Post-antibiotic suppressive effect of ciprofloxacin against gram-positive and gram-negative bacteria.

The post-antibiotic suppressive effect (PAE) of different antibacterial agents against gram-positive bacteria has been known since the 1940s. Recently, it has been demonstrated that quinolone antimicrobial agents exert a PAE against gram-negative bacteria. In this study, the PAEs of ciprofloxacin against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Serratia marcescens, Staphylococcus aureus, and Streptococcus faecalis were determined. The differences in PAE determined by three different techniques--filtration, centrifugation, and dilution--were assessed for S. aureus and E. coli. Ciprofloxacin had a PAE by all three methods, and filtration was used in the majority of studies. A ciprofloxacin concentration of 3 micrograms/ml in Mueller-Hinton broth, pH 7.4, with two hours of exposure produced a PAE of three to four hours for gram-negative bacilli, and 1.9 hours for S. aureus, but had no effect on S. faecalis. Exposure of organisms in urine to 300 micrograms/ml of ciprofloxacin for two hours produced a two- to six-hour PAE for E. coli, S. marcescens, P. aeruginosa, and K. pneumoniae. Use of Mueller-Hinton broth with a magnesium concentration of 8 mM, pH 5.5, yielded similar results. Using human serum, a four-hour PAE was found for P. aeruginosa. There was a progressive increase in the PAE as the duration of ciprofloxacin exposure was increased from 0.9 hours to three hours. Increasing the ciprofloxacin concentration from two to eight times the minimal bactericidal concentration (MBC) for P. aeruginosa or from four to 16 times the MBC for E. coli did not cause a significant difference in the PAE using a two-hour exposure. Overall, ciprofloxacin produced an excellent PAE for most gram-negative bacteria and for S. aureus, but not for S. faecalis. A PAE caused by ciprofloxacin can be demonstrated in broth supplemented with magnesium, in urine, in serum, and in broth with the pH adjusted to an acidic level and with the increased magnesium concentration found in urine. These results support less frequent dosing programs for ciprofloxacin in the treatment of tissue and urinary infections.

In vitro activity of fleroxacin in combination with other antimicrobial agents.

The trifluoroquinolone fleroxacin inhibits the majority of Enterobacteriaceae at concentrations < or = 1 micrograms/mL and most Pseudomonas aeruginosa and staphylococci at < or = 2 micrograms/mL. The purpose of this study was to determine the effect of the combination of fleroxacin with other antimicrobial agents. Previous studies that used checkerboard assay, fixed concentrations, and killing curves were reviewed, and these methods were used to evaluate the combination of fleroxacin and agents that had not been previously studied. The combination of fleroxacin with such aminoglycosides as gentamicin, amikacin, and tobramycin is indifferent against most Enterobacteriaceae, as is the combination of fleroxacin with penicillins, cephalosporins, rifampin, clindamycin, and metronidazole. Combinations of fleroxacin with penicillins, cephalosporins, imipenem, aminoglycosides, clindamycin, metronidazole, and rifampin are indifferent against P. aeruginosa. Fosfomycin and fleroxacin acted synergistically against P. aeruginosa. Against staphylococci, combinations of fleroxacin with oxacillin, rifampin, or fosfomycin had synergistic or additive effects, whereas combinations of fleroxacin with vancomycin, gentamicin, or metronidazole have shown indifference. No synergy or antagonism has been found for combinations of fleroxacin with penicillin, vancomycin, erythromycin, clindamycin, or rifampin against streptococci or enterococci. The combination of fleroxacin and metronidazole has proved synergistic against various Bacteroides species. In general, combinations of fleroxacin with other antimicrobial agents display indifference and rarely synergy. Thus, fleroxacin can be combined with other antibiotics to enlarge the spectrum of activity.

Resistance to ciprofloxacin appearing during therapy.

The development of resistance to ciprofloxacin in nine clinical isolates of Pseudomonas aeruginosa was investigated. Isolates had increases in minimal inhibitory concentrations (MICs) from 0.25 to 16 micrograms/ml. The isolates also became resistant to ofloxacin and norfloxacin, but did not show increases in MICs to aminoglycosides, antipseudomonas penicillins, or cephalosporins. One isolate from a patient with endocarditis showed a reduction in a 43-kD outer membrane protein and simultaneous increase in the imipenem MIC. This isolate also showed impaired uptake of ciprofloxacin. Respiratory isolates from cystic fibrosis patients did not show loss of outer membrane protein. MICs were lowered by ethylene diaminetetra-acetic acid, suggesting changes in lipopolysaccharide. Resistant isolates were synergistically inhibited by combinations of ciprofloxacin plus tobramycin or ceftazidime, but MICs remained beyond the achievable serum level.

