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This report presents the pooled results from two randomized trials of lomefloxacin and cefotaxime used as prophylaxis in patients undergoing transurethral surgical procedures. A total of 499 patients were enrolled at seven centers in the United States. Patients received either 400 mg of lomefloxacin orally 2-6 hours prior to surgery, or 1 g of cefotaxime intravenously or intramuscularly 30-90 minutes preoperatively. Patients undergoing simple cystoscopy or retrograde pyelograms were not eligible for inclusion. Urine cultures were obtained prior to surgery, 24 hours post-surgery, prior to catheter removal, and 3-5 days post operatively. Treatment failure was defined as isolation of greater than or equal to 10(5) colony-forming units (CFU)/mL of pathogenic bacteria from any post-surgical urine culture. Lomefloxacin was successful in preventing post operative infections in 204 of 207 evaluable patients (98.6%); there were three prophylactic failures. Cefotaxime was successful in 196 of 206 (95.1%) evaluable patients; 10 were prophylactic failures. Lomefloxacin concentrations were measured simultaneously in serum and in samples of prostate tissue from 29 patients undergoing transurethral resection of the prostate. Lomefloxacin prostate concentrations were 1.0-22.3 micrograms/g, with a mean of 5.0 micrograms/g. The average tissue:plasma ratio was 2.0. The safety profile of the two study drugs was excellent, and both were well tolerated. Adverse events were reported by 12.7% of the patients treated with lomefloxacin and 13.8% of those treated with cefotaxime. The majority of events were mild and required no treatment.

Third-generation cephalosporins are important additions to the range of antibiotics available for treating children with serious bacterial infections. They are highly active against the common pathogens, which cause bacterial meningitis in children. Strains of Haemophilus influenzae type b resistant to both ampicillin and chloramphenicol, and Streptococcus pneumoniae relatively resistant to penicillin remain susceptible to cefotaxime and ceftriaxone. Escherichia coli, Klebsiella pneumoniae, Citrobacter diversus, as well as the other more common gram-negative bacilli isolated from neonates and children are susceptible to these agents. However, Listeria monocytogenes is not cephalosporin-sensitive. Ceftazidime is the only third-generation cephalosporin useful for treating serious infections due to Pseudomonas aeruginosa in children. As with other beta-lactam antibiotics, the clearance of cephalosporins is prolonged in neonates, particularly premature babies. Cefotaxime and ceftriaxone are equivalent to ampicillin and chloramphenicol for the treatment of bacterial meningitis in children over two to three months of age with respect to neurologic outcome and safety, despite the in vitro activity of cefotaxime and ceftriaxone being much greater than the standard antibiotics for the meningeal pathogens. Cefotaxime and ceftriaxone are effective in the treatment of serious gram-negative infections in children. In many instances, ceftriaxone can be administered once daily, which allows for more convenient therapy, particularly on an outpatient basis. Although controversial, ceftazidime has been used as single-agent therapy for empiric treatment of neutropenic immunocompromised children with fever.

Cefotaxime, a third-generation cephalosporin, is active against many troublesome gram-negative organisms and anaerobes that now more frequently cause nosocomial infection. Single-dose cefotaxime, 1 g or 2 g administered 30 minutes prior to surgery, has been proven to be effective as prophylaxis for infection following gastrointestinal, biliary, obstetric, gynecologic, and genito-urinary procedures. When published trials are compiled, single-dose cefotaxime is more effective than multiple-dose cefazolin (p less than 0.01) in these types of surgery. Unfortunately, the dramatic increase in cephalosporin use has been accompanied by the emergence of resistant organisms such as enterococci and fungi. In Europe, some centers successfully prevent nosocomial pneumonia in intubated patients by decontaminating gastric contents with a combination of nonabsorbable antimicrobial agents including cefotaxime. Further trials may validate this concept for use in the United States.

Nephrotoxicity frequently complicates the use of aminoglycosides in severely compromised acute care patients. Therefore, an open clinical trial was initiated to determine if cefmenoxime alone is useful in serious nosocomial pneumonias. Thirty consecutive patients were entered in the trial, and 28 patients with an average age of 66 years were evaluable. Most were malnourished at entry, with serum albumin averaging 2.8 g/dl and prognostic nutritional index values over 70 percent (normal less than 40 percent). One-half the patients had severe chronic obstructive pulmonary disease and 68 percent required ventilators. Fifty-seven percent had concomitant cardiac disease, and 79 percent had previously been treated with antibiotics. Pneumonia was proven to be present by new infiltrate on chest x-ray, new fever, elevated white blood cell count, and gram-negative rods on gram stain and in cultures of tracheal aspirates or sputum. Patients were given cefmenoxime 1 to 2 g every six hours an average of 12 days. Cefmenoxime peak (one hour) and trough concentrations were measured by high pressure liquid chromatography and averaged 58 and 7 micrograms ml, respectively. Pharmacokinetic data in 18 patients were determined from serum profiles. Gram-positive organisms, Escherichia coli, Klebsiella, and Hemophilus influenzae were usually eradicated. Persistence was noted for some Enterobacter, Pseudomonas, Serratia, and Acinetobacter. Persistence in patients with good clinical response was considered colonization rather than superinfection. Overall, a satisfactory clinical response rate was noted in 78.6 percent of evaluable patients, whereas four patients responded satisfactorily with recurrence and two treatments had an unsatisfactory response. No serious adverse effects were observed. Cefmenoxime is a promising agent in the treatment of susceptible pneumonias in critical care patients.

