Showing papers on "Penicillin published in 1985"
TL;DR: It is suggested that MRSA strains can grow in the presence of beta-lactam antibiotics because of the low affinities of the specific PBP2' fraction for various beta-biotic antibiotics.
Abstract: About 80% of methicillin- and cefazolin-resistant strains of Staphylococcus aureus isolated clinically in Japan in 1982 retained their resistance even after elimination of penicillinase-encoding plasmids. The penicillin-binding proteins (PBPs) of the penicillinase-free, methicillin- and cephem-resistant subclones of Staphylococcus aureus (MRSA) were compared with those of spontaneous susceptible revertants which had been obtained by the replica method after 10 subcultures in drug-free media. A new PBP fraction (PBP2') having a molecular weight of 78,000 and low binding affinities for various beta-lactam antibiotics was found in MRSA exclusively. The levels of resistance of MRSA strains were reduced markedly by culturing them at 43 degrees C or at pH 5.2 or both. We found that the binding capacity of PBP2' for 14C-labeled penicillin G was decreased by preincubation of the membrane fractions of MRSA strains at 43 degrees C for 60 min and that the amount of PBP2' in MRSA strains grown at pH 5.2 was less than that the amount of PBP2' in MRSA strains grown at pH 7.0. Temperature- and pH-dependent expression of resistance in MRSA is likely to reflect the temperature sensitivity and neutral pH-dependent production of the specific PBP fraction (PBP2'). We suggest that MRSA strains can grow in the presence of beta-lactam antibiotics because of the low affinities of the specific PBP2' fraction for various beta-lactam antibiotics.
350 citations
TL;DR: It is concluded that established Lyme arthritis can often be treated successfully with parenteral penicillin, however, neither of the regimens that are tested is uniformly effective, and further experience will be needed to determine the optimal course of therapy.
Abstract: In a double-blind placebo-controlled trial carried out from 1980 to 1982, 20 patients with established Lyme arthritis were assigned treatment with 2.4 million U of intramuscular benzathine penicillin weekly for three weeks (total, 7.2 million U) and 20 patients received saline. Seven of the 20 penicillin-treated patients (35 per cent) had complete resolution of arthritis soon after the injections and have remained well during a mean follow-up period of 33 months. In contrast, all 20 patients given placebo continued to have attacks of arthritis (P<0.02). In 1983, of 20 patients treated with intravenous penicillin G, 20 million U a day for 10 days, 11 (55 per cent) had complete resolution of arthritis and have remained well since. As compared with nonresponders, penicillin-responsive patients in both studies were more likely to have previously received antibiotics for erythema chronicum migrans (P<0.02) and less likely to have been given intraarticular corticosteroids during or at the conclusion of...
228 citations
TL;DR: The results indicate that oral desensitization is an acceptably safe approach to therapy in pregnant women who are allergic to penicillin and have infections that require beta-lactam drugs.
Abstract: Penicillin allergy presents a major obstacle to the successful management of some antepartum infections. We studied 15 pregnant women with histories of penicillin allergy confirmed by positive immediate wheal-and-flare skin tests. Thirteen had syphilis, one listeria sepsis, and one Streptococcus viridans endocarditis. Each patient was desensitized over four to six hours by oral administration of increasing doses of penicillin V. At the completion of the procedure, full-dose parenteral therapy with penicillin G or ampicillin was instituted. No extracutaneous reactions were detected. Five of the subjects (33 per cent) experienced pruritus (three) or urticaria (two), but no interruption of desensitization or therapy was necessary. All clinically apparent maternal infections were cured. The pregnancy complicated by listeriosis aborted in the first trimester. The 11 neonates delivered to date are normal. These results indicate that oral desensitization is an acceptably safe approach to therapy in pregnant women who are allergic to penicillin and have infections that require beta-lactam drugs.
199 citations
TL;DR: It is concluded that early penicillin treatment of children with streptococcal pharyngitis significantly alters the acute clinical course of the disease.
