitting physician but whose initial sputum Gram stain was inadequate to direct specific therapy were randomized to receive either intravenous ampicillin or cefamandole as empiric therapy. Patients were excluded if the initial sputum Gram stain was highly suggestive of infection with Streptococcus pneumoniae, Staphylococcus aureus, or an enteric gram-negative bacillus. The two study groups had comparable demographic and presenting clinical features. The mean age of the patients evaluable for determination of clinical efficacy was 69 years, and greater than 75% had at least one serious underlying medical disorder. In the 90 evaluable patients, there were 11 therapeutic failures (12%), including 5 deaths (5%). Cefamandole, a broad-spectrum antibiotic, was not more efficacious than ampicillin in producing a satisfactory clinical response or in shortening the duration of parenteral therapy. Patients received an average of only 4 days of intravenous antibiotics before changeover to oral therapy and were hospitalized for a mean of 7 days. No patient experienced a relapse of pneumonia following successful completion of parenteral drug therapy. We conclude that cefamandole is not a more effective agent than ampicillin for empiric therapy of community-acquired bacterial pneumonia of uncertain etiology.

The aim of this study was to compare the effects of the prophylactic use of cefamandole versus oxacillin plus gentamicin on hemostasis in patients undergoing hip replacement with heparin prophylaxis. Twenty-four patients with a normal hemostatic profile were randomly allocated to receive either cefamandole or oxacillin plus gentamicin. All the patients received calcium heparin. Platelet count, bleeding time, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin clotting time (TCT), fibrinogen and serum FDP were assessed before treatment and every day of antibiotic administration. Surgical bleeding was assessed using a four-grade score system. Platelet count, bleeding time, fibrinogen and serum FDP did not show any change with both treatments. PT, aPTT and TCT showed a similar and mild prolongation in the two groups of patients. No difference in the surgical bleeding was observed between the two groups. We conclude that a short-term prophylaxis with cefamandole is a safe regimen in patients undergoing hip replacement with heparin prophylaxis.

Twenty patients with skin and soft-tissue infections were treated with parenteral cefonicid. Cultures obtained in cellulitis cases from an aspirate of a leading edge of inflammation were positive in 42% of these patients. Pathogens isolated were Staphylococcus aureus (six strains), Proteus mirabilis (one strain), and Streptococcus agalactiae. Adverse effects were pain on intramuscular injection (two patients), rash (one patient), and positive Coombs test (one patient). All side effects were mild and none required discontinuing antibiotic therapy. A single treatment failure occurred in a patient with an undrained perirectal abscess. Cefonicid may be a useful drug in the treatment of skin and soft-tissue infections. The long half-life of cefonicid (4.8 h) is a valuable advantage and may facilitate patient compliance and convenience.

A combination of tobramycin sulfate and cefamandole nafate was used as initial empiric therapy for the treatment of 71 evaluable febrile (temperature greater than 38.5 degrees C) episodes in 64 (neutrophils, less than 1,000/microL) adult patients with cancer and granulocytopenia. Carbenicillin sodium or ticarcillin disodium was substituted for cefamandole in patients with Pseudomonas infections and in patients in whom the initial regimen was unsuccessful. Twenty-nine episodes were randomized to receive tobramycin by continuous infusion, while 42 were randomized to receive tobramycin by interrupted infusion. Twenty-seven (79%) of the 34 documented infections responded to the initial empiric antibiotic combination, ten (83%) of 12 being given continuous infusion and 17 (77%) of 22 being given interrupted infusion of tobramycin. Nephrotoxic reaction occurred in 7% of patients treated with continuous infusion and 15% treated with interrupted infusion, mostly patients older than 60 years. Tobramycin, by either continuous or interrupted infusion, plus cefamandole is safe and efficacious empiric therapy for infections in patients with cancer and granulocytopenia.