Fifty-nine patients with serious infections were assigned at random in a two-to-one ratio to receive either cefmenoxime or cefoxitin given intravenously in a dosage of 0.5 to 2.0 g every six hours. Of 44 patients evaluable for efficacy, eight had concomitant bacteremia and all but 10 had serious underlying disease. The average duration of therapy was seven days. All patients with skin and soft tissue infections were cured after treatment with either antibiotic. Cefmenoxime achieved clinical and bacteriologic cures in 92 and 83 percent, respectively, of 12 patients with pneumonia and in 100 and 82 percent of 11 patients with urinary tract infections. Cefoxitin therapy resulted in clinical and bacteriologic cures in all four patients with pneumonia. Among 10 patients with urinary tract infection, respective cure rates were 90 and 50 percent. Both antibiotics were well tolerated. One cefmenoxime-treated patient discontinued treatment because of a rash.

A randomized trial to compare the efficacy and safety of 1 g of ceftriaxone daily and 3 to 4 g of cefazolin daily was conducted in 84 hospitalized adults with skin and soft tissue infections. A variety of infections including bacteriologically proven cellulitis, suppurative diabetic foot ulcer, soft tissue abscess, and other miscellaneous infections were treated. Side effects were minimal. Colonization with various microorganisms was observed during therapy with both agents. Clinical cure with or without surgery was achieved in 81 percent (34) of 42 patients treated with ceftriaxone and 77 percent (32) of 42 patients treated with cefazolin. The major difference between antibiotics was the rate of failure in infections caused by multiple organisms: five failures among 13 patients treated with cefazolin compared with no failures among 12 patients treated with ceftriaxone. Ceftriaxone appears to be an effective agent when given once daily as therapy for many serious skin and soft tissue infections.

Cefotaxime is a cephalosporin active against most gram-positive and gram-negative organisms, including streptococci, Staphylococcus aureus, Enterobacteriaceae, Proteus, and many Pseudomonas and Bacteroides fragilis--all but the latter two are inhibited at concentrations below 0.5 micrograms/ml. We evaluated cefotaxime as the sole therapy for 32 infections in 31 patients. Infection sites included 18 bacteremias; pulmonary, urinary tract, deep tissue infections; and meningitis. Clinical cures were achieved in 88 percent and bacteriologic cures in 86 percent of the patients--including those with infections due to organisms resistant to cephalosporins, chloramphenicol, carbenicillin and aminoglycosides; and in two patients with meningitis due to multiresistant Klebsiella pneumoniae. Serum and cerebrospinal levels were readily maintained above the inhibitory levels of susceptible organisms. Adverse reactions were minimal. Cefotaxime was a safe, effective antibiotic in the treatment of infections due to susceptible organisms, including those resistant to other agents.

In this 31-site multicenter trial, 565 adult patients with urinary tract infections were randomly assigned to receive either a 10-day course of cefixime 400 mg once daily (n = 279) or amoxicillin 250 mg three times daily (n = 286). Although all patients were included in the safety analysis, only 93 (33 percent) cefixime-treated and 99 (35 percent) amoxicillin-treated patients were fully evaluable for the efficacy analysis. One week after therapy, the evaluable patients treated with cefixime demonstrated a 90 percent clinical cure rate and a 92 percent eradication rate of the baseline pathogen. This compared with an 83 percent clinical cure rate and an 84 percent bacterial eradication rate in the amoxicillin-treated group. The most frequently isolated pathogen was Escherichia coli (80 percent) followed by Proteus mirabilis (10 percent). One hundred thirty-seven (49 percent) of the 279 cefixime-treated and 126 (44 percent) of the 286 amoxicillin-treated patients reported at least one adverse experience during the study. Adverse reactions associated with cefixime were similar to those reported for other beta-lactam antibiotics. The most frequent adverse experiences reported by cefixime-treated patients were diarrhea (15 percent) and stool changes (12 percent). Headaches (11 percent) and diarrhea (9 percent) were the most frequently reported adverse reactions by the amoxicillin-treated patients. Eleven cefixime-treated patients (3.9 percent) and 10 amoxicillin-treated patients (3.5 percent) discontinued therapy because of adverse experiences. Results of this study demonstrate that a once-daily regimen of cefixime is as safe and effective as a three-times-daily regimen of amoxicillin in the treatment of acute urinary tract infections. Although the incidence of bowel changes was somewhat higher in the cefixime treatment group, these events usually resolved when therapy was discontinued.