Pharmacology of ticarcillin combined with clavulanic acid in humans.

Serum and urine levels of ticarcillin and clavulanic acid after administration of doses of 50 mg/kg and 1.7 mg/kg or 50 mg/kg and 3 g/0.1 g, respectively, are potentially toxic to susceptible bacteria. Both compounds are widely distributed in body tissues and fluids, with concentrations exceeding the minimal inhibitory concentrations of most pathogens. Excretion is primarily renal, although there is some metabolism of clavulanate in the body. Due to accumulation, dosage adjustment is required for patients with renal insufficiency. Both ticarcillin and clavulanic acid are cleared by hemodialysis.

Effect of ciprofloxacin on fecal flora of patients with cystic fibrosis and other patients treated with oral ciprofloxacin.

Ciprofloxacin is a fluorinated carboxyquinolone that inhibits Enterobacteriaceae, staphylococci, and Pseudomonas at low concentrations. It has poor activity against Bacteroides fragilis. In this study, the effect of administration of ciprofloxacin on bowel flora was determined in patients treated for different infections. Patients, aged 22 to 70 years, were treated with 500 mg of ciprofloxacin every 12 hours or 750 mg every eight hours for seven to 42 days. Some patients had advanced cystic fibrosis; other patients had infections with resistant bacteria. Infecting organisms were Pseudomonas aeruginosa, Staphylococcus aureus, Serratia, and Acinetobacter. Sites of infections were lung, soft tissue, and urinary tract. Stool samples were evaluated initially, during therapy, and after therapy. No resistant gram-negative aerobic species emerged; five patients had yeast colonization, staphylococci were found in three patients, and streptococci were found in one patient. Ciprofloxacin did not select resistant gram-negative bacteria in the stool, although sputum isolates showed increases in minimal inhibitory concentrations. Resistant bacteria were not selected in the fecal flora of patients who had received beta-lactam and aminoglycoside antibiotics before therapy with ciprofloxacin.

Postantibiotic effect of ceftibuten on respiratory pathogens.

The postantibiotic effect (PAE) of ceftibuten, a novel beta-lactamase-stable cephem, was determined for Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. The ceftibuten PAE after a 2-hour exposure to 2 micrograms/ml (4 x minimum inhibitory concentration) for S. pyogenes was 2.7 to > 10 hours. The PAE for S. pneumoniae after a 2-hour exposure to 15 micrograms/ml, concentrations that are achieved in man after usual therapeutic doses, was 1.1 to 3.4 hours and the PAE for H. influenzae was 1 to 1.1 hours. M. catarrhalis had a PAE of 1.5 to 1.8 hours after exposure to 15 micrograms/ml of ceftibuten. The ceftibuten PAE was not affected by serum. The ceftibuten PAE was prolonged by exposure to a sub-minimum inhibitory concentration concentration of ceftibuten as would occur in the clinical situation. The PAE of ceftibuten was not affected by the copresence of erythromycin as would occur when treating infections in which atypical organisms are suspected. There was no correlation between bacterial reduction in colony-forming units and the duration of PAE. A level of 6 micrograms/ml of ceftibuten had a similar bacterial killing activity compared with a 6-hour exposure to 15 micrograms/ml of ceftibuten against S. pneumoniae, H. influenzae and M. catarrhalis. This study suggests that ceftibuten can be administered orally, once daily in an adult dose of 400 mg or a pediatric dose of 9 mg/kg, to treat respiratory infections caused by the most common pathogens.

Nonsusceptible Streptococcus pneumoniae in children with chronic otitis media with effusion and recurrent otitis media undergoing ventilating tube placement.

