Showing papers on "Penicillin published in 1980"

Penicillin-binding proteins of multiply antibiotic-resistant South African strains of Streptococcus pneumoniae.

Abstract: Multiply drug-resistant South African pneumococci (with penicillin minimal inhibitory concentrations ranging from 0.2 to 12.5 microgram/ml) showed several types of major alterations in their penicillin-binding protein (PBP) pattern compared with that of a penicillin-susceptible laboratory strain of Streptococcus pneumoniae (R6; penicillin minimal inhibitory concentration = 0.006 microgram/ml). Genetic transformants were obtained by using South African pneumococcus (strain 8249) deoxyribonucleic acid as donor and the competent cells of strain R6 as recipient; seven classes of transformants with progressively higher penicillin resistance were isolated, and their PBPs were tested. The PBP patterns exhibited a gradual shift from a pattern similar to that of the recipient to a pattern resembling that of the donor strain as the level of penicillin resistance increased.

Multiple changes of penicillin-binding proteins in penicillin-resistant clinical isolates of Streptococcus pneumoniae.

Abstract: Penicillin-binding properties and characteristics of penicillin-binding proteins (PBPs) were investigated in several clinical isolates of Streptococcus pneumoniae differing in their susceptibilities to penicillin (minimal inhibitory concentration [MIC], 0.03 to 0.5 microgram/ml) and compared with the penicillin-susceptible strain R36A (MIC, 0.07 microgram/ml). Several changes accompanied the development of resistance: the relative affinity to penicillin of whole cells, isolated membranes, and two major PBPs after in vivo or in vitro labeling decreased (with increasing resistance). Furthermore, one additional PBP (2') appeared in four of five relatively resistant strains with an MIC of 0.25 microgram/ml and higher. PBP 3 maintained the same high affinity toward penicillin in all strains under all labeling conditions.

Penicillin-binding proteins in bacteria.

Abstract: The penicilllin-binding proteins (PBPs) of several gram-positive and gram-negative bacteria have been examined. The results indicate that: (i) PBPs are membrane proteins with molecular weights ranging from 40,000 to 120,000. When extracted with Triton X-100 from sonicated cells, they appear to fall into two patterns: one found in rods and the other in spheres. A major difference is in the low-molecular-weight component, which is usually the major PBP in bacilli but a minor one in cocci. (ii) There is a wide variation in both the number and the amount of PBPs in different bacteria, and taxonomically related bacteria tend to have similar PBP patterns. These patterns often correlate with the affinity of PBPs for penicillin and other beta-lactam antibiotics. (iii) The low-molecular-weight component usually releases penicillin spontaneously with a half-life of 10 min or less. Most, but not all, PBPs release bound penicillin in the presence of neutral hydroxylamine (0.2 to 0.8 M).

Penicillin-binding proteins of penicillin-susceptible and intrinsically resistant Neisseria gonorrhoeae.

Abstract: The penicillin-binding proteins (PBPs) of Neisseria gonorrhoeae were investigated by using [3H]benzylpenicillin of high specific activity. This made it possible to label the PBPs both in cytoplasmic membranes and in the membranes of actively growing cells (in vivo labeling). A total of 20 strains isolated from different geographic locales showed the same pattern of three major PBPs, which had molecular weights of approximately 90,000, 63,000, and 48,000. Five clinical isolates of intrinsically penicillin-resistant gonococci each exhibited reduced penicillin binding of PBPs 1 and 2. The construction of an isogenic set of transformants with increasing levels of penicillin resistance indicated that the penA gene was associated with a decrease in penicillin binding fo PBP 2. Decreased binding to PBP 1 is likely to accompany the newly reported pem and tem genes, which govern to highest level of penicillin resistance.

Carbenicillin and Penicillin G Inhibit Platelet Function In Vitro by Impairing the Interaction of Agonists with the Platelet Surface

