Showing papers on "Penicillin published in 1976"

Susceptibility of Anaerobic Bacteria to 23 Antimicrobial Agents

Abstract: The antimicrobial susceptibility of 492 anaerobic bacteria, the majority of which were recent clinical isolates, was determined by the agar dilution technique. Penicillin G was active against most of the strains tested at 32 U or less/ml, but only 72% of Bacteroides fragilis strains were susceptible at this level and 9% required 256 U or more/ml. Ampicillin was effective against most of the strains except B. fragilis at 16 mug or less/ml. Amoxicillin was active against only 31% of B. fragilis, 76% of other Bacteroides species, and 67% of Fusobacterium species at 8 mug/ml. Two new penicillins, mezlocillin and azlocillin, were similar to ampicillin in their activity. Carbenicillin and ticarcillin inhibited all but a few strains at 128 mug or less/ml. BLP 1654 was somewhat more active than penicillin G against B. fragilis but had similar activity against other anaerobes. Cephalothin was inactive against B. fragilis, and only 65% of other Bacteroides species were inhibited by 32 mug or less/ml. It was effective against all other anaerobes at that level. Cefamandole showed somewhat greater activity than cephalothin against B. fragilis but generally less activity against gram-positive organisms. Cefazaflur (SKF 59962) was comparable to cephalothin against B. fragilis. Cefoxitin was distinctly more active than cephalothin against B. fragilis. These latter two agents were less active than cephalothin against the gram-positive anaerobes. Chloramphenicol remains active against anaerobic bacteria at 16 mug or less/ml, with rare exceptions. Thiamphenicol was similar to chloramphenicol in its activity. Clindamycin was very active against most of the anaerobes at 8 mug or less/ml. Erythromycin and josamycin were also tested, with josamycin showing greater activity against B. fragilis than either erythromycin or clindamycin. A new oligosaccharide, everninomicin B, was less active than clindamycin against B. fragilis but more active against clostridia and some of the other strains tested. Most of the groups of bacteria tested demonstrated a trend toward resistance to tetracycline. Doxycycline and minocycline were somewhat more active than was tetracycline. Metronidazole was active against the majority of the anaerobes tested; resistance ws demonstrated by some of the gram-positive cocci and gram-positive, non-sporeforming bacilli.

Gonococci causing disseminated gonococcal infection are resistant to the bactericidal action of normal human sera.

Abstract: The susceptibility of strains of Neisseria gonorrhoeae to the bactericidal action of normal human sera was determined for isolates from patients with disseminated gonococcal infection and uncomplicated gonorrhea. Serum susceptibility was correlated with penicillin susceptibility and auxotype. 38 of 39 strains (97%) of N. gonorrhoeae from Seattle patients with disseminated gonococcal infection were resistant to the complement-dependent bactericidal action of normal human sera. 36 of these were inhibited by less than or equal to mug/ml of penicillin G and required arginine, hypoxanthine, and uracil for growth on chemically defined medium (Arg-Hyx-Ura- auxotype). 12 of 43 isolates from patients with uncomplicated gonorrhea were also of the Arg-Hyx-Ura-auxotype, inhibited by less than or equal to 0.030 mug/ml of penicillin G, and serum resistant. Of the 31 remaining strains of other auxotypes isolated from patients with uncomplicated gonorrhea, 18 (58.1%) were sensitive to normal human sera in titers ranging from 2 to 2,048. The bactericidal action of normal human sera may prevent the dissemination of serum-sensitive gonococci. However, since only a small proportion of individuals infected by serum-resistant strains develop disseminated gonococcal infection, serum resistance appears to be a necessary but not a sufficient virulence factor for dissemination. Host factors such as menstruation and pharyngeal gonococcal infection may favor the dissemination of serum-resistant strains. Since serum-resistant Arg-Hyx-Ura strains are far more frequently isolated from patients with disseminated gonococcal infection than serum-resistant strains of other auxotypes, Arg-Hyx-Ura-strains may possess other virulence factors in addition to serum resistance.

National gonorrhea therapy monitoring study: in vitro antibiotic susceptibility and its correlation with treatment results.

