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Showing papers on "Penicillin published in 1995"


Journal ArticleDOI
TL;DR: Current levels of resistance to penicillin and cephalosporin by S. pneumoniae are not associated with increased mortality in patients with pneumococcal pneumonia, and these antibiotics remain the therapy of choice for this disease.
Abstract: Background Penicillin-resistant strains of Streptococcus pneumoniae are now found worldwide, and strains with resistance to cephalosporin are being reported. The appropriate antibiotic therapy for pneumococcal pneumonia due to resistant strains remains controversial. Methods To examine the effect of resistance to penicillin and cephalosporin on mortality, we conducted a 10-year, prospective study in Barcelona of 504 adults with culture-proved pneumococcal pneumonia. Results Among the 504 patients, 145 (29 percent) had penicillin-resistant strains of S. pneumoniae (minimal inhibitory concentration [MIC] of penicillin G, 0.12 to 4.0 μg per milliliter), and 31 patients (6 percent) had cephalosporin-resistant strains (MIC of ceftriaxone or cefotaxime, 1.0 to 4.0 μg per milliliter). Mortality was 38 percent in patients with penicillin-resistant strains, as compared with 24 percent in patients with penicillin-sensitive strains (P = 0.001). However, after the exclusion of patients with polymicrobial pneumonia an...

765 citations


Journal ArticleDOI
TL;DR: Penicillin is again the agent of choice for secondary prophylaxis, but sulfadiazine or erythromycin are acceptable alternatives in penicillin-allergic individuals.
Abstract: Primary prevention of acute rheumatic fever is accomplished by proper identification and adequate antibiotic treatment of group A beta-hemolytic streptococcal (GAS) tonsillopharyngitis. Diagnosis of GAS pharyngitis is best accomplished by a throat culture. Penicillin (either oral penicillin V or injectable benzathine penicillin) remains the treatment of choice, because it is cost effective, has a narrow spectrum of activity, has long-standing proven efficacy, and GAS resistant to penicillin have not been documented. Various macrolides, oral cephalosporins, and other beta-lactam agents are acceptable alternatives, particularly in penicillin-allergic individuals. The individual who has had an attack of rheumatic fever is at very high risk of developing recurrences after subsequent GAS pharyngitis and needs continuous antimicrobial prophylaxis to prevent such recurrences (secondary prevention). The duration of prophylaxis depends on the number of previous attacks, the time lapsed since the last attack, the risk of exposure to streptococcal infections, the age of the patient, and the presence or absence of cardiac involvement. Penicillin is again the agent of choice for secondary prophylaxis, but sulfadiazine or erythromycin are acceptable alternatives in penicillin-allergic individuals. This report is an update of a 1988 statement by this committee. It expands on the previous statement, includes more recent therapeutic modalities, and makes more specific recommendations for the duration of secondary prophylaxis.

367 citations


Journal ArticleDOI
TL;DR: It is suggested that intermediate penicillin resistance is of little significance in pneumococcal pneumonia or sepsis and that standard beta-lactam therapy is still highly effective.
Abstract: The continued spread of penicillin-resistant pneumococci raises therapeutic concerns. Optimal therapy for resistant infections is unknown and it is not clear whether the efficacy of penicillin or equally active beta-lactam agents is compromised in non-meningeal-resistant infections. A prospective nonintervention study was undertaken to compare the clinical response in penicillin-resistant vs. penicillin-susceptible bacteremic pneumococcal infections, excluding meningitis. Of 108 children enrolled, 35 (32%) had penicillin-resistant (one highly resistant) isolates. Seventy-eight children had pneumonia, 21 had occult bacteremia (sepsis) and 9 had peritonitis. Children with resistant infections were more likely to have underlying disorders, especially human immunodeficiency virus infection, and to have received antimicrobial therapy in the previous month. After 48 hours of therapy 64% of penicillin-susceptible infections showed improvement vs. 60% of penicillin-resistant infections (odds ratio, 1.2; 95% confidence intervals, 0.5 to 3.0). In children with pneumonia treated with ampicillin or an equivalent beta-lactam agent, 93% with penicillin-susceptible infections had improved by Day 7 of therapy compared with 88% with resistant infections (odds ratio, 1.9; 95% confidence interval 0.3 to 15.9). The durations of respiratory distress, fever and oxygen requirement were similar in penicillin-susceptible and -resistant infections. These results suggest that intermediate penicillin resistance is of little significance in pneumococcal pneumonia or sepsis and that standard beta-lactam therapy is still highly effective. Further studies of highly penicillin-resistant infections are necessary.