Of 66 episodes of pneumococcal meningitis seen in Bellvitge Hospital, Barcelona, Spain (January 1981 to June 1987), 15 (23 percent) were due to penicillin-resistant pneumococci [minimal inhibitory concentrations (MICs) of 0.1 to 4 micrograms/ml]. Fifty percent of these strains were also resistant to chloramphenicol. Most were sporadic community-acquired cases. Clinical characteristics were similar in both penicillin-resistant and penicillin-sensitive cases. Those cases with MICs of greater than 1 microgram/ml did not show a response to penicillin therapy. Of nine patients treated with cefotaxime (200 to 350 mg/kg per day) with penicillin G MICs of 0.1 to 4 micrograms/ml and cefotaxime MICs of less than or equal to 0.03 to 1 microgram/ml, seven recovered, one experienced a relapse after 14 days of therapy and the infection was cured with intravenous vancomycin, and one patient died with sterile cerebrospinal fluid. Thus, adults with meningitis due to penicillin-resistant pneumococci may be adequately treated with high doses (around 300 mg/kg per day) of intravenous cefotaxime if MICs of penicillin G are less than or equal to 4 micrograms/ml. Cases with higher resistance may require another antibiotic such as vancomycin.

To determine if aminoglycoside use and liver disease interact to cause an increased risk for renal dysfunction, data from 179 hospitalized patients who had been enrolled in a prospective, randomized trial of nafcillin/tobramycin versus cefotaxime were analyzed. The cefotaxime-treated patients served as a control group not receiving an aminoglycoside. Renal dysfunction occurred in seven of 88 (8 percent) given cefotaxime and 37 of 91 (41 percent) given tobramycin (p less than 0.001), in 11 of 29 (38 percent) with liver disease and 33 of 150 (22 percent) without liver disease (p less than 0.08), and occurred in 11 of 15 (73 percent) with both liver disease and tobramycin use and in 0 of 14 (0 percent) with liver disease and cefotaxime use (p less than 0.001). By logistic regression analysis, the relative odds of renal dysfunction developing during tobramycin treatment in a patient were 6.0 (95 percent confidence interval: 3.8 to 9.5). The relative odds of renal dysfunction developing in a patient receiving tobramycin and having liver disease were 31.8 (95 percent confidence interval: 19.7 to 51.4). This analysis demonstrates an interaction between tobramycin use and liver disease for increasing the risk of renal dysfunction.

A prospective, double-blind, randomized study of hospitalized patients with skin and skin structure infections was conducted to compare orally administered ciprofloxacin and conventional intravenous cefotaxime therapy. Fifty-six patients, predominantly elderly women, were randomly assigned to receive either ciprofloxacin (24 patients, 25 infected sites) or cefotaxime (32 patients, 36 sites). Patients in the ciprofloxacin group received 750 mg of orally administered ciprofloxacin every 12 hours plus a placebo infusion while the other group received 2.0 g of cefotaxime intravenously every eight hours plus a placebo tablet every 12 hours. The average duration of treatment was seven to 10 days, with a maximum of 21 days. Clinical response per infected site in the ciprofloxacin group was as follows: resolution in 88 percent, improvement in 8 percent, and failure in 4 percent. In the cefotaxime group, there was resolution in 69 percent, improvement in 25 percent and failure in 6 percent. Bacteriologic response per site in the ciprofloxacin group was eradication in 88 percent and persistence in 12 percent. With cefotaxime there was 69 percent eradication, 3 percent marked reduction, 6 percent recurrence, and 22 percent persistence. Clinical and bacteriologic responses were combined using an algorithm to derive a cure rate, which was 91 percent for ciprofloxacin and 61 percent for cefotaxime (p = 0.0214).

The clinical and bacteriologic efficacy of ceftriaxone given once or twice daily was evaluated in 153 studies. A total of 2,635 patients received ceftriaxone given intramuscularly or intravenously, 930 received comparative antibiotics, and 81 received placebo. For the 10 major categories of infections treated (central nervous system, upper and lower respiratory tract, intraabdominal, skin and skin structure, bone and joint, urinary tract, gynecologic, and bacterial sepsis), the clinical response rates were 89 percent or greater. Bacteriologic cure rates were 84 percent or greater overall and 90 percent or greater for seven of 10 categories. Ceftriaxone achieved a satisfactory clinical response (cure or improvement) for 89 (intraabdominal) to 99 percent (urinary tract) of the infections treated. Additionally, pediatric central nervous system infections responded to twice-daily ceftriaxone injection; ceftriaxone, in a single dose as low as 250 mg, cured gonorrhea, and a single dose of ceftriaxone was as effective as multiple doses of cefazolin in surgical prophylaxis.