Abstract: To monitor temporal trends and regional differences in antibiotic susceptibility, we measured the minimum inhibitory concentrations for penicillin G, ampicillin, tetracycline, and spectinomycin of 4405 pre-treatment gonococcal isolates from patients with uncomplicated gonorrhea. As compared to isolates studied in 1970-1971, recent United States isolates appeared equally sensitive to penicillin G and more sensitive to tetracycline. Relatively resistant strains were found throughout the country. We also studied 1974 patients, treated for uncomplicated gonorrhea according to the 1972 regimens recommended by the United States Public Health Service, to determine the relation between pretreatment minimum inhibitory concentrations and treatment results. For patients receiving the procaine penicillin-probenecid and ampicillin-probenecid regimens, minimum inhibitory concentrations to the treatment drugs were significantly higher in patients not cured than in those cured (P less than 0.01 fr penicillin and P less than 0.05 for ampicillin). In contrast, spectinomycin-treatment results appeared to be independent of the isolate's susceptibility to spectinomycin and other antibiotics.

Neurosyphilis and penicillin levels in cerebrospinal fluid.

Abstract: Because neurosyphilis may progress despite therapy with the recommended penicillin regimens, 15 subjects with positive tests for syphilis in the serum and cerebrospinal fluid (CSF) were studied. All of these patients had CSF pleocytosis. Two received penicillin G (5 and 10 million units per day intravenously, respectively) and 13 received benzathine penicillin G, 3.6 million units per week intramuscularly; treatment lasted four weeks. During intravenous and after intramuscular penicillin therapy, a spinal tap was performed on all subjects; later, assays were done. Of two patients who received intravenous penicillin G, one had 0.3 mug/ml and the other had 2.4 mug/ml penicillin in the CSF. Twelve of 13 patients who received benzathine penicillin G had no detectable penicillin in the CSF; one patient had 0.1 mug/ml penicillin in the CSF.

Persistence of Treponema pallidum following penicillin G therapy. Report of two cases.

Abstract: The isolation ofTreponema pallidumfrom cerebrospinal fluid (CSF) obtained from two adult patients, both of whom had normal CSF values except for positive fluorescent treponemal antibody-absorption (FTA-ABS) tests and both of whom had received currently recommended courses of penicillin, raises important considerations in the treatment of neurosyphilis in adults. (JAMA236:2206-2207, 1976)

Drug therapy: The newer cephalosporins.

Abstract: A host of new semisynthetic penicillins, some differing considerably both in antibacterial spectrums and in pharmacologic properties from the prototype (penicillin G), were introduced in the early ...

Bone Concentrations of Antimicrobial Agents After Parenteral Administration

Abstract: Bone concentrations of seven antimicrobial agents were determined after parenteral administration. Antibiotics were administered in large doses at customary intervals for 12 to 20 h before total hip or knee replacement; anticipated levels of each drug were achieved in the serum. Methicillin, carbenicillin, and clindamycin were detected in bone with greatest frequency. Cefazolin and gentamicin were each detected in bone specimens from only one of four patients. Neither penicillin G nor cephalothin was present in bone in sufficient quantity to be measurable. These data suggest that a number of factors, in addition to serum concentration, affect concentration of antimicrobial agents in bone. The clinical significance of the relationship between bone concentrations of antibiotics and therapeutic outcome is not certain.

Altered penicillin-binding components in penicillin-resistant mutants of Bacillus subtilis

Abstract: Penicillin- (cloxacillin-) resistant mutants of Bacillus subtilis were isolated in a stepwise fashion and the five penicillin-binding components (PBCs) in each were examined to determine which of the proteins, if any, corresponds to the penicillin killing site. PBCs II and V were previously eliminated as the likely penicillin targett. In the present work, PBC IV showed no change in sensitivity to cloxacillin in any of the resistant mutants isolated. PBC I did not change until the fifth-step mutant, in which it could not be detected by penicillin binding. Since PBC I did not bind penicillins that are lethal for this mutant, it also cannot be the lethal target. PBC II showed increased resistance to cloxacillin in three discrete steps, i.e., in mutants 1, 4, and 5, accompanied by changes in its electrophoretic mobility. However, the sensitivity of PBC II to penicillin G changed very little. Correspondingly, the cloxacillin-resistant mutants were unaltered in their sensitivity to penicillin G in vivo. Thus, of the five PBCs found in B. subtilis, PBC II is the most likely target for killing by penicillins.