Abstract: Forty-four children with a clinical diagnosis of streptococcal pharyngitis had throat cultures performed at the initial evaluation and were assigned by randomization to receive either oral penicillin or a placebo for 72 hours. The treating physician, who remained blind to the treatment regimen, recorded the child's temperature and assessed the presence and severity of other signs and symptoms initially and at 24, 48, and 72 hours. The throat culture was positive for group A beta-hemolytic streptococci in 26 (59%) of the initial study group, and most of these children developed a fourfold or greater titer rise in antistreptococcal antibodies in their serum, confirming the diagnosis of streptococcal pharyngitis. Statistically significant clinical improvement was observed in the group of 11 children who were later shown to have been taking penicillin compared with the group of 15 who had taken the placebo. Significant differences in the presence and degree of fever and severity of symptoms persisted in the placebo-treated group for 48 hours. We conclude that early penicillin treatment of children with streptococcal pharyngitis significantly alters the acute clinical course of the disease.
183 citations
TL;DR: Significantly fewer children who had received either penicillin or cefadroxil had persistence of each of the three objective signs and each ofThe three subjective symptoms in GABHS pharyngitis than did children who received placebo.
179 citations
TL;DR: There was a good correlation between the inhibitory capacity of 3-lactam antibiotics in vitro and the doses inducing neutropenia in vivo and these observations may be relevant for therapy in the granulocytopenic patient.
Abstract: beta-Lactam antibiotics can induce severe neutropenia by a hitherto unknown mechanism. Fifty cases of beta-lactam antibiotic-induced neutropenia (less than 1,000 neutrophils/mm3) from 17 hospitals were analyzed and compared with 140 literature cases. The incidence of neutropenia was 5%-greater than 15% in patients treated for greater than or equal to 10 days with large doses of any beta-lactam antibiotic but less than 0.1% with shorter duration of therapy. In greater than 95% of cases recovery occurred between one to seven days after withdrawal of beta-lactam antibiotics. Bone marrow aspirates were characterized by a lack of well-differentiated myeloid elements in the presence of numerous immature granulocyte precursors. Nine penicillins and eight cephalosporins inhibited in vitro granulopoiesis in a dose-dependent manner. There was a good correlation between the inhibitory capacity of beta-lactam antibiotics in vitro and the doses inducing neutropenia in vivo. These observations may be relevant for therapy in the granulocytopenic patient.
166 citations
TL;DR: Results establish the value of antimicrobial treatment in the management of tetanus and show that metronidazole is more efficacious than penicillin in this respect.
Abstract: A prospective, open, non-randomised clinical trial was carried out to compare the efficacy of procaine penicillin with metronidazole in the treatment of moderate tetanus among 173 patients. Patients in the metronidazole group had a significantly lower mortality rate, a shorter stay in hospital, and an improved response to treatment. These results establish the value of antimicrobial treatment in the management of tetanus and show that metronidazole is more efficacious than penicillin in this respect.
158 citations
TL;DR: It is suggested thatPenicillin tolerance may be responsible for some instances of failure of penicillin to eradicate group A streptococci from the upper respiratory tract of individuals with Streptococcal tonsillitis or pharyngitis.
132 citations
TL;DR: It is suggested that the strictly anaerobic bacterial populations which predominate in the gut ecosystem are responsible for the inhibition of C. albicans adhesion, colonization and dissemination from the GI tract.
Abstract: Mice were treated orally with various antibiotics to determine which members of the indigenous intestinal microflora normally suppress Candida albicans colonization and dissemination from the gastrointestinal (GI) tract. The mice were given penicillin, clindamycin, vancomycin, erythromycin, or gentamicin for 3 days, and then challenged orally with C. albicans. Penicillin, clindamycin, and vancomycin, but not gentamicin or erythromycin, decreased the total anaerobic bacterial populations in the animals ceca, and increased the enteric bacilli population levels. All three of the former antibiotics allowed C. albicans to proliferate in the gut and, subsequently, disseminate from the GI tract to visceral organs. The ability of C. albicans to associate with intestinal mucosal surfaces was also tested. It was found that antibiotics which reduced anaerobic population levels, but not enteric bacilli or aerobes, also predisposed animals to mucosal association by C. albicans. It is suggested that the strictly anaerobic bacterial populations which predominate in the gut ecosystem are responsible for the inhibition of C. albicans adhesion, colonization and dissemination from the GI tract.