CONTEXT: Children with chronic otitis media are at risk for nonsusceptible Streptococcus pneumoniae (NSP) infection. If these children undergo ventilating tube placement, there is an opportunity to culture middle ear fluid and the nasopharynx to determine carriage of NSP. OBJECTIVE: To determine the incidence of NSP carriage, NSP antibiotic susceptibility and risk factors for NSP carriage in children with chronic otitis media undergoing tube placement. DESIGN AND SETTING: Prospective cohort study in an academic medical center with recruitment of patients from an otolaryngology private practice and clinic. PATIENTS: Children < 18 years of age undergoing tube placement for chronic otitis media. INTERVENTIONS: Myringotomy and tube placement, with culture of middle ear fluid and nasopharynx. MAIN OUTCOME MEASURES: The incidence of NSP cultured from the middle ears and nasopharynx of recruited subjects with the use of the minimum inhibitory concentration break points for penicillin susceptibility recommended by the National Committee for Clinical Laboratory Standards. RESULTS: S. pneumoniae was identified in at least 1 site from 23 of 300 study subjects (7.6%); of these 23, 12 case subjects (52.2%) harbored NSP. Of the risk factors assessed by preoperative questionnaire, only younger age was associated with NSP colonization (P < 0.0001). Of the six oral cephalosporins studied, cefpodoxime and cefuroxime showed good in vitro activity against S. pneumoniae isolates with intermediate penicillin resistance. CONCLUSIONS: Children with chronic otitis media undergoing tube placement may carry NSP and provide a means of monitoring the incidence of NSP and antibiotic susceptibilities for children with ear infections in their communities. Younger age is a risk factor for NSP carriage in this population.

In vitro activity of LY264826 compared to other glycopeptides and daptomycin.

LY264826 a new naturally occurring glycopeptide inhibited 90% of methicillin-susceptible and -resistant Staphylococcus aureus at 1 micrograms/ml. LY264826 had similar activity against methicillin-susceptible and -resistant coagulase-negative staphylococci. The LY264826 MIC90 for Streptococcus pyogenes was 0.25 microgram/ml, twofold more active than vancomycin and twofold less active than teicoplanin. LY264826 was eightfold more active than vancomycin and twofold more active than teicoplanin against enterococci. LY264826 inhibited Streptococcus pneumoniae at 0.25 microgram/ml and Listeria monocytogenes at 0.5 microgram/ml. Clostridium were inhibited by less than or equal to 0.25 microgram/ml of LY264826 and peptococci, peptostreptococci, and Fusobacterium were inhibited by less than 0.5 microgram/ml. Bacteroides species were LY284826 -resistant as were all Enterobacteriaceae, Flavobacterium, and Neisseria spp. Minimum bactericidal and inhibitory concentrations (MBCs and MICs) were within a dilution for S. aureus, S. pyogenes, and S. pneumoniae, but greater than or equal to 32-fold greater for enterococci.

The in vitro activity and beta-lactamase stability of cefpiramide compared with other beta-lactam antibiotics.

The in vitro activity of cefpiramide, a new ureido cephalosporin antibiotic, was determined against 1128 gram-positive and gram-negative aerobic and anaerobic bacteria selected for resistance to ampicillin and cefazolin. Cefpiramide was less active on a milligram basis than cefotaxime, ceftazidime, moxalactam, and aztreonam against all of the members of the Enterobacteriaceae. Cefpiramide inhibited many Pseudomonas aeruginosa resistant to carbenicillin, piperacillin, and cefotaxime, but it was less active than ceftazidime and cefsulodin. Cefpiramide inhibited staphylococci and streptococci and had appreciable activity against Streptococcus faecalis and Listeria moncytogenes. It had less activity than cefoxitin against anaerobic species. Cefpiramide inhibited permeability mutants of Escherichia coli at lower concentrations than the parent strain, suggesting an effect of entry upon its activity. Although cefpiramide was resistant to attack by most chromosomal beta-lactamases, it was hydrolyzed by the common plasmid beta-lactamases TEM and SHV and by the chromosomal Proteus vulgaris, type Ic, cephalosporinase.

Synergy of new C-3 substituted cephalosporins and tobramycin against Pseudomonas aeruginosa and Pseudomonas cepacia.

The effects of the combination of E-1040, a new cephalosporin, ceftazidime, cefpirome, or cefepime with tobramycin against 40 Pseudomonas aeruginosa and 16 P. cepacia isolates from cystic fibrosis patients were examined. Synergy fractional inhibitory concentration less than or equal to 0.5 was found against P. aeruginosa when tobramycin was combined with E-1040 32%, cefpirome 32%, cefepime 22%, and ceftazidime 22%. Fifty-two percent of isolates showed an additive response for E-1040, 60% for cefpirome, 45% cefepime, and 55% ceftazidime, p greater than 0.05. The differences were not statistically significant. Synergy was not more likely to be achieved if the isolates were susceptible or resistant to either the aminoglycoside or cephalosporin. None of the E-1040-resistant isolates, all of which were tobramycin-resistant, became susceptible when tested with an aminoglycoside, whereas 15 of 34 cefpirome-resistant, 13 of 30 cefepime-resistant, and seven of 14 ceftazidime-resistant isolates became susceptible. Synergy of aminoglycoside and the cephalosporins against P. cepacia was found for 25% with E-1040, 44% with cefpirome, 38% with cefepime, and 31% with ceftazidime. These differences were not statistically significant.