Bacterial interference: effects of oral antibiotics on the normal throat flora and its ability to interfere with group A streptococci.

Abstract: The effects of orally administered penicillin and tetracycline on the composition of the normal throat flora and its interference with the growth of group A streptococci were evaluated by throat culture and an agar overlay technique. Tetracycline caused only a slight, transient quantitative decrease in the composition of the flora and interference activity. Penicillin caused significant quantitative and qualitative decreases in both the composition of the flora and interference activity. The diminution in interference activity persisted up to 3 weeks after therapy. The differences observed between the antibiotic regimens correlated with differences in initial susceptibility of the flora to the antibiotic used and emergence of the resistance during therapy. Results indicated that although effects of antibiotics on the composition of the flora are transient, effects on its ability to interfere with group A streptococci may persist long after therapy is discontinued. It is thus possible that penicillin therapy may enhance susceptibility of certain individuals to subsequent infection with group A streptococci.

Cefamandole: In Vitro and Clinical Pharmacokinetics

Abstract: Cefamandole has a broader spectrum and greater potency than the other cephalosporins. It includes Haemophilus influenzae, most strains of Enterobacter, and many strains of indole-positive Proteus and Bacteroides, with a lower minimal inhibitory concentration for Escherichia coli, Klebsiella, etc. Concentrations of drug in the serum after the parenteral injection of cefamandole exceed manyfold the minimal inhibitory concentrations of over 82% of the bacteria studied. Approximately 65 to 85% is excreted in a biologically active form in the urine. This antibiotic offers advantages of antibacterial effectiveness and at the same time retains the safety of penicillin G and cephalothin in animals.

Inactivation of Gentamicin by Penicillins in Patients with Renal Failure

Abstract: Kinetics of gentamicin inactivation by carbenicillin and ticarcillin were studied in vitro and in 17 patients with renal failure. In vitro, the half-life of carbenicillin in human serum at 37 C is longer (19.2 ± 0.7 h) than ticarcillin (7.2 ± 0.6 h). Thus, incubation of gentamicin with equal concentrations of ticarcillin or carbenicillin results in greater inactivation of aminoglycoside activity by the latter. If concentrations of the two penicillins are held equal by repetitive addition, rates of gentamicin inactivation are the same. The serum half-life of gentamicin in patients serving as their own controls was significantly reduced by administration of either penicillin. After carbenicillin, the half-life decreased from 46 ± 8 h to 22 ± 3 h (P < 0.02). The constant for inactivation of gentamicin (ki) by carbenicillin was 0.02 h−1. The results indicate that gentamicin requirements are underestimated by methods currently employed to calculate dosage for patients with renal failure who receive carbenicillin concurrently. Adjustment of gentamicin dosage in such cases by application of the ki for gentamicin is suggested.

Stable L-forms of Clostridium perfringens and their growth on glass surfaces.

Abstract: L-forms of Clostridium perfringens were induced in brain heart infusion broth containing 10% sucrose and 2 units of penicillin. After a few hours of growth, spheroplasts, granules, and elongated ba...

Prolonged pneumococcal meningitis due to an organism with increased resistance to penicillin.

Abstract: For more than 30 years, penicillin has been the agent of choice for pneumococcal infections. During this time the majority of strains of Streptococcus pneumoniae have been highly susceptible to penicillin. However, during the last ten years there have been sporadic reports of pneumococci with increased resistance to penicillin. The case report of an 18-month-old white boy with meningitis due to a strain of S. pneumoniae with increased resistance to penicillin is presented. The MIC of the organism to penicillin was 0.2 mug/ml and the MBC 0.39 mug/ml. The patient had normal immunity and no demonstrable sequestered focus of infection but failed to respond to appropriate doses of intravenous penicillin. Treatment with chloramphenicol caused a dramatic bacteriologic and clinical response. This experience reemphasizes the existence of pneumococcal strains of intermediate penicillin sensitivity and the importance of in vitro susceptibility tests.