Abstract: Carbenicillin or penicillin G administered in large doses can cause a bleeding diathesis as a result of platelet dysfunction. These antibiotics also inhibit platelet aggregation in vitro, although several-fold larger concentrations of drug are required to demonstrate this effect. We wondered whether these antibiotics might impair platelet function by interfering with the initial step of platelet activation: the binding of agonists to their specific receptors on the platelet surface.Platelet aggregation and [(14)C]serotonin release induced by epinephrine were competitively inhibited by carbenicillin and penicillin G in vitro. At antibiotic concentrations that inhibited platelet function by more than 80%, the affinity of platelet alpha-adrenergic receptors for the alpha-adrenergic antagonist, [(3)H]dihydroergocryptine, and for epinephrine was reduced twofold by carbenicillin and sixfold by penicillin G (P < 0.01). Platelet aggregation and [(14)C]serotonin release stimulated by ADP were also competitively inhibited by these antibiotics. In addition, carbenicillin reduced the incorporation of an ADP affinity label, 5'-p-fluorosulfonylbenzoyl [(3)H]adenosine, into its binding protein in platelet membranes. Moreover, both carbenicillin and penicillin G impaired the interaction of von Willebrand factor with platelets as evidenced by their inhibition of the agglutination of formalin-fixed platelets by ristocetin, snake venom, or bovine factor VIII. These studies demonstrate that carbenicillin and penicillin G inhibit platelet function in vitro by impairing the interaction of several agonists with their specific receptors on the platelet surface membrane. If this were mechanism operative in vivo, it could account for the hemorrhagic as well as the potential antithrombotic effects of these antibiotics.

Single-dose penicillin prophylaxis against neonatal group B streptococcal infections. A controlled trial in 18,738 newborn infants.

Abstract: Neonatal Group B streptococcal infections may not respond to antimicrobial therapy and have been associated with case fatality rates of 50 per cent or greater. We evaluated the effect on colonization and disease rates of a single intramuscular dose of aqueous penicillin G given at birth in a prospectively controlled study of 18,738 neonates during a 25-month period. The colonization rate in the mothers was 26.6 per cent, with 50 per cent concordance in the untreated infants and 12.2 per cent in the penicillin-treated infants (P<0.001). There was a significant decrease in the incidence of disease caused by all penicillin-susceptible organisms in the penicillin group (0.64 vs. 2.26 cases per thousand live births, P=0.005). Disease caused by penicillin-resistant pathogens was increased in the penicillin-treated group during the first year of the study but was unaffected during the second year. Routine administration of parenteral penicillin at birth cannot be recommended until the effect on the inci...

β-Lactamase Activity in Human Pus

Abstract: Pus was obtained from patients with polymicrobial intraabdominal abscesses or polymicrobial empyema. Physical and chemical characteristics of 12 specimens were examined, and bacterial isolates were enumerated. Pus supernatant of six specimens rapidly inactivated penicillin, cephalothin, and cefazolin. Carbenicillin and ticarcillin were similarly degraded by supernatant of certain pus specimens. Cefoxitin, chloramphenicol, and clindamycin were not appreciably inactivated by pus supernatant. Degradation of penicillin and cephalosporin congeners in pus was due to the presence of beta-lactamase, as shown by chemical interaction with nitrocefin, chromatography, and inhibition by the beta-lactamase inhibitor clavulanic acid. Pus supernatant containing beta-lactamase activity reduced the bactericidal activity of carbenicillin against Bacteroides fragilis in whole pus in an abscess model in vitro. Bactericidal activity of clindamycin or cefoxitin was not impaired in pus containing beta-lactamase.

Antibiotic-resistant Staphylococcus epidermidis in patients undergoing cardiac surgery.

Abstract: Staphylococcus epidermidis isolates containing subpopulations resistant to 100 microgram of methicillin per ml were found on the chests of only 3 of 80 (4%) patients before cardiac surgery, whereas these highly resistant staphylococci were isolated from the chest wounds of 43 of 80 (54%) patients 5 days postoperatively. The percentage of patients colonized with methicillin-resistant S. epidermidis increased with time postoperatively. Methicillin-resistant postoperative isolates also contained organisms resistant to other antibiotics frequently used during these patients' hospitalizations. The percentages of patients with organisms resistant to various antibiotics were: nafcillin (100%), penicillin (100%), cephalothin (93%), cefamandole (80%), streptomycin (67%), and gentamicin (20%). Preoperative methicillin-susceptible isolates were generally susceptible to other antibiotics. Two patients with S. epidermidis prosthetic valve endocariditis caused by multiple antibiotic-resistant isolates were among the study patients. Antibiotic susceptibility patterns of each isolate from these two patients were identical to those of postoperative chest isolates from the same patient.

Biochemical and genetical approaches to the mechanism of action of penicillin.