Cefotaxime and desacetylcefotaxime: an example of advantageous antimicrobial metabolism.

Although the antibacterial activity of desacetylcefotaxime (des-CTX), the principal metabolite of cefotaxime (CTX), is eightfold lower than cefotaxime, the metabolite inhibits many B-lactamase-producing Enterobacteriaceae and unusual Pseudomonas species resistant to agents such as cefamandole, cefoxitin, and cefoperazone. des-CTX is more stable than CTX to attack by beta-lactamases of some species such as Bacteroides fragilis, Proteus vulgaris, and the k-1 enzyme of Enterobacter-Klebsiella. des-CTX acts synergistically with CTX against many Enterobacteriaceae and Streptococcus faecalis. The antibacterial activity of the combination of CTX/des-CTX indicates that the drug can be administered every 8-12 hr and provides excellent, broad-spectrum antimicrobial activity.

Antimicrobial activity and beta-lactamase stability of SK&F 88070 compared with other agents.

The in vitro activity and beta-lactamase stability of SK&F 88070 (7-[[2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-3-[[ [1-(2-sulfaminoethyl)-1H-tetrazol-5-yl]thio]methyl]-3- cephem-4-carboxylic acid) a new parenteral cephalosporin was investigated against 780 types of bacteria. SK&F 88070 inhibited 90% of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella species, Shigella species, Morganella morganii, and Citrobacter diversus at less than or equal to 0.5 micrograms/ml. Its activity against these species was similar to cefotaxime and moxalactam and superior to cefoperazone and piperacillin. It was less active than cefoperazone against Pseudomonas aeruginosa and less active than cefotaxime or cefoperazone against Staphylococcus aureus. SK&F 88070 inhibited hemolytic streptococci and Streptococcus pneumoniae at less than or equal to 0.12 micrograms/ml. Enterobacter species, Citrobacter freundii, and Serratia, which were resistant to cefotaxime and moxalactam were resistant to SK&F 88070. It was not hydrolyzed by plasmid beta-lactamases, but was hydrolyzed by the Proteus vulgaris type 1c enzyme. SK&F 88070 inhibited Richmond-Sykes type 1a beta-lactamases.

Resistance of Xanthomonas maltophilia to antibiotics and the effect of beta-lactamase inhibitors.

We examined the susceptibility of 50 isolates of Xanthomonas maltophilia and the effect of beta-lactamase inhibitors upon the susceptibility. The majority of isolates were resistant to azlocillin, piperacillin, mezlocillin, ticarcillin, cefotaxime, ceftizoxime, ceftriaxone, cefoperazone, and ceftazidime. All isolates were resistant to imipenem, CGP 31608, aztreonam, and carumonam. Although disk susceptibility tests showed that the combination of clavulanate with ticarcillin inhibited many isolates, at a ratio of 1:20 few isolates were susceptible to the combination. Addition of clavulanate to aztreonam and to imipenem failed to make organisms susceptible. Sulbactam combined with cefoperazone made some organisms susceptible, but ampicillin-sulbactam was ineffective, whereas tazobactam combined with piperacillin at a ratio of 1:4 made half the isolates have MICs of 32 micrograms/ml or less. The beta-lactamases from the isolates hydrolyzed all of the beta-lactams.

In vitro activity of a new cephalosporin ME-1206 compared with other agents.