National gonorrhea therapy monitoring study: treatment results.

Abstract: To monitor the efficacy of the 1972 United States Public Health Service recommended treatment regimens for uncomplicated gonorrhea, we studied 9008 patients who were randomly assigned either to aqueous procaine penicillin G, 4.8 million units intramuscularly plus 1 g of oral probenecid, or to one of the three other recommended regimens. Among the 3871 patients re-examined within three to seven days after therapy, the penicillin-probenecid regimen was successful in 96.8 per cent, whereas the cure rates of the ampicillin-probenecid, tetracycline, and spectinomycin regimens were 92.8, 96.2, and 94.8 per cent, respectively. In clinics comparing the regimens, penicillin G-probenecid was as effective as tetracycline, but more effective than ampicillin-probenecid (P less than 0.05) and spectinomycin (P less than 0.01). However, in patients re-examined three to 14 days after treatment, only the ampicillin-probenecid regimen was significantly less effective than penicillin probenecid (P less than 0.01). Despite these differences in results, all four regimens recommended by the Public Health Service provided effective therapy for uncomplicated gonorrhea.

Continuous production of 6-aminopenicillanic acid from penicillin by immobilized microbial cells

Abstract: For continuous production of 6-aminopenicillanic acid (6-APA) the microbial cells ofEscherichia coli ATCC 9637 having high penicillin amidase (penicillin amidohydrolase, E.C. 3. 5. 1. 11) activity were immobilized by entrapment in a polyacrylamide gel lattice. Enzymatic properties of penicillin amidase of the immobilizedE. coli cells were investigated and compared with those of the intact cells. With regard to optimal pH and temperature, no marked difference was observed. The heat stability was somewhat increased by immobilization of the cells. The enzyme activity of the immobilized cell column was stable, and its half-life was 17 days at 40°C and 42 days at 30°C. From the effluent of the column, 6-APA was easily obtained in a good yield.

Clinical patterns and results of radioallergosorbent test (RAST) and skin tests in penicillin allergy

Abstract: SUMMARY Seventy-nine patients with acute or former reactions to penicillin were investigated by a benzyl-penicilloyl (BPO)-specific RAST and/or by skin tests with penicilloyl-polylysine (PPL), benzyl-penicillin and penicilloic acid and the results were correlated with the different clinical pictures. Positive RAST and skin test results could be found in patients with anaphylactic shock, urticaria and serum sickness-like reaction and sometimes in a special group of exanthems, which are characterized by the existence of many different lesions at the same time, therefore called ‘polymorphic exanthems’, and often observed after high-dosage penicillin therapy. In cases of scarlatiniform or morbilliform exanthems no positive results were found. The BPO-specific RAST showed an overall correlation of 95·1% with skin tests using PPL. However, some patients with positive skin tests to benzylpenicillin and penicilloic acid did not have detectable circulating IgE antibodies to BPO. This emphasizes the need for including these antigens in in vitro methods. The RAST was informative even at the time of the allergic reaction or in the first 15 days afterwards and seems to be very valuable for early diagnosis of penicillin allergy especially in cases when many drugs have been given.

Characteristics of atypical Neisseria gonorrhoeae from disseminated and localized infections.

Abstract: Approximately 6% of 1,200 clinical isolates of Neisseria gonorrhoeae were atypical because they produced smaller than normal colonies on conventioal chocolate agar and fermented glucose weakly. Auxotyping studies indicated that these atypical strains required for growth arginine, uracil, and, in most instances, hypoxanthine. In addition, all of them were susceptible to 0.02 U of penicillin/ml. None of the normal colony isolates, including those susceptible to the same low concentration of penicillin, had the same nutritional characteristics. Atypical strains comprised almost half of the isolates from disseminated infections, but only 5% of those from localized infections. Auxotyping was used to identify the contact of a patient who became reinfected nine times with an atypical gonoccal strain. In addition to its usefulness in such epidemiological studies, this technique has enabled us to distinguish a subgroup of gonococci with apparent increased pathogenicity. Images