Abstract: Since the discovery in 1965 that penicillin inhibits the transpeptidation reaction in peptidoglycan synthesis, a considerable effort has been put into the purification of enzymes that catalyse this reaction. This has resulted in the recognition that bacteria possess multiple forms of these penicillin-sensitive enzymes and has made it difficult to identify the precise target that penicillin inactivates to kill the organism. Recently penicillin-sensitive enzymes have been detected and studied as penicillin-binding proteins on sodium dodecyl sulphate polyacrylamide gels. The availability of this convenient method for identifying penicillin-sensitive enzymes has allowed biochemical and genetical approaches to be used to dissect their roles in the lethal effects of penicillin and other β-lactam antibiotics. Three penicillin-binding proteins (1B, 2 and 3) have been identified as killing targets for penicillin in Escherichia coli , whereas four other binding proteins are not implicated in the mechanism of action of the antibiotic. The complex biological effects that β-lactam antibiotics produce on the growth of E. coli can be explained by their interaction with the three killing targets. Progress in the correlation of penicillin-binding proteins with penicillin-sensitive enzymes and in the development of strains of E. coli that overproduce penicillin-binding proteins is discussed.

CP-45,899 in combination with penicillin or ampicillin against penicillin-resistant Staphylococcus, Haemophilus influenzae, and Bacteroides.

Abstract: CP-45,899 is a new, semisynthetic beta-lactamase inhibitor. When tested alone, CP-45,899 displayed only weak antibacterial activity, with the notable exception of its potent action against penicillin-susceptible and -resistant Neisseria gonorrhoeae. A combination of 3.12 microgram of CP-45,899 per ml with 3.12 microgram of ampicillin per ml, tested in broth cultures, inhibited ca. 90% of resistant Staphylococcus and Haemophilus influenzae strains; similar data were obtained in a variety of media. The same combination of CP-45,899 with ampicillin or penicillin G inhibited 90% of Bacteroides fragilis as interpreted from agar dilution minimal inhibitory concentrations. Inhibitory concentrations of CP-45,899-ampicillin were bactericidal against H. influenzae strains and were as bactericidal as nafcillin or cephalothin against S. aureus. Ampicillin-resistant S. aureus, H. influenzae, and B. fragilis strains did not develop resistance to CP-45,899-ampicillin when transferred as many as six passages in the presence of a sublethal concentration of the combination.

In vitro antimicrobial susceptibility of Actinobacillus actinomycetemcomitans.

Abstract: The agar dilution technique was used for determination of the antibiotic susceptibilities of 57 oral isolates and 2 nonoral isolates of Actinobacillus actinomycetemcomitans. Tetracycline, minocycline, and chloramphenicol inhibited more than 96% of the strains tested at a concentration of less than or equal to 2 micrograms/ml; 89% of the strains were inhibited by 2 micrograms of carbenicillin per ml. The other antimicrobial agents tested were less active. Approximately 10% of the A. actinomycetemcomitans strains were resistant to ampicillin, erythromycin, and penicillin G at concentrations of 32 to 64 micrograms/ml. These data suggest that tetracycline and minocycline may be valuable drugs in the treatment of A. actinomycetemcomitans infections.

Failure of penicillin G benzathine in the treatment of neurosyphilis.

Abstract: • Although penicillin remains highly effective in syphilis, important questions exist regarding the optimal regimen for syphilitic involvement of the nervous system. Progression of neurosyphilis despite 7.2 million units of penicillin G benzathine occurred in the case reported here, with subsequent resolution following high-dose intravenous aqueous penicillin therapy. This and other recent reports support the conclusion that neurosyphilis should be treated with higher amounts of penicillin than is provided by the benzathine regimens. (Arch Intern Med 140:1117-1118, 1980)

Penicillin concentrations in cerebrospinal fluid after different treatment regimens for syphilis.

Abstract: The concentrations of penicillin in the cerebrospinal fluid (CSF) were compared simultaneously with those in the serum in 17 patients with syphilis. The antibiotic concentrations were measured by the agar well diffusion method. There were no detectable concentrations of penicillin in the CSF after administration of benzathine penicillin 2.4 megaunits, benzathine penicillin 7.2 megaunits, procaine penicillin in aluminium monostearate (PAM) 12 megaunits, or aqueous procaine penicillin G 2.4 megaunits. Only after high doses of aqueous penicillin G 24 megaunits daily or aqueous penicillin G 2 megaunits daily together with oral probenecid 2 g daily was penicillin detectable in the CSF. The concentrations after the latter regimen were the highest and much higher than the minimum inhibitory concentration for Treponema pallidum.