Cefonicid is a new second-generation cephalosporin with a broad antimicrobial spectrum of activity and a prolonged serum elimination half-life. It has good in vitro activity against methicillin-sensitive Staphylococcus aureus, nonenterococcal streptococci, Hemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis and many of the commonly isolated Enterobacteriaceae. Organisms usually resistant to cefonicid include species of Pseudomonas, Serratia, Acinetobacter and Providencia, and Bacteroides fragilis. The drug is 98% protein bound in human serum, which probably contributes to its significant reduction of antimicrobial activity measured in serum. Limited clinical trials have demonstrated it to be effective for surgical prophylaxis and for treating infections of the urinary tract, lower respiratory tract and bone. Failures have been reported in treatment of soft tissue infections and endocarditis caused by S. aureus. A potential cost reduction may be achieved by administering a single daily dose of cefonicid for established infections or a single preoperative dose for effective surgical prophylaxis instead of multiple-dose regimens of other, similar agents.

Cefamandole was evaluated as the sole antimicrobial agent used to treat bacterial peritonitis in 113 patients. Dosage varied between 1 and 2 g given intravenously every 6 hr. Laparotomy for excision of infected or gangrenous tissues, closure of gastrointestinal perforations, or drainage of an established abscess was required in 99 of the cases. A good clinical response was obtained in 107 patients, or 95% of the total group. Of the six deaths only one could be attributed to infection. No evidence of renal, hepatic, or hematopoietic toxicity was noted. There were no allergic reactions, although 13 patients (12%) developed phlebitis in a vein used for antibiotic administration. Bacteriological studies revealed aerobic peritonitis in 99% of the patients, with anaerobe participation in 60% of these cases. Sensitivity testing by the disk diffusion and tube dilution methods confirmed the appropriateness of cefamandole therapy; 91% of the gram-negative rods and 61% of the anaerobes were susceptible. From results of this study, it would appear that cefamandole is a reliably effective antibiotic for use in treatment of most forms of acute peritonitis. Its role in surgical prophylaxis may be even more promising.

Fifty-nine community-acquired pneumonias were treated in a randomized double blind trial with cefamandole or ceftazidime. A prospective scoring system was used to define severity. This made use of basic clinical data, associated diseases, white blood count, blood gases and chest radiographs. There were no serious side-effects from the drugs. There were two deaths and six failed treatment. The scoring system which defined an 'ill group' showed as good a response of these ill patients to the new cephalosporin, ceftazidime as to cefamandole.

A review is made of the pharmacological, biochemical and chemical aspects of the unpleasant 'Antabuse-like' reaction that may be induced in drinkers of alcohol by pre-treatment with certain beta-lactam antibiotics with a 1-methyltetrazole-5-thiol sidechain (such as moxalactam, cefamandole and cefoperazone). The symptoms are due to abnormally elevated blood acetaldehyde levels consequent upon the inactivation of hepatic aldehyde dehydrogenase. There is very little direct effect of the antibiotics on this enzyme and therefore it is concluded that a reactive metabolite of the antibiotics' essential sidechain is responsible for the reaction. A likely candidate for this active species is either the symmetrical disulphide 5,5'-dithiobis(1-methyltetrazole) formed by oxidation of 1-methyltetrazole-5-thiol, or the related mixed disulphide, methyl 5-(1-methyltetrazolyl) disulphide. The first of these is a potent inactivator of cytoplasmic aldehyde dehydrogenase only, the second affects both cytoplasmic and mitochondrial isoenzymes. 1-Methyltetrazole-5-thiol or derivatives have the potential to be used therapeutically as 'anti-alcohol' compounds in the same way as disulfiram (Antabuse) or calcium cyanamide.

Ceftazidime and cefamandole were compared in the treatment of pneumonia. The median MIC of ceftazidime for all Streptococcus pneumoniae (n = 17) and Haemophilus influenzae (n = 10) isolates was 0.125 microgram/ml. All other isolates were inhibited by less than 0.5 microgram of ceftazidime per ml, with the exception of a group B streptococcus (MIC = 4 micrograms/ml). Satisfactory clinical responses were observed in 91% (20 of 22) of cefamandole-treated patients and 85% (17 of 20) of ceftazidime-treated patients.