The in vitro activity of ME-1206, a new aminothiazolyl cephalosporin that can be orally absorbed when converted to an ester, was compared with that of other beta-lactams. ME-1206 inhibited 50% of the Enterobacteriaceae at 2 micrograms/ml, similar to cefotaxime, ceftazidime, and cefixime. It did not inhibit, MIC greater than or equal to 32 micrograms/ml, Enterobacter species or Citrobacter freundii resistant to cefotaxime and ceftazidime, and it was less active than cefotaxime and ceftazidime against Serratia marcescens. Haemophilus influenzae, Neisseria gonorrhoeae, and Moraxella catarrhalis were inhibited by less than or equal to 0.25 micrograms/ml of ME-1206 inhibited hemolytic streptococci groups A, B, C, and G, MIC90 0.06 micrograms/ml, but it did not inhibit enterococci. Pseudomonas aeruginosa and other pseudomonads were resistant to ME-1206. MICs and MBCs of ME-1206 for susceptible species were within a dilution. ME-1206 was not hydrolyzed by TEM-1 or TEM-2, but was hydrolyzed by TEM-3 and TEM-5. ME-1206 was hydrolyzed by beta-lactamases of Morganella, Proteus vulgaris, and K1 of Klebsiella oxytoca, but minimally by the P99 beta-lactamase of Enterobacter cloacae. ME-1206 is comparable in in vitro activity and beta-lactamase stability to many of the current cephalosporins.

Activity of cephalosporins against coagulase-negative staphylococci.

Staphylococcus epidermidis has become an increasingly important pathogen as the cause of serious postoperative infection after heart and orthopedic surgery. We studied the susceptibilities of 80 blood, sternotomy, and hip isolates to vancomycin, cefazolin, cefuroxime, oxacillin, erythromycin, ciprofloxacin, and ofloxacin. The MIC90 of methicillin-susceptible isolates was 4 micrograms/ml for cefazolin and cefamandole, 8 micrograms/ml for cefuroxime, and 4 micrograms/ml for vancomycin. At 48 hr the MIC90 rose to 32 micrograms/ml for cefazolin and greater than 128 micrograms/ml for cefuroxime, and remained at 4 micrograms/ml for cefamandole and vancomycin. The MIC90 of methicillin-resistant isolates at 48 hr was 16 micrograms/ml cefamandole, 64 micrograms/ml cefazolin, greater than 128 micrograms/ml cefuroxime, and 4 micrograms/ml vancomycin. Ciprofloxacin and ofloxacin inhibited the majority of isolates at 1 microgram/ml, and vancomycin at 4 micrograms/ml. The new peptolide, daptomycin, also inhibited S. epidermidis at less than or equal to 1 microgram/ml.

In vitro activity of cefquinome, a new cephalosporin, compared with other cephalosporin antibiotics.

The in vitro activity of cefquinome, a new aminothiazolyl cephalosporin with a C-3 bicyclic pyridinium group, was compared with ceftazidime, cefpirome, and cefepime. Cefquinome inhibited members of the Enterobacteriaceae at less than or equal to 0.5 microgram/ml for Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Citrobacter diversus, Salmonella Shigella, Proteus mirabilis, Morganella, and Providencia. Although most Citrobacter freundii and Enterobacter cloacae were inhibited by less than 2 micrograms/ml, some strains resistant to ceftazidime were resistant, [minimum inhibitory concentration (MIC) greater than 16 micrograms/ml]. Serratia marcescens were inhibited by less than 1 microgram/ml and Pseudomonas aeruginosa by 8 micrograms/ml similar to the activity of cefepime. The majority of Haemophilus influenzae and Neisseria gonorrhoeae were inhibited by less than 0.25 microgram/ml. Most enterococci had cefquinome MICs of 4-8 micrograms/ml. Cefquinome was extremely active against group-A streptococci and Streptococcus pneumoniae with MICs less than 0.12 microgram/ml. 90% of methicillin-susceptible Staphylococcus aureus 90% were inhibited by 2 micrograms/ml. Overall, the in vitro activity of cefquinome was comparable with aminothiazolyl cephalosporins. It inhibited some Enterobacter and Citrobacter freundii resistant to ceftazidime as did cefpirome and cefepime. Cefquinome was not destroyed by the common plasmid beta-lactamases TEM-1, TEM-2, SHV-1, or by the chromosomal beta-lactamases of Klebsiella, Branhamella, and Pseudomonas, but it was hydrolyzed by TEM-3, TEM-5, and TEM-9. Its activity was not adversely decreased in different medium or protein, and minimum bactericidal concentrations (MBCs) for most species except for Enterobacter were within a dilution of MICs.

In vitro activity of CP-74,667. A new fluoroquinolone compared with other quinolones.