Relative Resistance to Penicillin in the Pneumococcus: A Prevalence and Case-Control Study

Abstract: Isolates of Streptococcus pneumoniae from 103 patients were submitted for serotyping and determination of the minimum inhibitory concentration (MIC) for penicillin. Isolates from 16 patients were relatively resistant to penicillin (MIC, 0.1 to 0.5 μg/ML). In a study to determine if the patients with relatively resistant pneumococci (RRP) differed from patients with normally susceptible pneumococci, 18 patients with RRP showed no significant difference from their matched controls in antibiotic use during the two months prior to isolation of the pneumococcus. Other variables that showed no significant difference between the two groups were (1) antibiotic use in household contacts in the previous six months, (2) presence of chronic infection in the case or control patient, and (3) recurrence of pneumococcal infection following therapy. The high rate of relative resistance to penicillin is heretofore unknown in a general, unconfined population in this country. The case-control study suggests that no strong relationship exists between isolating RRP and prior penicillin administration. More extensive surveys in the United States are needed. ( JAMA 243:1824-1827, 1980)

Antibiotic Susceptibility of Beta-Lactamase-Producing Strains of Branhamella (Neisseria) catarrhalis

Abstract: All 11 clinically significant isolates of Branhamella catarrhalis examined in this study were found to produce β-lactamase The enzyme was apparently not plasmid associated since extrachromosomal deoxyribonucleic acid was not detected in any of the strains The β-lactamase activity of all strains was significantly depressed by the β-lactamase inhibitors clavulanic acid and CP 45899 Based on comparisons of relative susceptibility to various β-lactam antibiotics, it was inferred that the β-lactamase of B catarrhalis was significantly more active against penicillin congeners than against cephalosporin congeners Most strains were not inhibited by readily achievable serum concentrations of the pencillinase-sensitive penicillins, penicillin G, ampicillin, and amoxicillin Methicillin was equally ineffective With rare exceptions, most strains of B catarrhalis were inhibited by achievable serum concentrations of seven cephalosporins (cephalothin, cephapirin, cephaloridine, cephalexin, cephamandole, cefaclor, and cefuroxin) and one cephamycin (cefoxitin) All strains were uniformly resistant to clindamycin but were inhibited by achievable serum concentrations of erythromycin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole Comparison of geometric mean minimum inhibitory concentrations of all antimicrobial agents tested suggested that B catarrhalis was most susceptible to cefoxitin, erythromycin, and tetracycline

Treatment of experimental staphylococcal infections: effect of rifampin alone and in combination on development of rifampin resistance.

Abstract: Rifampin is a potentially useful anti-staphylococcal agent, but resistance develops frequently when the drug is used alone. The efficacy of rifampin, trimethoprim, and a penicillin alone or in combination was examined in mice with acute or subacute infections. Mice were infected intraperitoneally with penicillin-susceptible Staphylococcus aureus. Survival after penicillin therapy was only 9.1% in contrast to survival after rifampin therapy which was 68% (P less than 0.001). No rifampin-resistant S. aureus were isolated from peritoneal fluid or heart blood samples from dead animals in these short-term experiments. Rifampin was ineffective (survival, 4.8%) for infections instituted with rifampin-resistant strains. Long-term experiments were conducted after intravenous injection of 4 x 10(8) S. aureus. Forty percent of the animals survived after methicillin therapy; 77% survived after rifampin therapy (P less than 0.001). However, 40% of those animals that died after rifampin therapy died with rifampin-resistant organisms. No animal dying in groups treated with a combination of rifampin and trimethoprim (85% survival) or rifampin and methicillin (79% survival) died with rifampin-resistant organisms. Thus, rifampin combined with a penicillin or trimethoprim was effective in preventing the development of rifampin-resistant strains.

Penicillin allergy: anti-penicillin IgE antibodies and immediate hypersensitivity skin reactions employing major and minor determinants of penicillin.

Abstract: 300 children considered to have had adverse reactions to penicillin were examined. Informed consent was obtained from the parents. Skin tests were conducted by the scratch/prick and intradermal techniques, using benzylpenicilloyl polylysine conjugate and a mixture of minor determinants of penicillin. Specific anti-penicillin IgE antibodies were estimated by the radioallergosorbent test. There was a good correlation between the two methods. The overall frequency of positive tests was 19%. 11 children showed cutaneous reactivity only to the minor determinants mixture. Positive results were found more often in those with accelerated adverse reactions, particularly anaphylaxis, serum sickness, angio-oedema, or urticaria. The validity of penicillin-negative results was confirmed by drug challenge in 56 subjects, only 2 of whom showed a slight skin rash. Of 5 patients with positive tests, inadvertent administration of penicillin produced accelerated urticaria in all. 14 of 42 children with positive tests had lost hypersensitivity to penicillin one year later. In a separate group of 50 children with a history of adverse response to ampicillin, the overall frequency of positive tests was 12%; 38% showed evidence of recent E-B virus infection. It was concluded that penicillin allergy is often overdiagnosed. The diagnosis can be reliably confirmed by skin tests using major and minor determinants of benzylpenicillin and by the radioallergosorbent test; such hypersensitivity is not permanent.

