Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sulbactam (SB) and clavulanic acid (CA) are irreversible inhibitors of the beta-lactamases in the Richmond and Sykes classes II-VI. When combined with ampicillin and ticarcillin, SB and CA, respectively, extend the spectrum of activity of these penicillins to include some beta-lactamase-producing aerobes (Enterobacteriaceae, Hemophilus influenzae, staphylococci) and anaerobes (Bacteroides fragilis group) which would otherwise be resistant. Neither effectively inhibits the class I beta-lactamases frequently produced by Pseudomonas aeruginosa, Enterobacter, and Serratia, in part explaining the resistance observed with these organisms. Clinically, both agents were as effective as the comparative therapies in all but two of the trials reviewed. Given the current data, the decision to add these agents to the formulary should be based on hospital resistance patterns and on the cost of these antimicrobials in comparison to conventional therapies.
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PMID:Ampicillin-sulbactam and ticarcillin-clavulanic acid: a comparison of their in vitro activity and review of their clinical efficacy. 174 24

beta-Lactamases have been known since the early 1940s when they were recognized as a major mechanism of resistance in Staphylococcus aureus. The synthesis of semisynthetic penicillins provided agents that overcame the resistance of staphylococci, but as gram-negative bacteria became increasingly important as the cause of infections, plasmid-mediated beta-lactamases were recognized in the Enterobacteriaceae, Haemophilus, and chromosomally mediated beta-lactamases in Klebsiella, and Bacteroides were found to be the mechanism of resistance of these species to ampicillin and related penicillins. Two approaches to the problem have been developed. One is to make stable compounds. This has been possible in the cephalosporin family. The other method has been to find inhibitors of beta-lactamases. Clavulanate is a beta-lactamase inhibitor that, in combination with amoxicillin, allows the combination to inhibit many of the organisms that are resistant to amoxicillin. Similarly, clavulanate has been combined with ticarcillin to provide a parenteral agent to inhibit beta-lactamase-producing bacteria and retain activity against Pseudomonas. Sulbactam has been combined with ampicillin. The combination of suicide inhibitors with other beta-lactams has provided agents that inhibit many of the bacteria present in mixed cutaneous infections. Clinical studies have established the efficacy of the clavulanate-amoxicillin and clavulanate-ticarcillin combinations in skin and skin-structure infections. These agents offer an alternative to other drugs when treating cutaneous infections.
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PMID:Beta-lactamases, beta-lactamase inhibitors, and skin and skin-structure infections. 218 13

Sulbactam/Ampicillin (SBT/ABPC), a combination at a fixed ratio of ABPC and SBT which is an irreversible inhibitor of beta-lactamase in a 2:1 ratio, was clinically evaluated for its efficacy and safety in 24 patients with ages from 5 month-old to 12 years old with bacterial infection. The results obtained are summarized as follows. 1. A pharmacokinetic study following 30 mg/kg SBT/ABPC administration by 30 minutes drip infusion or intravenous bolus injection showed that mean half-lives of SBT and ABPC were 48.9 minutes and 40.2 minutes, respectively, and mean urinary excretion rates of SBT and ABPC in the first 6 hours were 67.1% and 48.3%, respectively. 2. SBT/ABPC was administered to 14 patients with bronchopneumonia, 4 patients with tonsillitis, a patient each with acute upper respiratory infection, with submandibular lymphadenitis, with phlegmon, with enterocolitis, with pyelonephritis and with cystitis at a daily dosage of 88.2-133.3 mg/kg, divided into 3 or 4, by intravenous bolus injection or by 30 minutes drip infusion. Clinical responses of the 24 patients were as follows: excellent: 17 patients, good: 7 patients. The efficacy rate was 100%. 3. Neither clinical adverse reactions nor abnormal laboratory test values, except slight eosinophilia in a patient and an elevation of GOT, GPT in another were observed. 4. MICs of SBT/ABPC against 7 strong beta-lactamase producing strains isolated from some of the patients were as follows. MIC against a strain of Staphylococcus aureus was 3.13 micrograms/ml, MICs against 2 out of 5 strains of Branhamella catarrhalis were 0.10 microgram/ml and those of the remaining 3 strains were 0.20 microgram/ml. MIC against a strain of Haemophilus parainfluenzae was 3.13 micrograms/ml. 5. These data described above show that SBT/ABPC has excellent bactericidal capacity against beta-lactamase producing bacteria as well as beta-lactamase non-producing Gram-positive and negative bacteria and suggest that SBT/ABPC is a very useful antibiotic for pediatric patients.
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PMID:[Clinical evaluation of sulbactam/ampicillin in children]. 266 51