CP-74,667, a 6-fluoro-7-bridged piperazinyl-1-cyclopropyl-4 quinolone, inhibited 90% of staphylococci, beta-hemolytic streptococci, enterococci, Enterobacteriaceae, and Pseudomonas aeruginosa at less than or equal to 2 micrograms/ml. Ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus had minimum inhibitory concentration (MIC50) of 4 micrograms/ml and an MIC90 of 8 micrograms/ml. CP-74,667 was fourfold more active than ciprofloxacin against Streptococcus pneumoniae and St. pyogenes, but equal or less active than tosufloxacin against Gram-positive species. The MIC90 for P. aeruginosa was 5 micrograms/ml similar to temafloxacin. The CP-74,667 MIC90 for Bacteroides fragilis was 2 micrograms/ml, equal to tosufloxacin and temafloxacin. Activity was eight- to 16-fold less at pH 5.5 compared with pH 7.4 and also eight- to 16-fold less in urine. Magnesium ions markedly increased the CP-74,667 minimum bactericidal concentrations (MBCs). The development of resistance to CP-74,667 was similar to that found for other fluoroquinolones.

In vitro activity of an oxycephem OCP 9-176 compared with its sulfur analog and other beta-lactams.

OCP 9-176 is an oxycephem antibiotic that contains a 2-aminothiazolyl, carboxypropyl side chain at C-7 and a pyridinium thiomethyl group at C-3. OCP 9-176 was generally twofold less active than its sulfur-containing analog ME 1228 against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Providencia stuartii, Proteus vulgaris, and Serratia marcescens. Activity against Enterobacter cloacae and Citrobacter freundii was equivalent. OCP 9-176 was twofold less active than ME-1228 against Pseudomonas aeruginosa and Acinetobacter species. Activity of the two agents was similar against Staphylococcus aureus and Staphylococcus epidermidis. Although OCP 9-176 inhibited E. coli containing TEM-1 and TEM-2, it was less active than ME-1228. Klebsiella organisms with SHV-1 and K-2 beta-lactamases were inhibited, but TEM-3-containing isolates had MICs of 16 micrograms/ml. OCP 9-176 was minimally hydrolyzed by TEM-1, PSE-1, K-1, and P99, and it was a poor inhibitor of P99. Replacement of sulfur with oxygen does not increase the activity of compounds with sulfopyridinium methyl groups at C-3.

Antibacterial activity of rokitamycin compared with that of other macrolides.

The activity of rokitamycin, a 16-membered macrolide, was compared with other macrolides and agents used to treat respiratory infections. Rokitamycin had in vitro activity against streptococci and Streptococcus pneumoniae comparable to the other macrolides, inhibiting most organisms at less than 0.03 to 0.5 microgram/ml. It was the most active macrolide agent against Staphylococcus aureus, inhibiting 90% at 1 microgram/ml. Macrolide-resistant streptococci and staphylococci in which resistance was inducible were inhibited, but constitutively resistant Gram-positive bacteria were resistant. Rokitamycin was less active than erythromycin against Haemophilus influenzae, but had activity comparable to erythromycin against Moraxella catarrhalis and Neisseria gonorrhoeae. It inhibited Clostridium spp. and peptostreptococci, but had poor activity against Bacteroides species. Rokitamycin was bactericidal for streptococci and staphylococci, but not for enterococci. Overall rokitamycin has in vitro activity comparable to currently available 14-membered macrolides. Its clinical utility will be influenced by the degree of metabolism to less active metabolites since 70% is rapidly metabolized.

Antimicrobial effects of the combination of ceftibuten and an orally absorbed penem SCH 29482.

Ceftibuten is a new beta-lactamase-stable 3-aminothiazolyl cephalosporin that lacks activity against staphylococci and group-B streptococci. We determined the effect of the combination of ceftibuten with SCH 29482, an orally absorbed penem. The combination of the two agents was additive for 25% or indifferent for 57% of the Gram-positive species, Haemophilus, and Moraxella tested with a mean fractional inhibitory concentration (FIC) index of 0.75. The combination of ceftibuten and SCH 29482 was also indifferent for Bacteroides fragilis and other Bacteroides species, all of which were inhibited by less than or equal to micrograms/ml of SCH 29482. Antagonism of the combination was found for 80% of Serratia marcescens and for 30% of Citrobacter freundii and Enterobacter cloacae. Overall, the combination of ceftibuten and SCH 29482 at concentrations that can be achieved in serum after ingestion of 400 and 50 micrograms/ml, respectively, provided antibacterial activity against most Gram-positive aerobic and anaerobic species that cause upper respiratory, intraabdominal, and urinary infections.