200 citations


Journal Article
TL;DR: Data indicate that it is safe to administer cephalosporin antibiotics to penicillin-allergic patients andPenicillin skin tests do not identify potential reactors, and post-marketing studies of second and third generation cep Halosporins showed no increase in allergic reactions in patients with penicillillin allergy histories.
Abstract: Objectives: The purpose of tits review was to analyze available relevant data regarding the safety of administering cephalosporins to penicillin-allergic patients, including the significance of penicillin skin test reactions and any difference related to first, second, or third generation cephalosporins. Background: Penicillin and cephalosporins both contain a beta-lactam ring. This structural similarity has led to considerable confusion about the cross-allergenicity of these drugs and the risk of allergic reactions from cephalosporins in penicillin-allergic patients. Methods: Published reports and post-marketing data from pharmaceutical corporations provided the basis for this analysis. Results: The overall incidence of adverse reactions from cephalosporins ranges from 1% to 10%, with rare anaphylaxis (<0.02%). In patients with histories of penicillin allergy the incidence of cephalosporin reactions is minimally, if at all increased. Post-marketing studies of second and third generation cephalosporins showed no increase in allergic reactions in patients with penicillin allergy histories. Penicillin skin tests do not predict the likelihood of allergic reactions to cephalosporins in patients with histories of perucillin allergy. One reaction occurred in 98 patients (1%) with positive penicillin skin tests and six reactions occurred in 310 patients (2%) with negative tests. Conclusions: These data indicate that it is safe to administer cephalosporin antibiotics to penicillin-allergic patients and penicillin skin tests do not identify potential reactors

197 citations


Journal Article
TL;DR: Different modes of presentation, which elicit a variety of immunological reactivities, may explain the great heterogeneity of the clinical pictures seen in penicillin allergy.
Abstract: To investigate the role of T cells in drug allergy, we stimulated PBMC from penicillin-allergic patients with reactive penicillin G itself or penicillin G coupled with human serum albumin (BPO-HSA). T cell clones specific for penicillin G or BPO-HSA were established and their phenotype and reactivity to both forms of the beta-lactam were analyzed. T cell clones stimulated by penicillin G were CD4 and CD8 positive, whereas BPO-HSA stimulated the growth of CD4+ T cells. The penicillin G-specific clones were HLA class I or class II restricted and processing was not required as fixed APC could still present penicillin G. In contrast, BPO-HSA has to undergo processing to stimulate BPO-HSA-specific T cell clones. In addition to classical APC, activated MHC class II expressing T cells could also restimulate the penicillin G-specific clones, indicating that various cell types might serve as APC. Penicillin G and BPO-HSA-specific T cell clones produced a heterogeneous cytokine pattern as most clones produced high amounts of IL-2, IFN-gamma, TFN-alpha, and rather variable levels of IL-4 and IL-5. Since no Ag processing was required, penicillin G may stimulate T cells by binding directly to MHC molecules on the cell surface or to their embedded peptide. Alternatively, it may bind to soluble proteins like HSA, which are processed and subsequently presented in an immunogenic form. These different modes of presentation, which elicit a variety of immunological reactivities, may explain the great heterogeneity of the clinical pictures seen in penicillin allergy.

193 citations


Journal ArticleDOI
TL;DR: Children with sickle cell anemia who have not had a prior severe pneumococcal infection or a splenectomy and are receiving comprehensive care may safely stop prophylactic penicillin therapy at 5 years of age.