125 citations
TL;DR: The outbreak was halted by changing the treatment for all patients and their contacts to spectinomycin, and by intensive epidemiologic case-finding efforts, and indicates a need for reassessment of current surveillance procedures.
Abstract: From February through November of 1983, 199 cases of penicillin-resistant Neisseria gonorrhoeae infection were identified in a localized epidemic in Durham, North Carolina. The isolates did not produce beta-lactamase but were unusually resistant to penicillin (minimum inhibitory concentration, 2.0 to 4.0 μg per milliliter), and 15 of 16 patients treated with 4.8 million units of penicillin G procaine plus 1.0 g of probenecid did not respond to therapy. Recognition of the outbreak was impeded by a lack of routine surveillance for resistance other than that mediated by beta-lactamase. All epidemic isolates had a single serotype, auxotype, and antibiotic-susceptibility profile. The outbreak was halted by changing the treatment for all patients and their contacts to spectinomycin, and by intensive epidemiologic case-finding efforts. The emergence of such resistant strains poses potential major public health problems and indicates a need for reassessment of current surveillance procedures. (N Engl J Med 1985; ...
124 citations
TL;DR: No single antibiotic, at concentrations equivalent to those achieved in body fluids, was uniformly effective in inhibiting all bacteria currently implicated or suspected as etiologic agents of periodontal diseases.
Abstract: In vitro susceptibilities of 369 to 966 bacterial isolates from periodontal lesions to eight antibiotics were determined by agar dilution technique as a means of determining which antimicrobial agents were inhibitory for bacteria frequently associated with destructive periodontal diseases. Although most bacteria were relatively susceptible to the penicillins, greater activity was generally noted with amoxicillin than with either penicillin or ampicillin with the exception of Selenomonas sputigena and Peptostreptococcus. Antibacterial activities obtained with minocycline were significantly higher than with tetracycline for Actinobacillus actinomycetemcomitans and Streptococcus but comparable for most other taxa. Clindamycin and metronidazole both demonstrated excellent activity against the anaerobic Gram-negative rods but were less effective against some of the capnophilic and facultative organisms. Eikenella corrodens was exceptionally resistant to both of these drugs; and A. actinomycetemcomitans was gen...
TL;DR: A strain of heterogeneously methicillin-resistant Staphylococcus aureus produced an extra 78-kD PBP that had a low affinity for nafcillin and penicillin, which suggests that the synthesis of PBP 2a can be stimulated by exposure to beta-lactam antibiotics.
Abstract: In addition to the four typical penicillin-binding proteins (PBPs), a strain of heterogeneously methicillin-resistant Staphylococcus aureus produced an extra 78-kD PBP (PBP 2a) that had a low affinity for nafcillin and penicillin. Addition of nafcillin to cultures of this strain caused a rapid increase in the amount of this PBP in cell membranes. This increase occurred at subinhibitory concentrations of drug within minutes of exposure, and was blocked by inhibitors of protein and RNA synthesis. This suggests that the synthesis of PBP 2a can be stimulated by exposure to beta-lactam antibiotics. This process may, in part, explain the heterogeneity in methicillin-resistant S. aureus.
TL;DR: Five of six multiply drug-resistant clinical isolates of Streptococcus pneumoniae from South Africa demonstrated penicillin tolerance, suggesting that the drug-specific tolerance of the South African pneumococcal strains is related to some alteration in the control of autolysin activity.