A total of 82 patients involving 83 episodes of proven or presumed bacterial infection were treated with sulbactam/ampicillin. These included 36 cases of soft tissue infection or abscess, four cases of joint or bone infection, 20 cases of respiratory tract infection (17 cases of pneumonia, two of otitis media, and one of tonsillitis), 15 urinary tract infections, three cases of enterocolitis, one case of infective endocarditis, two cases of septicemia, and two of peritonitis. The causative pathogen was isolated in 48 cases (49 infections). These pathogens included Staphylococcus aureus 13 cases, Staphylococcus epidermidis one, Streptococcus pyogenes two, Streptococcus pneumoniae two, Viridans group streptococcus two, peptostreptococcus one, Haemophilus influenzae one, Escherichia coli 12, Enterobacter cloacae three, Proteus mirabilis one, Acinetobacter calcoaceticus one, Salmonella spp. two, Shigella sonnei one, Bacteroides fragilis one, and polymicrobial infections of various combinations in five cases. No bacterial pathogens were isolated in 34 infections, 14 cases of pneumonia and 15 soft tissue infections. Sulbactam/ampicillin was given by intravenous bolus in a dosage range of 75-450 mg/kg/day in four divided doses for variable periods of time depending on the type and severity of the infection. Of a total of 83 episodes of infections, 80 (96.4%) cases were either cured or improved. Bacteriologic eradication also occurred in 46 (93.9%) of 49 infections. Side effects were diarrhea in two patients, acute hemolytic anemia in one patient, and transient elevations in SGOT and leukopenia in one patient. Side effects disappeared upon completion of treatment. Sulbactam/ampicillin is a safe and effective antibiotic for the treatment of common pediatric infections.
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PMID:Intravenous sulbactam/ampicillin in the treatment of pediatric infections. 268 18

Eighty-one patients ages one month to 14 years with meningitis were randomized to receive either sulbactam (50 mg/kg per day) and ampicillin (400 mg/kg per day; 41 patients) or chloramphenicol and ampicillin (40 patients). The groups were comparable in terms of sex and degree of illness; however, more patients treated with chloramphenicol/ampicillin than patients treated with sulbactam/ampicillin were younger than 12 months of age (78% vs. 56%). Pathogens were isolated from the cerebrospinal fluid (CSF) of 65 (80%) of the 81 patients. In the sulbactam/ampicillin group, there were 18 Haemophilus influenzae isolates (one resistant to ampicillin), five Streptococcus pneumoniae, five Neisseria meningitidis, one Klebsiella pneumoniae, one Pseudomonas aeruginosa, and one Listeria. In the chloramphenicol/ampicillin group, there were 19 H. influenzae isolates, 10 S. pneumoniae, three N. meningitidis, one Haemophilus parainfluenzae, and one Citrobacter. Of 63 patients with assessable CSF pathogens, one (3%) of 29 treated with sulbactam/ampicillin died (S. pneumoniae) and six (18%) of 34 treated with chloramphenicol/ampicillin died (two, H. influenzae; three, S. pneumoniae; and one, Citrobacter). Twelve percent in the sulbactam/ampicillin group and 18% in the chloramphenicol/ampicillin group had neurologic sequelae. No clinically significant reactions or toxicities were noted. Sulbactam/ampicillin was as effective as chloramphenicol/ampicillin in the treatment of meningitis.
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PMID:Sulbactam/ampicillin vs. chloramphenicol/ampicillin for the treatment of meningitis in infants and children. 302 15