In a single blind study we compared the efficacy of aztreonam (Az), a novel monocyclic beta-lactam antibiotic, to that of cefamandole (Cef) in the treatment of serious urinary tract infections (UTIs). Twenty-one patients were studied (6 men and 15 women, 18-75 years old), 12 suffering from an upper and 9 from a lower UTI; 14 of them received Az and 7 Cef (2:1 ratio), according to a prospective randomization schedule. Az or Cef were administered intramuscularly (1 g every 8 hours) for 5 to 10 days. Patients were followed up for 28 to 42 days after end of treatment. The following bacteria were isolated in the urine cultures: E. coli (in 14 cases), Proteus sp. (4), Klebsiella sp. (2) and Pseudomonas sp. (in 1 case). All 21 bacterial isolates were susceptible to Az while 19 of them were susceptible to Cef (the Pseudomonas strain was sensitive to Az but resistant to Cef). During the entire period of observation, we had 13 cures and 1 relapse in Az-group and 5 cures and 2 relapses in the Cef-group. Aztreonam was as equally well tolerated as cefamandole and no major side effects were observed in either group. In 4 Az- and 3 Cef-patients a rise of SGOT and SGPT (up to 2 1/2 times the upper normal limits) was observed, but it subsided a few days after the end of treatment. Our study shows that aztreonam is at least as effective, safe and well tolerated an antimicrobial agent for the treatment of serious urinary tract infections as cefamandole; In the future aztreonam deserves a large scale, systematic trial in all infections caused by gram-negative bacteria.

Thirty-one adult patients with infections due to anaerobic bacteria were treated with cefamandole. Bacteroides fragilis group (17) and Bacteroides melaninogenicus (13) were the most frequent anaerobes isolated. Duration of therapy varied from 2 to 49 days. Results were judged satisfactory in 26 cases, and unsatisfactory in 1 case. Four cases could not be evaluated. Adverse reactions occurred in 16 patients and included positive direct Coombs' test without hemolysis, transient liver function abnormalities, phlebitis, reversible neutropenia, fever, eosinophilia, and toxic epidermal necrolysis. The more significant reactions were associated with prolonged therapy. None was lethal. These data suggest that cefamandole is effective in treatment of most anaerobic infections.

Cefamandole nafate (CM) and cephalothin sodium (CP) were administered as prophylaxis in a randomized, prospective study to 30 consecutive patients undergoing prosthetic cardiac valve insertion. A single dose of 20 mg/kg was given intramuscularly during anesthesia induction, and serial plasma antibiotic concentrations, atrial muscle and cardiac valve tissue antibiotic levels, plasma bactericidal activity against pathogenic staphylococci, and infectious complications were determined and compared for the two drugs. Both antibiotics produced high plasma levels (>20 mug/ml 30 min after injection) which fell less than 25% during the period of cardiopulmonary bypass. However, CM levels were significantly higher at most time periods (P<0.05) than CP levels. CP levels were undetectable in atrial muscle from 14 of 15 patients and in valves from 10 of 15 patients. In contrast, CM bioactivity was found in all tissues. Differences in tissue antibiotic concentration could not be accounted for by differences in plasma concentrations or by CP tissue binding and were assumed to be caused by differences in penetration. Plasma bactericidal activity against staphylococci was equal for the two drugs (median titer, 1:16). No infections were seen in either group. CM appeared to be an effective and perhaps preferable prophylactic antibiotic for use during cardiac surgery.

One hundred and five patients with penetrating abdominal injuries were treated with single-antibiotic regimens. Forty-seven patients were treated with intravenous (IV) cefamandole and for comparison 58 patients were treated with IV carbenicillin previously shown to be effective against postoperative infections associated with abdominal trauma. The overall incidence of deep infection on a single antibiotic therapy was 8.6 per cent, including two patients on cefamandole alone (4.3%) and seven (12.1%) on carbenicillin alone. One in each antibiotic group died of sepsis with a total mortality of 1.9 per cent. The authors concluded that cefamandole when used alone was found to be safe and more effective than carbenicillin alone in preventing sepsis in patients with abdominal trauma.

