Showing papers on "Penicillin published in 1973"

Transmissible Resistance to Penicillin G, Neomycin, and Chloramphenicol in Rhizobium japonicum

Abstract: The genetic basis for resistance to a number of antibiotics was examined in Rhizobium japonicum. Resistance to penicillin G, neomycin, and chloramphenicol appears to be mediated by an extrachromosomal element similar to that found in the Enterobacteriaceae. Resistance to these antibiotics was eliminated from cells by treatment with acridine orange, and resistance to all three antibiotics could be transferred en bloc to Agrobacterium tumefaciens under conditions excluding transformation or transduction as possible genetic mechanisms.

Interaction of Intraleukocytic Bacteria and Antibiotics

Abstract: Bacteria that survive inside polymorphonuclear neutrophils (PMN) following phagocytosis are protected from the bactericidal action of most antibiotics. Two possible explanations are altered metabolism by intraleukocytic bacteria or failure of antibiotics to enter the phagosome. The oxygen consumption of intraleukocytic and extraleukocytic bacteria was measured as an index of bacterial metabolism. PMN respiration and bactericidal activity were suppressed with large doses of hydrocortisone and extraleukocytic bacterial oxygen consumption was abolished by the addition of lysostaphin. Intraleukocytic bacterial continued to consume oxygen suggesting that surviving ingested micro-organisms are metabolically active. Neither penicillin (which cannot kill intraleukocytic bacteria) nor rifampin (which can kill intraleukocytic bacteria) was bactericidal for staphylococci at 5 degrees C. Thus, rifampin is not uniquely able to kill "resting" bacteria.Intraleukocytic or extraleukocytic Staphylococcus aurens were incubated with [benzyl-(14)C]penicillin for 2 h at 37 degrees C. Live intraleukocytic bacteria bound only 13% as much penicillin as live bacteria incubated with killed PMN. To measure the penetration of antibiotics into PMN, [(14)C]rifampin and [(14)C]penicillin were measured in leukocyte pellets and in the supernatant fluid. The total water space in the pellets was quantitated using tritium water and the extracellular water space was measured using Na(235)SO(4). All penicillin associated with the cell pellet could be accounted for in extracellular water. Thus penicillin was completely excluded from the leukocytes. Rifampin was concentrated in the cell pellet 2.2 times when compared with the supernatant concentration. These studies suggest that a likely explanation for the survival of phagocytized bacteria in the presence of high concentrations of most antibiotics is the inability of the antibiotic to enter the phagocyte. Rifampin, which is highly lipid soluble, can enter leukocytes and kill intracellular bacteria.

Chemotherapy of experimental streptococcal endocarditis. I. Comparison of commonly recommended prophylactic regimens.

Abstract: The effectiveness of various antibiotics commonly recommended for the prophylaxis of bacterial endocarditis has been evaluated in experimental streptococcal endocarditis in rabbits. High doses of penicillin G did not prevent the development of this infection. The only consistently successful prophylactic regimens using penicillin alone were those which provided for both an early high serum level and more than 9 h of effective antimicrobial action. Vancomycin was the only other drug which proved uniformly successful when given alone, even though the duration of its antimicrobial action in the blood was only 3 h. However, combined therapy using penicillin G or ampicillin with streptomycin was always effective in prophylaxis. Treatment with single injections of ampicillin, cephaloridine, cephalexin, clindamycin, cotrimoxazole, rifampicin, streptomycin, erythromycin, and tetracycline failed to prevent infection. The findings provide information on the effect of antimicrobials in vivo and may be applicable to the chemoprophylaxis of infective endocarditis in clinical practice.

Multiple Antibiotic Resistance due to a Single Mutation in Neisseria gonorrhoeae

Abstract: A positive correlation (r > +.47, P 1 .01) was found between sensitivities of 147 random clinical isolates of Neisseria gonorrhoeae to all possible pairs of the drugs penicillin, tetracycline, erythromycin, chloramphenicol, acridine orange, and ethidium bromide. High-level resistance to streptomycin was also positively correlated with increased resistance to some of these drugs. This suggested that multiply-resistant strains are not exclusively the result of selection of independent mutants for resistance to each drug and that there may be a common mechanism for resistance to some or all of these drugs. This hypothesis was supported by the demonstration that low-level resistance to a large group of drugs (penicillin, tetracycline, erythromycin, chloramphenicol, rifampin, ethidium bromide, and acridine orange) could be lost as well as restored by a single mutational event in vitro. Resistance of Neisseria gonorrhoeae to antibiotics has gradually become an important practical problem during the last decade [1-6], but there has been almost no scientific inquiry into the genetic and biochemical mechanisms of resistance. Several features of the clinical epidemiology of resistance of the gonococcus to antibiotics aroused our curiosity and prompted these studies. Numerous authors have noted strong positive correlations between sensitivities of individual