beta-Lactamases constitute the major defense mechanism of pathogenic bacteria against beta-lactam antibiotics. When the beta-lactam ring of this antibiotic class is hydrolyzed, antimicrobial activity is destroyed. Although beta-lactamases have been identified with clinical failures for over 40 years, enzymes with various abilities to hydrolyze specific penicillins or cephalosporins are appearing more frequently in clinical isolates. One approach to counteracting this resistance mechanism has been through the development of beta-lactamase inactivators. beta-Lactamase inhibitors include clavulanic acid and sulbactam, molecules with minimal antibiotic activity. However, when combined with safe and efficacious penicillins or cephalosporins, these inhibitors can serve to protect the familiar beta-lactam antibiotics from hydrolysis by penicillinases or broad-spectrum beta-lactamases. Both of these molecules eventually inactivate the target enzymes permanently. Although clavulanic acid exhibits more potent inhibitory activity than sulbactam, especially against the TEM-type broad-spectrum beta-lactamases, the spectrum of inhibitory activities are very similar. Neither of these inhibitors acts as a good inhibitor of the cephalosporinases. Clavulanic acid has been most frequently combined with amoxicillin in the orally active Augmentin and with ticarcillin in the parenteral beta-lactam combination Timentin. Sulbactam has been used primarily to protect ampicillin from enzymatic hydrolysis. Sulbactam has been used either in the orally absorbed prodrug form as sultamicillin or as the injectable combination ampicillin-sulbactam. Synergy has been demonstrated for these combinations for most members of the Enterobacteriaceae, although those organisms that produce cephalosporinases are not well inhibited. Synergy has also been observed for Neisseria gonorrhoeae, Haemophilus influenzae, penicillinase-producing Staphylococcus aureus, and anaerobic organisms. These antibiotic combinations have been used clinically to treat urinary tract infections, bone and soft-tissue infections, gonorrhea, respiratory infections, and otitis media. Gastrointestinal side effects have been reported for Augmentin and sultamicillin; most side effects with these agents have been mild. Although combination therapy with beta-lactamase inactivators has been used successfully, the problem of resistance development to two agents must be considered. Induction of cephalosporinases can occur with clavulanic acid. Permeability mutants could arise, especially with added pressure from a second beta-lactam.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-lactamase inhibitors from laboratory to clinic. 306 Feb 40

The emergence and spread of ampicillin-resistant Haemophilus influenzae type b strains have led to a sharp reduction in the use of ampicillin, or the addition of chloramphenicol, in the initial therapy of serious childhood infections. In some instances, third generation cephalosporins are used instead. The combination of ampicillin with sulbactam restores the former usefulness of ampicillin and extends its spectrum of activity to include normally ampicillin-resistant Staphylococcus aureus. Sulbactam/ampicillin should be useful in treating bacterial meningitis. It is more effective than third generation cephalosporins against Listeria and enterococci, and is more effective than ampicillin against Enterobacteriaceae. The combination also holds promise as a treatment for soft tissue, bone and joint infections in children.
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PMID:Sulbactam/ampicillin in paediatric infections. 306 53

Sulbactam/ampicillin (Unasyn) possesses the antimicrobial activity of each drug plus the synergistic action and qualities of sulbactam used as a beta-lactamase inhibitor. The combination has a spectrum of activity against many Enterobacteriaceae, Haemophilus species, Branhamella catarrhalis, pathogenic Neisseria species, Acinetobacter anitratus, some pseudomonads, nearly all anaerobes (including Bacteroides), Staphylococcus species, streptococci, and the enterococci. Sulbactam/ampicillin was found to be bactericidal, and its minimum inhibitory concentrations (MICs) affected only by high inoculum concentrations (greater than 10(6) CFU/ml). Fixed ratio in vitro susceptibility tests appear to be preferred, since they best approximate clinical formulations and drug pharmacokinetics. The ratio of 1:1 has been studied, but other ratios such as 1:2 (sulbactam/ampicillin) should be evaluated to promote greater test accuracy. Separate interpretive criteria for most Gram-negative bacteria, Haemophilus, and staphylococci appear unnecessary for some tests.
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PMID:In vitro evaluations of aminopenicillin/beta-lactamase inhibitor combinations. 326 77