Ceftriaxone given once-a-day was compared with cefazolin given three times daily as therapy for complicated and uncomplicated urinary tract infections. One hundred ten patients were randomly assigned to receive either 1 g of ceftriaxone every 24 hours or 1 g of cefazolin every eight hours. Standard bacteriologic methods were used to identify the pathogens and their susceptibilities before treatment and at intervals during and after treatment. Clinically, the two regimens were similarly efficacious. Bacteriologic results were significantly better with ceftriaxone in both the proportion of pathogens eradicated and the number of patients cured. The results demonstrate that ceftriaxone compares favorably with cefazolin and is effective when given once-a-day for both complicated and uncomplicated urinary tract infections.

Ceftriaxone possesses potent activity, both in vitro and in vivo, against a broad range of bacteria. MIC50 and MIC90 geometric means were calculated using the results of broth and agar dilution assays performed worldwide. The MIC90 for ceftriaxone overall was 8 micrograms/ml or less for Enterobacteriaceae and 0.024 microgram/ml or less for Neisseria and Hemophilus species. Moderate activity was noted against Pseudomonas and Acinetobacter species (MIC50 12 to 28 micrograms/ml). Ceftriaxone was extremely active against nonenterococcal streptococci (MIC90 0.07 microgram/ml or less) and quite active against methicillin-susceptible Staphylococcus aureus (MIC90 5 micrograms/ml or less). Ceftriaxone generally was inactive against enterococci and methicillin-resistant staphylococci. Activity against anaerobes was good, except for many strains of Bacteroides fragilis and B. thetaiotaomicron (MIC greater than 64 micrograms/ml). Ceftriaxone exhibited excellent stability to beta-lactamases. The effect of medium and inoculum on in vitro testing was minimal. Excellent activity was demonstrated in vivo. Against Enterobacteriaceae, nonenterococcal streptococci, and H. influenzae, the PD50 in mice generally was less than 1 mg/kg. S. aureus strains responded moderately (mean PD50 6.5 mg/kg), whereas against most P. aeruginosa strains, PD50s ranged from 5 to greater than 250 mg/kg. The superior pharmacokinetic profile of ceftriaxone compared with that of other new cephalosporins was demonstrated by use of a prophylactic treatment schedule. The ability of ceftriaxone to penetrate the cerebrospinal fluid and provide excellent therapeutic coverage was confirmed in experimental meningitis models.

Intravenous ciprofloxacin has been investigated in the treatment of serious infections, including those of the urinary tract. In this double-blind, randomized study, its effectiveness as a prophylactic agent in men undergoing transurethral surgical procedures was compared with that of another intravenous agent, cefotaxime. One hundred six men with genitourinary tract obstruction were enrolled in the study. The 102 men evaluable for determination of efficacy (53 in the ciprofloxacin group and 49 in the cefotaxime group) received a single intravenous infusion of either 300 mg ciprofloxacin or 1,000 mg of cefotaxime prior to resection of the prostate for benign prostatic hypertrophy and prostatic carcinoma or internal urethrotomy for urethral stricture. A mean of 32.1 and 40.3 minutes for the ciprofloxacin and cefotaxime groups, respectively, elapsed between the end of the intravenous infusion and the onset of surgery; all but one patient in the ciprofloxacin group underwent catheterization after surgery, of which the mean duration was 3.7 days for both groups. At the time of hospital discharge, patients were evaluated clinically; 50 patients in the ciprofloxacin group (94 percent) and 45 in the cefotaxime group (92 percent) had no bacteriologic evidence of genitourinary tract infection. At follow-up two to six weeks after surgery for the patients with no bacteriologic evidence of genitourinary tract infection, fewer patients in the ciprofloxacin group (8 percent) than in the cefotaxime group (16 percent) remained without evidence of infection. Both drugs were well tolerated. This study demonstrated that a single intravenous dose of ciprofloxacin was as effective as a single dose of cefotaxime in reducing the incidence of infection following transurethral surgical procedures.

Experience with the use of first-generation cephalosporins in bacterial meningitis has been disappointing; low concentrations were obtained in the cerebrospinal fluid, and therapeutic failures were encountered. Of the second-generation cephalosporins cefamandole, cefuroxime, and cefoxitin, only cefuroxime has proved efficacy in meningitis caused by meningococci, pneumococci, or Hemophilus influenzae. The third-generation cephalosporins offer new advantages in the treatment of meningitis because they are active at the cerebrospinal fluid concentrations obtainable. Cefotaxime has produced high cure rates in patients with meningitis caused by meningococci, pneumococci, or H. influenzae. Several controlled comparative studies indicate that ceftriaxone is as effective as conventional treatment in therapy for neonatal or childhood meningitis caused by Streptococcus agalactiae, Escherichia coli, or H. influenzae. Moxalactam has been found in uncontrolled studies to be effective when the cause was enteric gram-negative bacilli. Ceftazidime is a new cephalosporin with a high degree of beta-lactamase stability and a broad antibacterial spectrum, which includes Pseudomonas aeruginosa that enters the cerebrospinal fluid. Data from 29 patients who received ceftazidime as monotherapy for bacterial meningitis showed an overall cure or improvement rate of 75.9 percent. Therapy failed in three patients with meningitis caused by gram-positive organisms (Staphylococcus aureus, S. epidermidis, S. agalactiae), and in three with gram-negative organisms. Of 14 patients with Pseudomonas meningitis, 11 showed a cure, as did six of six patients with meningitis caused by Enterobacter, Serratia, or Acinetobacter. More, preferably controlled, studies of the efficacy of ceftazidime in the treatment of meningitis should be undertaken.