Transplacental Passage of Erythromycin and Clindamycin

Abstract: PRESCRIBING antibiotics for pregnant women allergic to penicillin frequently presents a problem because of potential adverse effects — to mother or fetus — and uncertainty of transplacental delivery of antibiotic. Passage of drug into the fetus may or may not be desired. Erythromycin is a good alternative to penicillin for many infections, but it has been suggested that it does not reach the fetus in sufficient concentrations to prevent congenital syphilis.1 Little information on the transplacental passage of clindamycin, which has a spectrum of activity similar to that of erythromycin, is available. The present study was designed to demonstrate whether . . .

Penetration of brain abscess by systemically administered antibiotics

Abstract: ✓ In six consecutive patients treated with systemic antibiotics for brain abscess, chloramphenicol, methicillin, and penicillin were found capable of penetrating the abscess in therapeutic concentration. Nafcillin, a fourth antibiotic tested, failed to penetrate. While on antibiotics, all six patients continued to deteriorate neurologically until needle aspiration of the abscess was carried out, after which recovery began promptly. Organisms were found in the pus despite the presence of therapeutically effective antibiotic levels, and despite the fact that the organisms were sensitive, in vitro, to the antibiotics used. These observations confirm that antibiotics alone are insufficient and that surgical evacuation of the abscess is essential. The need for local instillation of antibiotics directly into abscesses is questionable since penetration following systemic administration of three antibiotics tested was adequate when blood levels were high. It is suggested that the instillation of penicillin or its...

Metabolism of Penicillins to Penicilloic Acids and 6-Aminopenicillanic Acid in Man and Its Significance in Assessing Penicillin Absorption

Abstract: Penicillins can be metabolized to penicilloic acids in man, the extent being dependent on the penicillin structure. In the phenoxy penicillin series, phenoxymethyl penicillin was found to be particularly unstable, but the higher homologues were more stable. In the isoxazolyl series, oxacillin was unstable, and progressive insertion of halogen in the phenyl ring increased stability. Ampicillin and amoxycillin showed some instability, ampicillin possibly being the more stable. After intramuscular administration, carbenicillin was very stable in the body, ampicillin was fairly stable, and benzyl penicillin was unstable. It is important to take into account the penicilloic acid content of urine when estimating total absorption of a penicillin. Increased stability in the body as well as slower renal clearance can lead to high concentrations in the serum. Penicilloic acids seemed to be more slowly cleared from the body than penicillins. The liver is probably the site of inactivation.

Penicillin and gentamicin therapy for enterococcal infections.

Abstract: None of the currently available antibiotic regimens is completely effective for the therapy of severe enterococcal infections. Recent studies have shown that a combination of penicillin plus gentamicin produces enhanced killing against virtually all strains of enterococci in vitro. We report four cases of enterococcal endocarditis and two cases of enterococcal meningitis that were successfully treated with penicillin and gentamicin, thus confirming the in vivo effectiveness of this combination of antibiotics against enterococci.

Penicillin Reactions Among Patients in Venereal Disease Clinics: A National Survey

Abstract: To determine the nature, incidence, and trend of penicillin reactions among patients in veneral disease clinics, four cooperative surveys were conducted at five-year intervals. In the 1969 survey, 6.6% of 36,048 patients questioned claimed sensitivity to penicillin. Of 27,673 patients treated with penicillin, 0.66% experienced a penicillin reaction, the most frequent allergic reaction being urticaria. The incidence of anaphylaxis was 0.04%. During the four survey periods, one death occurred in 94,655 patients treated with penicillin. Since 1959, the incidence of penicillin reactions among venereal disease clinic patients has decreased.

Clinical experiences with cefazolin and other cephalosporins in bacterial endocarditis.

Abstract: Eleven patients with bacterial endocarditis were treated with cefazolin, a new cephalosporin antibiotic. The antibiotic was well tolerated, and high levels in blood were achieved without accumulation of the drug or toxicity. Nine of the patients with endocarditis due to Staphylococcus aureus and one with endocarditis due to Bacillus species were cured. One patient with staphylococcal endocarditis failed to respond to cefazolin. Although the organism isolated from this patient was sensitive to cefazolin when a small inoculum was used, tests of susceptibility with a large inoculum showed resistance to cefazolin. The results with cefazolin in the present study and the recorded experience with cephalothin, cephaloridine, and cephalexin indicate that these agents may be used as effective substitutes for penicillin and penicillin derivatives in the treatment of staphylococcal and streptococcal (not enterococcal) endocarditis when penicillin is contraindicated.