Sulbactam/cefoperazone (SBT/CPZ) was used in pediatric patients with acute infections, and the following results were obtained. SBT/CPZ was administered to 18 pediatric patients with acute infections. Out of them, 14 patients, i.e., 3 with acute tonsillitis, 1 with acute laryngitis, 1 with acute bronchitis, 4 with acute pneumonia, 4 with bronchopneumonia, 1 with pyothorax, were adopted for the evaluation, and the other 4 were excluded because they were judged inadequate for clinical efficacy evaluation. The clinical efficacy of SBT/CPZ was assessed as excellent in 4, good in 9 and fair in 1. The effective rate was 92.9%. In 6 cases causative organisms were detected, i.e., Haemophilus influenzae in 3, Klebsiella in 1 and Staphylococcus aureus in 2 cases. Eradication of these organisms was confirmed in all cases except for 1 patient with pyothorax caused by S. aureus. The doses used in 12 out of the evaluated 14 cases ranged from 58.4 to 80 mg/kg/day, 84.1 mg/kg/day was used in 1 case and 101.4 mg/kg/day was used in 1 case with pyothorax. Patients with severe infections were generally given large doses. The frequency of administration was 3 times per day except 1 case, and intravenous drip infusion was used in all cases. The duration of treatment was 2- less than 3 days for 7 cases, 3-5 days for 6 cases and 9 days for 1 case (pyothorax). No clinical side effects were observed in any case. In laboratory examinations, a slight elevation of GOT was observed in 1 case, but no abnormal findings in the other cases. From the above results, SBT/CPZ was considered to be a highly useful drug in the treatment of pediatric infections.
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PMID:[Clinical study on sulbactam/cefoperazone in the field of pediatrics]. 609 60

beta-Lactamase production and susceptibility to an assortment of antimicrobial agents were examined in 9,483 strains of organisms isolated from clinical materials obtained from inpatients and outpatients at 104 institutions throughout Japan from December 1999 to February 2000. The organisms were Staphylococcus aureus, 1,369 strains, including 847 methicillin-resistant (MRSA) strains; Enterococcus faecalis, 735 strains; Enterococcus faecium, 302 strains; Moraxella (Branhamella) catarrhalis, 730 strains; Haemophilus influenzae, 1,142 strains; Escherichia coli, 1,276 strains; Klebsiella pneumoniae, 1,058 strains; Enterobacter cloacae, 772 strains; Serratia marcescens, 847 strains; and Pseudomonas aeruginosa, 1,252 strains. The 23 antimicrobial agents used were ampicillin, sulbactam/ampicillin, clavulanic acid/amoxicillin, oxacillin, piperacillin, cefazolin, cefotiam, cefmetazole, cefoperazone, sulbactam/cefoperazone, cefotaxime, ceftazidime, cefepime, cefpodoxime, imipenem, gentamicin, arbekacin, clarithromycin, minocycline, chloramphenicol, vancomycin, teicoplanin, and levofloxacin. Antimicrobial agents appropriate for each organism were used. Among S. aureus strains, 61.9% were MRSA, and 62.3% were positive for beta-lactamase. Among the MRSA strains, none was resistant to vancomycin or teicoplanin, and only 3% were resistant to arbekacin. There was no vancomycin resistance in the Enterococcus strains. Only 0.1% of E. faecalis strains were ampicillin-resistant. Among the M. catarrhalis strains, 97.5% produced beta-lactamase, while among the H. influenzae strains, 8.5% produced beta-lactamase and 14.5% were beta-lactamase-negative and ampicillin-resistant (BLNAR). Among the Enterobacteriaceae and P. aeruginosa strains, there were 20 (E. coli; 7/1,276, K. pneumoniae; 13/1,058) that produced extended-spectrum beta-lactamases (ESBLs), and 11 that produced class B beta-lactamases. Multiple drug resistance was advanced in every species, and organisms resistant to 7 or more common antimicrobial agents were isolated. The best combination of antimicrobial agent and beta-lactamase inhibitor was sulbactam/cefoperazone. Sulbactam/cefoperazone, cefepime, and imipenem still have excellent antimicrobial activity. Rates of resistance to each antimicrobial agent differed more among institutions than among geographical regions.
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PMID:[beta-lactamase-producing activity and antimicrobial susceptibility of major pathogenic bacteria isolated from clinical samples. Japan beta-lactamase Research Group]. 1259 26


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