A comparative study was conducted using cefmenoxime, a new extended spectrum cephalosporin, versus cefoxitin. Entry into the study was based on a computer-generated randomization (two cefmenoxime to one cefoxitin). An intravenous dose of cefmenoxime (0.5 to 1 g every six hours) or cefoxitin (1 to 2 g every six hours) was administered to patients suspected of having serious bacterial infections. Six patients had urinary tract infections. Four who received cefmenoxime, including two with positive blood cultures, had eradication of bacteremia. One of the two who received cefoxitin had significant bacteriuria, and the urine was clear after treatment. Twenty-four patients were treated for lower respiratory tract infections. All 15 patients who received cefmenoxime had clinical and bacteriologic cures. Two of the nine patients who received cefoxitin continued to have the pathogens at the end of the treatment period. Both patients had a neoplasm of the lung. All 11 patients who had soft tissue infections (nine of whom received cefmenoxime) responded well. Both antibiotics were well tolerated.

Neisseria flavescens is a rare cause of human disease. This is the first reported case of endocarditis caused by N. flavescens. The organism produced beta-lactamase, and penicillin therapy failed to cure the infection. Therapy with cefotaxime, to which the organism was highly sensitive, led to a complete and uneventful recovery.

Cefmenoxime administered intravenously was used to treat a variety of gynecologic and obstetric infections in 40 patients. Many were mixed infections. The mean age of the patients was 39.7 +/- 2.39 years. The dosage of cefmenoxime was 2 g per day (n = 30) or 1 g per day (n = 10). Cefmenoxime levels were assayed microbiologically in serum, milk, amniotic fluid, and placental tissues. The overall bacteriologic cure rate was 86 percent. Clinically, 100 percent of the patients were treated successfully. Side effects were generally mild, and in no case was treatment discontinued. Twelve hours after the last bolus injection, levels of cefmenoxime were 1.1 microgram/ml in serum and 1.75 microgram/ml in milk. Thirty minutes after a 1 g bolus injection in patients undergoing cesarean section, mean maternal serum concentrations were 33 micrograms/ml. Concentrations were 7.4 micrograms/ml in umbilical cord blood and 2.3 micrograms/ml in amniotic fluid.

The therapy of gram-negative bacillary meningitis is less than adequate to date; the agents recommended do not achieve bactericidal levels in purulent cerebrospinal fluid. Because optimal antibiotic therapy of meningitis occurs when the cerebrospinal fluid level of an antibiotic is above the concentration needed to kill the offending pathogen, another group of agents needs to be considered. The newer cephalosporins or cehalosporin-type antibiotics (cefotaxime, moxalactam), by virtue of their marked activity against gram-negative bacilli and their ability to achieve significant CSF levels, merit serious consideration as therapy for gram-negative bacillary meningitis. Investigators in Europe and the United States have developed preliminary data demonstrating the efficacy of these agents in a growing number of cases. In the group presented herein, of the 35 cases in which gram-negative bacillary meningitis was treated with the newer cephalosporins, there were only four failures.

Sixty patients (23 men and 37 women) with a median age of 56.7 years (range 20 to 80) and a median weight of 69 kg were treated with cefmenoxime as short-term perioperative prophylaxis. Patients were undergoing surgery for an infected gallbladder, bile duct, or colon or were being treated for local or diffuse peritonitis and soft tissue infections. Overall clinical efficacy including very good and good results could be achieved in 88.3 percent. Moderate clinical efficacy was achieved in six cases, two of which were due to Pseudomonas aeruginosa. In 38 of 60 patients an antibiogram could be performed before and after therapy. Of the isolated 46 strains, 40 pathogens (86.95 percent) were eradicated during cefmenoxime treatment and in two cases a replacement was observed. After one hour, peak concentrations in serum could be reached with over 70 micrograms/ml.

Information on 62 bacteriologically confirmed cases of bacterial meningitis treated with cefotaxime in this country was obtained retrospectively from infectious disease consultants. This series of cases differed markedly from the world cumulative case data thus far presented. One of the two most common organisms treated was the pneumococcus (allergy to penicillin or misdiagnosis of the Gram stain results were the major reasons given). The other organism was Klebsiella. Unanticipated bacteriologic successes were noted in two cases of staphylococcal meningitis secondary to parameningeal foci. The bacteriologic cure rate and survival rate were about 85 percent. Failure of monotherapy was seen in one case of Pseudomonas meningitis, as well as in three of five cases of Enterobacter meningitis. In addition, two cases of Escherichia coli meningitis in which moxalactam therapy inexplicably failed were cured with cefotaxime. Close analysis of killing kinetics appeared to explain the Enterobacter and E. coli failures. Thus, overall not all gram-negative species and not all isolates of any particular species that cause meningitis can be successfully treated by cephalosporins. Data obtained during the investigative trials do not appear to be entirely predicative of what occurred during the free clinical use of an antibiotic. Post-investigatory follow-up and surveillance of all newly introduced therapeutic agents are needed.