Antigenicity and Cross-Reactivity of Penicillins and Cephalosporins

Abstract: edge of immunogenicity of penicillins and cephalosporins and their allergic cross-reactivity. The topics to be covered are (1) immunogenicity of penicillin, (2) immunogenicity of cephalosporins, and (3) immunologic and allergic cross-reactivity. Immunogenicity of penicillins. Most of the work has been done with benzylpenicillin (penicillin G, BP), although much of the information derived from these studies is probably applicable to semisynthetic penicillins as well. To determine the nature of immune responses of man to BP, it was first necessary to study the haptenic determinants of BP hypersensitivity, and then to synthesize the appropriate multivalent and univalent haptens. On the basis of knowledge of the chemical reactions of BP, particularly of its hydrolysis and aminolysis in aqueous solution at physiological pH levels, it was possible to postulate that the benzylpenicilloyl (BPO) groups would be an important haptenic determinant [1]. Proper haptenic reagents containing BPO groups were synthesized and tested for immunologic reactivity against sera from humans with penicillin allergy and from rabbits immunized with BP emulsified in Freund's adjuvant. It was found that immune rabbit sera gave classical precipitin reactions with multivalent BPO conjugates of protein and of polylysine carriers [1-4]. Proof of haptenic specificity was obtained by specific inhibition of this immunologic reaction by dilute solutions of defined crystalline univalent BPO-haptens. In addition to precipitin reactions, BPO specificity of human and rabbit antibodies could be proved by use of passive cutaneous anaphylaxis (PCA), passive hemagglutination, direct skin reactions for wheal-and-flare reactivity in man, Prausnitz-Kiistner (PK) tests and others, with hapten inhibition. In addition, cellular hypersensitivity reactions specific for the BPO-hapten (and also showing carrier specificity) could be demonstrated. Penicilloyl multivalent haptens were synthesized from several semisynthetic penicillins (dimethoxyphenyl penicillin, aaminobenzylpenicillin, oxacillin, etc.) and with these defined conjugates, the extent of crossreactivity in various situations could be investigated. Studies in animals and humans showed that, in general, there was cross-reactivity. This varied among the penicilloyl haptens, e.g., the benzyl(BP) and a-aminobenzyl(ampicillin) penicilloyl haptens cross-reacted extensively, whereas benzyl (BP) and dimethoxyphenyl (methicillin) or oxacilloyl (oxacillin) penicilloyl haptens generally cross-reacted only slightly. Furthermore, there was considerable heterogeneity among sera or individuals, e.g., some populations of antibody to BPO were much more cross-reactive than others. The basis for heterogeneity in cross-reactivity is not clear. It may be influenced by the molecular specificity of the combining regions, i.e., which part of the molecule is best recognized, the side chain or the thiazolidine nucleus. It may be influenced by binding avidity. It may conceivably be influenced by the flexibility or rigidity (i.e. conformability) of the special combining regions. These uncertainties notwithstanding, it is clear that there is extensive heterogeneity in cross-reactivity to homologous penicilloyl determinants among different sera or individuals having BPO-specific antibodies.

Susceptibility of Bacteroides fragilis to Six Antibiotics Determined by Standardized Antimicrobial Disc Susceptibility Testing

Abstract: The susceptibility of 100 or more strains of Bacteroides fragilis to six antibiotics was determined by standardized agar dilution and disc diffusion tests. Good correlation of results of the two methods was obtained with chloramphenicol, clindamycin, lincomycin, penicillin, and vancomycin. Correlation of results with erythromycin was not as good. A great deal of overlapping of zone diameters among strains classed as susceptible, intermediate, and resistant occurred with both erythromycin and lincomycin, making interpretation of disc diffusion tests difficult. All strains tested were susceptible to chloramphenicol; 94% were susceptible to clindamycin at concentrations readily achieved with ordinary dosage, and all strains were inhibited by 6.2 μg/ml, a level which is achieved with somewhat more intensive therapy. Only 7% were shown to be susceptible to erythromycin and 13% to lincomycin under the conditions of our testing procedure. Only a small percentage of the strains were susceptible to penicillin, and none was susceptible to vancomycin.

Penicillin-Tobramycin Synergism Against Enterococci: a Comparison with Penicillin and Gentamicin

Abstract: Combinations of penicillin plus tobramycin have been compared with penicillin plus gentamicin against 27 strains of enterococci isolated from blood cultures. Penicillin plus gentamicin was synergistic against all strains. The combination of penicillin plus tobramycin was equally effective against strains of Streptococcus facalis, but was ineffective against all four strains of S. faecium tested.