A Review of Positive Blood Cultures: Identification and Source of Microorganisms and Patterns of Sensitivity to Antibiotics

Abstract: All strains of bacteria and fungi isolated from blood cultures of patients hospitalized in a large primary and tertiary care center were studied prospectively for determination of their clinical significance and probable source. In some instances the immediate mortality rate was also determined. The sensitivity patterns of all aerobic organisms to antibiotics were studied in relation to the role of antibiotic therapy. A positive culture was obtained from 6.8% of all blood specimens cultured and these positive cultures represented 639 episodes of bacteremia or fungemia. The organism isolated most of ten was Escherichia coli, and the most common known source was the urinary tract. Anaerobic organisms were isolated from 9.2% of the episodes of bacteremia, with the bowel being the most common probable source of infection. Antibiotic sensitivity testing revealed that all staphylococci were sensitive to methicillin, but only 22% were sensitive to penicillin. No penicillin-resistant pneumococci were encountered. The Enterobacteriaceae exhibited such a high sensitivity to gentamicin that comparison of its activity with that of other, newer aminoglycosides was impossible.

The Penicillin‐Binding Proteins in Streptococcus faecalis ATCC 9790

Abstract: Streptococcus faecalis ATCC 9790 possesses seven membrane-bound penicillin-binding proteins. They have been characterized with respect to their apparent molecular weights, relative abundance, specificity profiles for 15 different β-lactam antibiotics and stability under various conditions. In water and at 37°C, all the native penicillin-binding proteins have half-lives longer than 20 h except protein 3b (half-life of about 600 min) and protein 4 (half-life of about 175 min). The short-lived 80000-Mr protein 4 is spontaneously converted into a 73000-Mr water-soluble, penicillin-binding protein 4*. Similarly, the short-lived 82000-Mr protein 3b seems to be the protein from which the 72000-Mr water-soluble protein X spontaneously originates during incubation of the membranes. Release of both proteins 4* and X from the membrane is maximal under alkaline conditions; it is not inhibited by various protease inhibitors. After exposure to trypsin, the 43000-Mr membrane-bound penicillin binding protein 6 (a DD-carboxypeptidase) gives rise to a 30000-Mr water-soluble protein 6*. Like the parent protein, protein 6* exhibits both DD-carboxypeptidase activity and penicillin-binding ability. With proteins 6 and 6*, low dose levels of p-chloromercuribenzoate prevent both enzyme activity and combination with penicillin, thus strongly suggesting that a thiol group is involved in the enzyme active center. We have shown previously [Coyette et al. in Eur. J. Biochem. 88, 297–305 (1978) and 75, 231–239 (1977)] that the DD-carboxypeptidase protein 6 fragments the benzylpenicillin molecule with formation of phenylacetylglycine. Breakdown of the complex formed between [14C]benzylpenicillin and the 140000-Mr membrane-bound protein 1 is also ‘enzyme-catalysed’. Most likely, however, the released product is penicilloate. With all the other penicillin-binding proteins whose molecular weights are intermediate between those of proteins 1 and 6, breakdown of the complexes formed with [14C]benzylpenicillin results from proteolysis and is not due to the release of the bound metabolite. None of the penicillin-binding proteins behaves, by itself, as a lethal target for β-lactam antibiotic action on the living cells.

The endotoxin-liberating effect of antibiotics on meningococci in vitro .

Abstract: Three strains of Neisseria meningitis (two endotoxin-liberating and one in vitro variant non-liberating) were studied during treatment with MIC and 100 times MIC values of benzylpenicillin and chloramphenicol in a chemically-defined, protein-free medium. Treatment with the highest dose of benzylpenicillin had the most rapid effect on meningococci, although the antibacterial effect was the same for the two penicillin concentrations after 20 h. Chloramphenicol treatment showed a much slower antibacterial effect. After 2 h of antibacterial treatment, an increase of filtrable endotoxin in the medium was found for the endotoxin-ligerating strains only when the highest penicillin dose was used. During the same period there was a rapid cell death. After 20 hours of treatment, however, the endotoxin-liberating strains treated with high and low concentrations of penicillin had a markedly reduced content of filtrable endotoxin, compared to the controls and to the cultures treated with chloramphenicol. Antibacterial treatment had no, or only minimal, effect on the total content of endotoxin in the cultures, compared to the untreated controls. The endotoxin non-liberating strain had about the same total content of endotoxin as the liberating strains, but did not liberate filtrable endotoxin into the medium unless filtered with a much higher pressure through a filter with smaller pore size.