Ceftriaxone is a promising antimicrobial agent in the therapy of bacterial meningitis. The rationale for the clinical evaluation of ceftriaxone in patients with meningitis is based on the following favorable characteristics: ceftriaxone has excellent in vitro activity (MBC90 0.25 microgram/ml or less) against the major meningeal pathogens including meningococci, pneumococci, group B streptococci, Hemophilus influenzae, and Escherichia coli, but it is inactive against Listeria monocytogenes; ceftriaxone is rapidly bactericidal within purulent cerebrospinal fluid in experimental animal models of meningitis induced by pneumococci, group B streptococci, H. influenzae, and E. coli; against most of the major meningeal pathogens, the activity attained in cerebrospinal fluid in human subjects with bacterial meningitis is high (1:512 or greater) and active concentrations of ceftriaxone persist in cerebrospinal fluid for prolonged periods compared with those of other cephalosporins; the results of clinical trials reported to date in patients with meningitis are encouraging. Ceftriaxone deserves further clinical evaluation in the treatment of bacterial meningitis; the optimal dose, frequency of administration, and duration of therapy remain to be determined.

Cefmenoxime, a new semisynthetic third-generation cephalosporin, was evaluated in 105 patients (45 men and 60 women) with the following infections: skin or skin structure (33), pulmonary (22), urinary tract (30), and septicemia (20). Forty-two infections were hospital-acquired, 85 patients had underlying diseases, 29 patients required concomitant surgery, and 32 patients had positive results of blood culture. Cefmenoxime dosages ranged from 4 to 12 g per day intravenously for one and a half to 51 days. Cultures revealed 183 organisms in the 105 patients. Minimal inhibitory concentrations were obtained for cefmenoxime, cefoperazone, cefotaxime, cefamandole, cefoxitin, and moxalactam. Cefmenoxime and cefotaxime exhibited nearly equivalent activities against all organisms tested and were the most active agents tested against all aerobic and facultative organisms except Staphylococcus aureus. Mean serum peak and trough levels obtained after 2 g every six hours were 84.1 micrograms/ml (peak), 8.3 micrograms/ml (trough); and after 2 g every four hours, 106 micrograms/ml (peak) and 10.9 micrograms/ml (trough). Of 105 infections, 86 were clinically cured, three were not cured, and 16 were not evaluable. Safety studies revealed 24 transient reactions in 23 patients including eosinophilia, diarrhea, leukopenia, rash, elevated liver enzyme levels, Antabuse effect, and phlebitis. On the basis of these clinical and in vitro results, cefmenoxime is a safe drug for the treatment of infections caused by gram-negative and gram-positive aerobic organisms.

Cefmenoxime, a new parenteral beta-lactamase-resistant cephalosporin, was evaluated for safety and efficacy in 15 patients (10 male and five female) with acute (1 patient) and chronic (14 patients) osteomyelitis. Diagnosis was made by culture of the surgical biopsy specimen. Osteomyelitis was treated with 8 to 12 g of cefmenoxime per day (mean 9.1 g) for 42 to 66 days (mean 47.3). Staphylococcus aureus was the most frequently isolated organism. Minimum inhibitory concentrations (MICs) of cefmenoxime were determined and all pathogens were inhibited by 12.5 micrograms/ml or less, except for Enterobacter cloacae and Acinetobacter species, both of which had an MIC of 25.0 micrograms/ml. All patients had at least one surgical debridement. Of the 15 patients, 10 (67 percent) had the osteomyelitis "arrested." These patients have been followed up five to 14 months after completion of cefmenoxime therapy. Toxicity studies indicated mild elevations in serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase in two patients. Cefmenoxime appears to be a safe and effective antibiotic in the treatment of osteomyelitis.

Thirty pediatric and young adult patients with bacterial meningitis were treated with ceftriaxone or "standard therapy" in a comparative trial; 41 other patients with severe bacterial infections were treated with ceftriaxone in an open protocol. Meningitis and brain abscesses were treated successfully with 50 mg/kg of ceftriaxone every 12 hours. In children, other infections were treated with 25 to 37.5 mg/kg of ceftriaxone every 12 hours. Young adults with pneumonia received 1 g of the antibiotic every 12 hours, whereas those with soft tissue infections were treated every 24 hours. All patients responded to therapy, and in all but one was the infectious process sterilized. No significant toxicity was observed. Ceftriaxone appears to be an excellent single agent for the treatment of most severe bacterial infections in pediatric and young adult patients and need not be administered more frequently than once every 12 hours.