Group D streptococcal bacteremia, with emphasis on the incidence and presentation of infections due to Streptococcus bovis.

Abstract: Procedures routinely in use in many hospital microbiology laboratories do not distinguish between enterococci and nonenterococcal Group D streptococci. During a 15-month period we observed 11 patients with bacterial endocarditis due to Group D streptococci, eight of which were due to the nonenterococcal species, Streptococcus bovis. This micro-organism showed in vitro susceptibility to a wide variety of antimicrobial agents, including oxacillin and lincomycin. In patients with S. bovis infection, high serum bacteriostatic and bactericidal levels were achieved with penicillin or clindamycin alone, or penicillin and an aminoglycoside. The clinical response was equivalent with all drug regimens. In contrast, enterococci were more resistant in vitro to antibiotics, and in vivo definitely lower serum bactericidal activity was achieved. Infections due to S. bovis are probably often misdiagnosed. It is of clinical importance to distinguish S. bovis from the enterococci because therapy for the former spe...

Cephalosporinase Activity in Bacteroides fragilis

Abstract: Cephalosporinase activity was demonstrated in all of 10 strains of Bacteroides fragilis investigated. Low rates of hydrolysis of cephalosporins (0.25 to 3.5 mumol of cephaloridine per h per 10(9) cells) were found, but no activity against penicillin substrates was detected. In two strains the cephalosporinase activity was increased 40-and 80-fold by growing cells in the presence of penicillin. No permeability barrier for these antibiotics was demonstrated. In most cases the substrate profile showed decreasing activity in the following order: cephaloridine > cephalothin > cephaloglycin > cephalexin. The cephalosporinase from these organisms differed from that found in facultative and aerobic gram-negative bacilli in that it was inhibited by both cloxacillin and p-chloromercuribenzoate. Among nine strains of Bacteroides fragilis subspecies fragilis, correlation was found between in vitro resistance to cephaloridine and amount of beta-lactamase activity in sonically disrupted cells.

Comparative In Vitro Activity of Three Aminoglycosidic Antibiotics: BB-K8, Kanamycin, and Gentamicin

Abstract: Kanamycin, BB-K8, and gentamicin were tested in parallel against 1,037 bacterial strains isolated from clinical material. The activity of BB-K8 at 20 μg/ml was comparable to that of gentamicin at 8 μg/ml against Pseudomonas aeruginosa and against Enterobacteriaceae, with the exception of gentamicin-resistant strains of Proteus rettgeri and Providencia stuartii, in which case the activities of BB-K8 and kanamycin were the same. BB-K8 exhibited little or no activity against streptococci. The activity of BB-K8 was affected by pH and inoculum size. A regression graph for inhibition data with a 10-μg disk of BB-K8 was developed, and synergistic activity of penicillin and BB-K8 against Streptococcus faecalis was tested.

The susceptibility of bacteroides fragilis to 24 antibiotics

Abstract: Of the anaerobic, nonsporulating, gram-negative bacilli, those of the genus Bacteroides are most frequently associated with serious infections in man. Forty clinical isolates of the species Bacteroides fragilis were tested quantitatively against 24 antibiotics by an agar-dilution method under anaerobic conditions. Clindamycin, the most active antibiotic studied, had a median MIC of 0.19 ng/ml. Rifampin, erythromcyin, lincomycin, and chloramphenicol also inhibited all isolates in clinically attainable concentrations. More than half of the strains tested were resistant to tetracycline. Some isolates were susceptible to penicillin G, ampicillin, carbenicillin, and the cephalosporins, and all were resistant to the aminoglycosides, polymyxins, and semisynthetic penicillinase-resistant penicillins. The genus Bacteroides consists of nonsporulating, gram-negative bacilli which are obligate anaerobes. These organisms predominate numerically in the normal bacterial flora of the large bowel and are important components of the normal flora of the oral cavity and the urogenital tract [1]. Although they have long been recognized as significant human pathogens, the literature on infec