Abstract: Five of six multiply drug-resistant clinical isolates of Streptococcus pneumoniae from South Africa demonstrated penicillin tolerance. In contrast to the common wild-type strains of pneumococci, treatment of the tolerant strains with penicillin above the minimum inhibitory concentration did not induce cell wall degradation, lysis, or leakage of intracellular components, and the rate of loss of viability was reduced compared with that of nontolerant strains. While these South African strains contained lower specific activity of autolytic enzyme than did nontolerant strains, the residual autolytic activity (15%-26% of the nontolerant wild type) was much more than that found in lysis-defective laboratory mutants of pneumococci (less than or equal to 1%); the rate of penicillin-induced lysis did not correlate with the specific activity of residual autolysin. Also, in contrast to the complete lysis resistance of lysis-defective mutants to all lytic agents, the tolerant South African strains were resistant primarily to lysis by beta-lactam antibiotics but could still be lysed by other cell wall inhibitors (e.g., cycloserine) and detergents. The penicillin resistance and penicillin tolerance traits could be separated by genetic transformation. We suggest that the drug-specific tolerance of the South African pneumococcal strains is related to some alteration in the control of autolysin activity.
TL;DR: This finding suggested that Rev 14 hypersusceptibility was due to the lack of PBP 5 and strongly supported the role of this protein in the mechanism of both natural low susceptibility and high-level resistance to beta-lactams in S. faecium.
Abstract: Penicillin-binding protein (PBP) 5 of Streptococcus faecium has been shown to have a very low affinity for penicillin, and this PBP was suggested to be responsible for both the natural low susceptibility and high resistance to the antibiotic in this species (R. Fontana, R. Cerini, P. Longoni, A. Grossato, and P. Canepari, J. Bacteriol. 155:1343-1350, 1983). In this study, an S. faecium mutant (Rev 14) hypersusceptible to penicillin was derived from the highly resistant S. faecium R40 treated with novobiocin, and its properties were compared with those of the parent and S. faecium PS, a relatively susceptible strain from which R40 was isolated. The hypersusceptible strain did not synthesize PBP 5, but it did resemble the parent in cell morphology, growth rate, and autolytic activity. In addition, it was highly susceptible to other beta-lactams but remained as susceptible as R40 and PS to antibiotics of a different mechanisms of action. The affinity of individual PBPs for the beta-lactams tested was the same in all the strains. This finding suggested that Rev 14 hypersusceptibility was due to the lack of PBP 5 and strongly supported the role of this protein in the mechanism of both natural low susceptibility and high-level resistance to beta-lactams in S. faecium.
TL;DR: Rifampin plus benzathine penicillin intramuscularly is an effective regimen for those selected patients in whom eradication of group A streptococcal carriage is judged to be desirable.
TL;DR: An association between failure to eradicate Group A beta-hemolytic streptococci and the presence of aerobic and anaerobic BLPO is demonstrated.
TL;DR: Patients with a history of recurrent tonsillitis associated with Group A beta- hemolytic streptococcal infection participated in a prospective, randomized study comparing penicillin, erythromycin, or clindamycin therapy, and found that GABHS colonization was eradicated in two of 15 patients treated withPenicillin.
Abstract: Forty-five patients with a history of recurrent tonsillitis associated with Group A beta-hemolytic streptococcal (GABHS) infection participated in a prospective, randomized study comparing penicillin, erythromycin, or clindamycin therapy. Surface tonsillar cultures were obtained before therapy, 10 days after termination of therapy, and once a month for a period of 12 to 18 months. The specimens were processed for aerobic and anaerobic bacteria. Beta lactamase-producing aerobic and anaerobic bacteria were present in 43 of the 45 (96%) tonsillar cultures. GABHS colonization was eradicated in two of 15 patients treated with penicillin, in six of 15 treated with erythromycin, and in 14 of the 15 treated with clindamycin. In long-term follow-up, 12 of 14 patients treated with penicillin, eight of 14 treated with erythromycin, and one of 15 treated with clindamycin (p less than 0.0001 when compared to penicillin and p = 0.002 when compared to erythromycin) continued to suffer from recurrent tonsillitis.