Oral ciprofloxacin (750 mg twice daily) was compared with intravenous cefotaxime (2 g three times daily) as therapy for 61 episodes of skin and skin structure infections occurring in adult patients. A variety of infections including cellulitis, infected ulcers, abscesses, and other miscellaneous infections were treated. Clinical cure was achieved in 77 percent (24 patients) of 31 patients treated with ciprofloxacin and in 76 percent (22 patients) of 28 patients treated with cefotaxime. The response was slower in infected diabetic patients than in non-diabetic patients in both groups. Side effects were minimal and appeared only in the cefotaxime group. Ciprofloxacin taken twice daily was as effective as cefotaxime administered intravenously three times daily in the treatment of skin and skin structure infections.

Mortality due to serious infections is significantly higher among elderly patients than among younger patients. This differential is particularly striking in some subsets of patients; for example, the mortality rate among older patients with afebrile bacteremia is 65 percent, compared with 25 to 35 percent in younger patients. Although serious underlying disease is an important reason for older patients' difficulties with infection, other problems of these patients include a tendency to deny the presence of disease and some obstacles to interaction with the health care system. Older patients with infection are less likely to present with typical symptoms, which makes early recognition difficult for physicians. For example, typical findings of sepsis (mental obtundation, tachycardia, and fever) may be absent in an elderly patient; the only clue may be the patient's failure to eat. Once sepsis is recognized, its source must be identified. Urinary tract infection is the most common cause of sepsis in the elderly and responds best to antibiotic therapy. Pneumonia is the next most common cause and leads to the highest mortality in this age group; rapid (sometimes invasive) methods must be utilized to identify the etiologic agent. In this life-threatening infection, initial antibiotic therapy should include an aminoglycoside, such as amikacin, to ensure the broadest coverage against the common pathogens. Supportive measures should be instituted for patients with sepsis, including careful monitoring of fluid intake and output and special attention to adequate oxygenation. Fluid volume replacement must be carried out in patients with septic shock, and hemodynamic monitoring with a Swan-Ganz catheter should be performed frequently. Careful consideration should be given to the use of corticosteroids and inotropic agents. After appropriate cultures have been obtained, antibiotics should be started; the time from initial presentation to the administration of the first dose of antibiotic should not exceed one hour. Important considerations in antibiotic selection include the patient's history and environment (community, nursing home, or hospital), anatomic location of the infection, and the pathogen. In our institution, initial empiric antibiotic therapy consists of a combination of amikacin and cefotaxime. When older patients are treated, adjustments in dosing should be based on estimates of kidney function.

In a single-blind, placebo-controlled randomized trial, 100 successive patients were enrolled with serious skin and soft-tissue infections, whose illnesses had precipitated an initial hospital admission or an extension of inpatient care. There were 93 evaluable patients who received either ofloxacin, 400 mg orally every 12 hours plus an intravenously administered placebo every eight hours, or cefotaxime, 2.0 g intravenously every eight hours plus an orally administered placebo every 12 hours. The average length of therapy was 12 days. Both patient groups had similar demographics and underlying conditions. Wound infection was the most common diagnosis, followed by abscess, cellulitis, and trophic ulcer. Multiple pathogens were commonly isolated from infected sites (1.4 pathogens/patient). The most common pathogen was Staphylococcus aureus, followed by Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Serratia marcescens, Proteus/Providencia spp., and Enterobacter spp. Persistence of the initial pathogen at the end of therapy was observed in 22.5 percent of the cefotaxime-treated group, but in only 10 percent of the ofloxacin-treated group. There was one clinical failure in the cefotaxime group, caused by a susceptible strain of Enterobacter cloacae, and there was one clinical failure in the ofloxacin group, in which the patient had an Acinetobacter calcoaceticus var. anitratus wound infection and subsequently developed a P. aeruginosa superinfection. Adverse experiences, including rash, insomnia, and nausea, occurred in 16 percent of the patients in each group. It was concluded that oral ofloxacin is as safe and efficacious as parenteral cefotaxime in the treatment of serious skin and skin structure infections.

Cefmenoxime was evaluated in an open trial consisting of 41 patients. Forty infections in 36 patients could be evaluated. Thirteen patients had pyelonephritis due to Escherichia coli (two bacteremic), Pseudomonas aeruginosa, Klebsiella pneumoniae, or Streptococcus faecalis; all improved and 12 of 13 were clinically cured, but one relapse (S. faecalis) occurred at two weeks. Six patients with cystitis due to E. coli, Citrobacter freundii, Serratia marcescens, P. aeruginosa, or S. faecalis all improved, but relapse or reinfection, or both, occurred in five due to P. aeruginosa, S. faecalis, C. fruendii, or E. coli. Neurogenic bladder or other complications were present in five of 13 patients with pyelonephritis and five of six with cystitis. Ten patients with pneumonia and one with tracheobronchitis due to Hemophilus influenzae, S. pneumoniae, S. agalactiae, or Neisseria meningitidis all improved and seven had resolution without relapse, but P. aeruginosa emerged in two patients, one of whom died. Eight soft tissue infections due to Staphylococcus aureus, Peptococcus prevotti, Streptococcus species, or infections of mixed origin resolved in six. Sterility of blood cultures was obtained in one patient with endocarditis due to S. anginosus, but other therapy was substituted. Clinical resolution of the toxic shock syndrome and subsequent negative endocervical cultures for S. aureus occurred in one. Granulocytopenia of unverified cause in four (with less than 1,500 mm3) and two (with less than 2,000 mm3) was reversible. Headache during treatment occurred in six patients and a possible disulfiram-like effect in three. Elevations of serum glutamic oxalacetic transaminase and alkaline phosphatase occurred in five, Coombs' positivity in two, and diarrhea in three. Clinical efficacy of cefmenoxime was significant. Possible side effects require further study.