We conducted a prospective, randomized, double-blind comparison of intravenous penicillin and cefamandole in the therapy of pneumococcal pneumonia. Patients received either 1 g of cefamandole or 600,000 U of aqueous penicillin G every 6 h. Of the 100 patients entered into the study, 96 had clinical and radiographic evidence of pneumonia. Microbial etiology was determined from the results of sputum and blood cultures and/or sputum Gram stains. Streptococcus pneumoniae was pathogenic in 49 patients, of whom 24 received cefamandole and 25 received penicillin. There was no statistically significant difference in the response or cure rate. Of the 100 patients, 93 were treated for 3 days or more and were evaluated for adverse effects and toxicity. There was no significant difference between cefamandole-treated and pencillin-treated patients in the incidence of colonization, superinfection, phlebitis, thrombocytosis, decrease in hematocrit, or elevated liver function tests. Eosinophilia occurred more frequently in patients treated with penicillin (20 of 42) than in those treated with cefamandole (11 of 42 (chi square, P < 0.05). Only one patient receiving cefamandole developed a positive direct Coombs test. No patient in either group developed meningitis. We conclude that, with the doses and route of administration employed in this study, cefamandole is as effective as penicillin in the therapy of pneumococcal pneumonia without an increased incidence of colonization, superinfection, or adverse effects.

Eighty-two adult hospitalized patients suffering from respiratory tract infections were treated with cefotiam or cefamandole in an open comparative study. The patients were allocated randomly to one of the two treatments. The recommended dosage regimens (i.m. or i.v.) were used for both groups (cefotiam 1 g b.i.d., cefamandole 1 g t.i.d.). The duration of treatment was 7 to 14 days according to the response of the disease condition. 80 patients were analyzed. The tolerability of both drugs was good and comparable. The clinical and bacteriological efficacy of both drugs was equivalent. The radiological examinations showed a better improvement of the patients treated with cefotiam.

Fifty-seven children, ages 1 month to 17 years, were treated with parenteral ceforanide. Most patients received 20 mg/kg of the drug intramuscularly every 12 hours. The mean duration of ceforanide therapy was 6.3 days (range, 3 to 14 days). Because ceforanide has a relatively long half-life of 1.94 +/- 0.43 hours (range, 1.1 to 3.3 hours), suprainhibitory plasma concentrations against most pathogens recovered from the study patients were maintained for 8 to 12 hours after a dose. Ceforanide diffused well into abscess cavities and joint fluid. Initial clinical response was satisfactory in all patients; however, one patient with Haemophilus influenzae type b bacteremia had relapse of bacteremia one week after ceforanide therapy. Ceforanide was well-tolerated with minimal pain at the site of intramuscular injections. Other side effects were minor and transient.

To assess the possibility that non-aminoglycoside antibiotics may adversely affect the nephrotoxicity of the new semisynthetic aminoglycoside netilmicin, we gave ampicillin, carbenicillin, methicillin, cefamandole, and clindamycin, either singly or in combination with netilmicin, at two dose concentrations in rats. Results were compared as to the effect of netilmicin given singly and to saline-injected and noninjected controls. Antibiotic combinations resulted in no greater nephrotoxicity than did netilmicin alone. Netilmicin concentrations in renal tissue were high, and these levels were not consistently affected by the other drugs. The data suggest that in rats the nephrotoxicity of netilmicin is not affected adversely by the presence of non-aminoglycoside antibiotics.

Ceftazidime and cefamandole were compared in a randomized multicentre trial in hospitalized patients with pneumonia. Of 290 patients enrolled, 92 patients in the ceftazidime group and 71 patients in the cefamandole group were evaluable. Geometric mean MICs of organisms isolated and tested to ceftazidime were within achievable therapeutic serum concentrations of ceftazidime. Satisfactory clinical responses were observed in 91% (84/92) of ceftazidime-treated patients and 83% (59/71) of cefamandole-treated patients (P greater than 0.05). Superinfection occurred in one (1%) ceftazidime-treated patient and in five (7%) cefamandole-treated patients. Side effects were infrequent with either treatment. Ceftazidime is as safe and effective as cefamandole for the treatment of pneumonia due to a variety of Gram-positive and Gram-negative pathogens.

The safety and efficacy of treatment with cefamandole were evaluated in 30 patients (from 18 institutions) with serious bone and joint infections. Five of the subjects were children. The antibiotic was given intramuscularly or intravenously in doses ranging from 2 to 12 g daily for five to 44 days. Twenty-six of the 30 patients responded satisfactorily. Fourteen of the fifteen infections due to Staphylococcus aureus were among the successful cases. Other pathogens were streptococci, Escherichia coli, Proteus mirabilis, and Bacteroides fragilis. The drug was well tolerated in patients in this series. Studies indicated that cefamandole penetrated the bones and joints. Further investigation of cefmandole in the treatment of bone and joint infections is warranted.