TL;DR: Anaerobic, agar-dilution, minimal inhibitory concentrations (MICs) of 18 antibiotics are given for the numerically important bacterial groups from the human oral cavity, and strains are divided into susceptibility categories using the guidelines for interpretation of MICs suggested by the National Committee for Clinical Laboratory Standards.
Abstract: Anaerobic, agar-dilution, minimal inhibitory concentrations (MICs) of 18 antibiotics are given for the numerically important bacterial groups from the human oral cavity. Strains are divided into susceptibility categories using the guidelines for interpretation of MICs suggested by the National Committee for Clinical Laboratory Standards. These guidelines are based on data on antibiotic concentrations attainable in serum following various dosage regimens. MICs are also compared with attainable gingival fluid levels where these are known. The highest percentages of strains were susceptible to tetracycline, with 89% of the 139 strains tested susceptible to serum levels and 97% conditionally susceptible to attainable gingival fluid levels. Ninety-eight percent of strains were conditionally susceptible to attainable gingival fluid levels of minocycline, but many strains, including Actinobacillus actinomycetemcomitans, were only moderately susceptible to attainable serum levels of this tetracycline analogue. Carbenicillin was effective against most groups of organisms, with the important exception of A. actinomycetemcomitans, at serum levels attainable with oral formulations of carbenicillin. Only 2% of the total strains tested were resistant to penicillin, while 33% of strains were categorized as moderately susceptible. Clindamycin was active against many strains of Gram-negative bacteria but was not active against A. actinomycetemcomitans, some Bacteroides, Eikenella corrodens, or the anaerobic vibrios. Metronidazole was active against A. actinomycetemcomitans, all five groups of oral Bacteroides tested, and against Capnocytophaga species. Chloramphenicol was active against A. actinomycetemcomitans, but not against most of the other groups of oral organisms. Nearly all groups contained strains non-susceptible to serum levels attainable with the usual doses of erythromycin, spiramycin, vancomycin, kanamycin, neomycin, streptomycin, doxycycline, oxytetracycline, or chlortetracycline; several strains were resistant to maximum attainable serum levels of each of these antibiotics except doxycycline.
Dissertation•
01 Jan 1985
TL;DR: It is concluded that in the benzylpenicilloyl group at least three epitopes can be recognized and that Pen 9 mainly recognizes the thiazolidine ring of penicillin.
Abstract: Three monoclonal antibodies (Pen 4, Pen 7 and Pen 9) were raised against the benzylpenicilloyl group and used to investigate the antigenicity of this group. The binding of Pen 4 to carrier-bound penicillin derivatives was shown in an ELISA to be dependent on the structure of the side chain in the derivative. Hence Pen 4 recognizes this side chain. From the difference in binding to carrier-bound penicillin derivatives in a competitive enzyme immunoassay it was concluded that Pen 7 mainly recognizes the new antigenic determinant which emerges from the binding of the penicillin derivative to a carrier. The binding of Pen 9 to carrier-bound penicillin derivatives was not influenced by the nature of the side chain. Neither was the bound or free nature of the derivative of influence on the binding. Therefore it is concluded that Pen 9 mainly recognizes the thiazolidine ring of penicillin. This study thus shows that in the benzylpenicilloyl group at least three epitopes can be recognized.
TL;DR: The high incidence of resistance to multiple antibiotics clearly indicates the need to perform antibiotic susceptibility testing of all pneumococcal isolates with proved pathologic significance to avoid therapeutic failure.
Abstract: A total of 100 Streptococcus pneumoniae strains with various penicillin G susceptibilities, isolated in Barcelona, Spain, from different pediatric sources during 1983 and the first 4 months of 1984, were tested for susceptibility to tetracycline, chloramphenicol, erythromycin, clindamycin, vancomycin, and rifampin. The isolates were distributed in nine patterns of antibiotic resistance, and 15 different serotypes were encountered. The high incidence of resistance to multiple antibiotics clearly indicates the need to perform antibiotic susceptibility testing of all pneumococcal isolates with proved pathologic significance to avoid therapeutic failure.
TL;DR: Results show that addition of rifampin to the penicillin regimen improves the clinical and bacteriologic cure rates in children with streptococcal pharyngitis.