Transient Perceptive Deafness due to Erythromycin Lactobionate

Abstract: To the Editor.— Erythromycin may cause adverse reactions of two types: (1) allergic such as fever, eosinophilia, skin eruptions, and cholestatic hepatitis, 1-3 or (2) toxic such as epigastric distress, nausea, vomiting, and diarrhea. 4 We observed two patients who developed transient bilateral perceptive deafness following intravenous administration of erythromycin lactobionate. Report of Cases.— Two women, 65 and 67 years old, were recently admitted to our medical department and found to have subacute bacterial endocarditis superimposed on valvular heart disease. One patient was known to be allergic to penicillin, and the other developed nausea and vomiting while receiving penicillin. The first patient, given 2.1 gm erythromycin administered intravenously for two days and 4.2 gm during 12 hours on the third day, complained of loss of hearing three hours after termination of the infusion. The second patient, who, after penicillin treatment was discontinued, was given 4.2 gm erythromycin intravenously administered during

Fluorescence and circular dichroism studies on the Streptomyces R61 DD-carboxypeptidase-transpeptidase. Penicillin binding by the enzyme.

Abstract: The circular dichroism of the dd-carboxypeptidase–transpeptidase from Streptomyces R61 shows in the near u.v. a set of weak extrema at 289nm (positive) and at 282, 275 and 268nm (all negative). In the far u.v. it shows negative extrema at 217–218 and 208nm, crossover at 202nm and a positive maximum at about 194nm. The u.v. absorption of the enzyme shows it to contain tyrosine and tryptophan in approx. 3.4:1 ratio. The enzyme is fluorescent with a maximum emission at 318–320nm. The near-u.v. circular dichroism of the protein is extensively affected by binding of penicillin G, but the far u.v. is unaffected. Binding of the antibiotic also causes quenching of the fluorescence of the enzyme. The latter effect has been used to study the binding of penicillin G to the enzyme and the influence exerted upon it by salts, denaturants and peptide substrates and inhibitors. High-affinity binding of penicillin appears to be comparatively slow and reversible, and can occur under conditions in which the protein is enzymically inactive. The thermal denaturation of the enzyme in guanidinium chloride at pH7 is affected by binding of the antibiotic. The presence of even large concentrations of β-mercaptoethanol neither impaired the activity of the enzyme nor prevented its inhibition by penicillin G or cephalosporin C. A new hypothesis for the molecular mechanism of the interaction of the enzyme with penicillin is proposed.

Ampicillin rash in children. Relationship to penicillin allergy and infectious mononucleosis.

Abstract: Of 370 children receiving ampicillin, 35 (9.46%) developed a skin rash. Nineteen of these children and 19 who received ampicillin but did not develop rash were observed. One patient from each group had serologic evidence of Epstein-Barr virus infection. No child with ampicillin rash had a positive skin test to ampicillin or penicillin major or minor determinants. Fourteen children with rash continued ampicillin therapy with no ill effects and with disappearance of the rash while still receiving the drug. These observations indicate that subclinical infectious mononucleosis does not commonly accompany ampicillin rash and suggest that patients with ampicillin rash are not at significant risk to develop life-threatening immediate or accelerated reactions to subsequent ampicillin or penicillin therapy. The possibility remains that skin rashes and other delayed reactions might occur with repeated drug exposure.

Streptococcal Pharyngitis Therapy: Comparison of Clindamycin Palmitate and Potassium Phenoxymethyl Penicillin

Abstract: Clindamycin palmitate and potassium phenoxymethyl penicillin were evaluated in 103 children with upper respiratory illnesses and pharyngeal group A streptococci, from November 1970 to July 1971. The children were assigned randomly by weight to one of the antibiotic regimens given orally for 10 days. Clindamycin palmitate and potassium phenoxymethyl penicillin dosages were 75 and 125 mg, respectively, in 5 ml tid for children weighing less than 25 kg, and 150 and 250 mg, respectively, in 10 ml bid for children weighing 25 kg or more. Recurrences of the original streptococcal group A, M, and T types within 3 weeks after the end of treatment were classified as failures. The failure rates were: clindamycin palmitate, 10% (5 of 52), and potassium phenoxymethyl penicillin, 18% (9 of 51). Possible drug-related rashes were observed in 8 of 52 clindamycin palmitate-treated patients. The geometric mean minimal inhibitory concentrations of clindamycin and penicillin against 103 isolates of group A streptococci were 0.033 and 0.007 μg/ml, respectively. The serum concentrations about 70 min after ingesting 150 mg of clindamycin palmitate averaged 3.8 μg/ml and after 250 mg of potassium phenoxymethyl penicillin averaged 0.9 μg/ml. Clindamycin palmitate was as effective as potassium phenoxymethyl penicillin in eradicating group A streptococci from the pharynx in tid and bid regimens. Nevertheless, because of its rash-producing tendency in some patients and higher cost, clindamycin palmitate should not be preferred to penicillin for treatment of streptococcal sore throat in the non-penicillin-allergic patient.