A total of 560 patients were treated in two double-blind, randomized multicenter studies to compare the safety and efficacy of cefixime (400 mg administered once daily) and amoxicillin (250 or 500 mg administered three times daily) for the treatment of bacterial respiratory tract infections. Eighty percent of the 244 patients treated in the lower respiratory tract infections (LRTI) study had acute bronchitis. Streptococcus pneumoniae (13 percent), Haemophilus influenzae (28 percent), and Escherichia coli (10 percent) were the pathogens most frequently isolated from sputum in these patients. Among evaluable patients with positive bacterial culture results at baseline, a favorable clinical response (cured or improved) was obtained in 100 percent of the cefixime-treated patients (22 of 22) and in 96 percent of the amoxicillin-treated patients (23 of 24). Bacteriologic eradication rates were 100 percent and 83 percent for cefixime and amoxicillin, respectively. In the upper respiratory tract infections (URTI) study, 316 patients with pharyngitis (80 percent) or tonsillitis (14 percent) were treated. Group A, beta-hemolytic Streptococcus (69 percent) and H. influenzae (8 percent) were the pathogens most frequently isolated from the throat culture specimens of these patients. Favorable clinical results were obtained in 99 percent of the evaluable cefixime-treated group (n = 73) and in 98 percent of the amoxicillin-treated group (n = 66). The bacteriologic eradication rates were 93 percent and 100 percent, respectively. The adverse experiences reported during both studies were similar in nature and frequency to those reported for other beta-lactam antibiotics with the exception of a higher incidence of altered bowel movement (diarrhea and stool changes) with both drugs. These episodes usually resolved without remedial medication when the treatment was withdrawn. No significant adverse laboratory findings were observed. Results of these trials demonstrate that cefixime at a dosage of 400 mg once daily is an effective and safe oral antibiotic for the treatment of acute respiratory tract infections.

Single-dose ceftriaxone, 125 mg given intramuscularly, was compared with spectinomycin 2.0 g given intramuscularly in the treatment of women with uncomplicated gonorrhea. Cervical or anorectal gonococcal infection was eradicated in 54 (98 percent) of 55 women treated with ceftriaxone and 22 (96 percent) of 23 treated with spectinomycin. Cure rates for pharyngeal gonococcal infections were nine of 10 for ceftriaxone and four of eight for spectinomycin (p = 0.18). Neither agent eradicated concurrent Chlamydia trachomatis infection. The geometric mean minimal inhibitory concentration for ceftriaxone was 0.0038 microgram/ml for 65 pretreatment cervical isolates of beta-lactamase-negative Neisseria gonorrhoeae and all isolates were inhibited by 0.063 microgram/ml. Neither drug caused perceptible toxicity, but patient acceptance was better for ceftriaxone than for spectinomycin. A single 125 mg dose of ceftriaxone is an excellent regimen in the treatment of uncomplicated gonorrhea in women.

Monotherapy of osteomyelitis with the newer broad-spectrum beta-lactam antibiotics has become attractive because of the efficacy, safety, and cost of these antibiotics when compared with conventional combination therapy. Imipenem/cilastatin is a recent and promising addition to this antibiotic family. Experience with imipenem/cilastatin and that reported for cefotaxime, ceftazidime, and ceftizoxime in the treatment of biopsy-proved osteomyelitis was compared, using data from published reports from five centers. Two hundred forty-three patients were evaluable: 34 were treated with imipenem/cilastatin, 84 with cefotaxime, 122 with ceftazidime, and 33 with ceftizoxime. Staphylococcus aureus was isolated by 80 bone cultures and was the most common single species encountered. There were 75 isolates of Pseudomonas aeruginosa, 113 mixed Enterobacteriaceae species, 115 mixed gram-positive and -negative isolates of miscellaneous species, and 30 anerobic isolates. Polymicrobial infection was present in 101 cases (41.6 percent). Failure rates were similarly low in all groups (10 to 30 percent). However, resistance developed during therapy in all groups with P. aeruginosa. Side effects were predictably few, but reversible neutropenia, pseudomembranous colitis due to Clostridium difficile, and nausea required therapy to be discontinued in seven patients. Imipenem/cilastatin should prove to be a very effective and relatively safe single agent for treatment of osteomyelitis.