TL;DR: The immunochemistry of aztreonam, the prototype of the new monobactam class of beta-lactam antibiotics, was studied in a series of experimental and clinical investigations and suggests that it may be well tolerated by penicillin-allergic individuals.
Abstract: The immunochemistry of aztreonam, the prototype of the new monobactam class of beta-lactam antibiotics, was studied in a series of experimental and clinical investigations. Rabbit antibodies to aztreonam and naturally occurring human antibodies that recognize aztreonam were found to have negligible cross-reactivity with benzylpenicillin, cephalothin, and cefotaxime. Aztreonam likewise displayed negligible cross-reactivity (less than or equal to 0.001%) with antibodies to penicillin (including human IgE antibodies to major and minor penicillin determinants) and to cephalothin. These studies suggest that aztreonam may be well tolerated by penicillin-allergic individuals, and this possibly is now being evaluated in clinical trials. Seven (6.25%) of 112 healthy persons tested had preexisting IgG antibodies to aztreonam in low titer, presumably as a result of exposure to naturally occurring cross-reacting moieties. Only two of seven patients with preexisting IgG antibodies to aztreonam had a rise in titer following aztreonam treatment. No IgE antibody to aztreonam was detected in serum specimens obtained on day 10 during any of the 112 courses of therapy. These clinical observations suggest but do not prove that aztreonam has only weak potential to elicit a drug-specific immunologic response.
TL;DR: Ceftriaxone may prove to be a drug of choice for uncomplicated gonorrhea, particularly where homosexual men are treated and/or penicillinase-producing N gonorrhoeae is prevalent.
Abstract: Of the currently recommended regimens for treatment of uncomplicated gonorrhea, only aqueous penicillin G procaine is effective against infections at all sites. However, procaine penicillin is not effective against penicillinase-producingNeisseria gonorrhoeaeand suffers from poor patient acceptability owing to the 10-mL volume of injection and allergic and toxic procaine reactions. Ceftriaxone is a new extended-spectrum cephalosporin with a long serum half-life and is many times more active than penicillin G against both β-lactamase—positive or —negative strains ofN gonorrhoeae. Ceftriaxone was compared as a single, 125-mg, 0.5-mL injection with a single 2-g injection of spectinomycin in difficult to treat pharyngeal gonorrhea in men and women and anorectal gonorrhea of men. Ceftriaxone cured 30/32 (94%) pharyngeal and 52/52 anorectal infections, compared with 6/14 (43%) and 9/9, respectively, for spectinomycin. Both regimens were well tolerated. Ceftriaxone may prove to be a drug of choice for uncomplicated gonorrhea, particularly where homosexual men are treated and/or penicillinase-producingN gonorrhoeaeis prevalent. (JAMA1985;253:1417-1419)
TL;DR: It is suggested that penicillin V given twice daily is as effective as penichill V given three times daily for the treatment of GABHS pharyngitis.
Abstract: • An investigation was performed to compare the effectiveness of oral penicillin V given twice daily with penicillin V given three times daily in the treatment of group A βhemolytic streptococcal (GABHS) pharyngitis. Patients were randomly assigned to receive 250 mg of penicillin V either two or three times daily for ten days. Overall, 23 (23%) of 99 patients had the same strain of GABHS isolated from their follow-up as from their initial throat culture and were considered to have bacteriologic-treatment failures. Of the 50 patients in the three-times-daily group, nine (18%) had bacteriologic-treatment failures, while 14 (28.5%) of 49 patients in the twice-daily group had bacteriologic-treatment failures. The results of this and earlier investigations suggest that penicillin V given twice daily is as effective as penicillin V given three times daily for the treatment of GABHS pharyngitis. ( AJDC 1985;139:1145-1148)
TL;DR: Despite the "poor" permeation of gentamicin into the CSF, the accelerated killing of streptococci at low concentrations of this antibiotic provides a rationale for the initial use of a combination of penicillin or ampicillin and Gentamicin in the treatment of group B strePTococcal meningitis.
Abstract: Antimicrobial sensitivity, synergy, and timed-killing assays were determined for 20 strains of group B streptococci isolated from cultures of blood and cerebrospinal fluid (CSF) of infected neonates. The mean minimal inhibitory concentrations by the tube-dilution method were as follows: penicillin, 0.02 microgram/ml; ampicillin, 0.05 microgram/ml; and gentamicin, 4.5 micrograms/ml. No synergy was detected with any combination of penicillin or ampicillin and gentamicin by the checkerboard titration method. Killing kinetics were determined for combinations of penicillin or ampicillin and gentamicin at low concentrations of these antibiotics comparable to those attained in the CSF following systemic administration of these antibiotics. Addition of 0.1 microgram and 0.5 microgram of gentamicin/ml to penicillin or ampicillin significantly accelerated the killing of group B streptococci. Despite the "poor" permeation of gentamicin into the CSF, the accelerated killing of streptococci at low concentrations of this antibiotic provides a rationale for the initial use of a combination of penicillin or ampicillin and gentamicin in the treatment of group B streptococcal meningitis.
TL;DR: The pharmacokinetics and bacteriological efficacies of penicillin G, ceftriaxone, vancomycin, and imipenem were determined in rabbits with experimental meningitis caused by Streptococcus pneumoniae strains with differentPenicillin susceptibilities to achieve a maximal bacteriological effect.
Abstract: The pharmacokinetics and bacteriological efficacies of penicillin G, ceftriaxone, vancomycin, and imipenem were determined in rabbits with experimental meningitis caused by Streptococcus pneumoniae strains with different penicillin susceptibilities. Drug dosages were adjusted to attain peak concentrations in serum that were similar to those observed in infants and children. In animals infected with a penicillin-susceptible (MBC, 0.008 micrograms/ml) pneumococcus, penicillin G and ceftriaxone reduced the number of organisms in cerebrospinal fluid (CSF) by greater than or equal to 4.14 log10 CFU/ml after single doses and after 9-h continuous infusions. A single large dose (50 mg/kg) of penicillin G was comparatively ineffective (-2.15 log10 CFU/ml) against a relatively penicillin-resistant (MBC, 0.5 micrograms/ml) strain, whereas ceftriaxone therapy resulted in a 3.66- and 4.77-log10 CFU/ml reduction after single doses and 9-h continuous infusions, respectively. In animals in which meningitis was caused by a penicillin-resistant (MBC, 8.0 micrograms/ml) pneumococcus, a single dose of penicillin (50 or 150 mg/kg) or of ceftriaxone failed to lower the number of organisms in CSF. Vancomycin and imipenem reduced the counts in CSF by at least 2.19 and 4.10 log10 CFU/ml after single doses and 9-h infusions, respectively. In all experiments, a bactericidal titer of greater than or equal to 1:8 in CSF was necessary to achieve a maximal bacteriological effect.
TL;DR: Penicillin G acylase from Proteus rettgeri is an 80-000- to 90,000-dalton enzyme composed of two nonidentical subunits that imparts specificity for the penicillin side chain.
Abstract: Penicillin G acylase from Proteus rettgeri is an 80,000- to 90,000-dalton enzyme composed of two nonidentical subunits. Both subunits were required for enzymatic activity. The 65,000-dalton beta subunit contained a phenylmethylsulfonyl fluoride-sensitive residue required for enzymatic activity, and the 24,500-dalton alpha subunit contained the domain that imparts specificity for the penicillin side chain.
TL;DR: The cross-reactivity between the monobactam antibiotic aztreonam and the commonly used beta-lactam antibiotics, penicillins, and cephalosporins was investigated and results indicate that there is very little cross- reactivity.
TL;DR: Patients with infective endocarditis caused by penicillin-sensitive streptococci that have had symptoms for longer than three months or perhaps patients with mitral valve infection should receive at least six weeks ofPenicillin therapy together with an aminoglycoside; patients without either high-risk factor may be treated successfully for four weeks.