176 citations


Journal ArticleDOI
TL;DR: Two strains of Streptococcus pneumoniae CS109 and CS111 were isolated in the United States in 1991 and have high levels of resistance to expanded-spectrum cephalosporins (MICs of 8 and 32 micrograms of cefotaxime per ml, respectively), but CS109, but not CS111, also showed high-level resistance to penicillin.
Abstract: Streptococcus pneumoniae CS109 and CS111 were isolated in the United States in 1991 and have high levels of resistance to expanded-spectrum cephalosporins (MICs of 8 and 32 micrograms of cefotaxime per ml, respectively). CS109, but not CS111, also showed high-level resistance to penicillin. As both strains expressed the serotype 23F capsule, were very closely related in overall genotype, and possessed identical or closely related mosaic pbp1a, pbp2x, and pbp2b genes, it is likely that they have arisen from a recent common ancestor. High-level resistance to expanded-spectrum cephalosporins was entirely due to alterations of penicillin-binding proteins (PBPs) 1a and 2x, since a mixture of the cloned pbp1a and pbp2x genes from the resistant strains could transform the susceptible strain R6 to the full level of cephalosporin resistance of the clinical isolates. Both PBP1a and PBP2x of these strains were more resistant to inhibition by cephalosporins than those of typical highly penicillin-resistant isolates. The pbp1a genes of CS109 and CS111 were identical in sequence, and the fourfold difference in their levels of resistance to cephalosporins was due to a Thr-550-->Ala substitution at the residue following the conserved Lys-Ser-Gly motif of PBP2x. This substitution was also the major cause of the 16-fold-lower resistance of CS111 to penicillin. The pbp2x gene of CS111, in an appropriate genetic background, could provide resistance to 16 micrograms of cefotaxime per ml but only to 0.12 microgram of benzylpenicillin per ml. Removal of the codon 550 mutation resulted in a pbp2x gene that provided resistance to 4 microgram of cefotaxime per ml and 4 microgram of benzylpenicillin per ml. The Thr-550-->Ala substitution in CS111 therefore appears to provide increased resistance to expanded-spectrum cephalosporins but a loss of resistance to penicillin.

171 citations


Journal ArticleDOI
TL;DR: Nasopharyngeal colonization was associated with an increased incidence of acute otitis media, and penicillin resistance was associated in this population of young children with higher rates of pneumococcal colonization.

149 citations


Journal ArticleDOI
TL;DR: A comprehensive national surveillance trial using 99 recruited microbiology laboratories in 48 of the 49 contiguous states or districts generated information from nearly 2000 enterococci, usually isolated from blood cultures, finding antimicrobial resistance occurred most often among the E. faecium isolates.

146 citations


Journal ArticleDOI
TL;DR: The ability of clindamycin and penicillin to modulate lipopolysaccharide-induced cytokine production in human peripheral blood mononuclear cells is investigated and results suggest that clind amycin affects protein synthesis in both prokaryotic and eukaryotic cells.
Abstract: The efficacy of an antibiotic in human or experimental infection is presumed to be proportional to its in vitro antimicrobial activity, yet antibiotics having comparable in vitro activity may have markedly different efficacies in vivo. For example, we have reported that clindamycin is more efficacious than penicillin in experimental gas gangrene caused by Clostridium perfringens in animals. To explain these differences, we compared the dynamics of bacterial killing and suppression of toxin synthesis. In addition, we investigated the ability of clindamycin and penicillin to modulate lipopolysaccharide-induced cytokine production in human peripheral blood mononuclear cells. Our results suggest that clindamycin affects protein synthesis in both prokaryotic and eukaryotic cells. These data may, in part, explain why the efficacy of clindamycin is greater than that of penicillin and demonstrate that clindamycin may be important immune modulator.

143 citations


Journal ArticleDOI
TL;DR: Meropenem is a parenteral carbapenem antibiotic which has excellent bactericidal activity in vitro against almost all clinically significant aerobes and anaerobes, and its high activity is explained by ease of entry into bacteria combined with good affinity for essential penicillin binding proteins, including those associated with cell lysis.
Abstract: Meropenem is a parenteral carbapenem antibiotic which has excellent bactericidal activity in vitro against almost all clinically significant aerobes and anaerobes. Its high activity is explained by ease of entry into bacteria combined with good affinity for essential penicillin binding proteins, including those associated with cell lysis. Breadth of spectrum is due, in part, to stability to all serine-based beta-lactamases, including those which hydrolyse third-generation cephalosporins. Meropenem has an antibacterial spectrum which is broadly similar to that of imipenem but, whilst slightly less active against staphylococci and enterococci, it is more active against Pseudomonas aeruginosa, all Enterobacteriaceae and Haemophilus influenzae. Amongst common human pathogens, only methicillin-resistant staphylococci and Enterococcus faecium are uniformly resistant to meropenem. The meropenem MICs for penicillin-resistant Streptococcus pneumoniae are higher than for penicillin-susceptible strains but the organisms remain susceptible. Clinical susceptibility in vitro to meropenem is defined by MICs of or = 16 mg/L define resistance; equivalent figures for zones of growth inhibition are > or = 14 (susceptible), 12-13 (intermediate) and < or = 11 (resistant) mm. Studies in guinea pig models of systemic infection and infections localised to the lungs, urinary tract and the central nervous system, some of which used immunocompromised animals, confirm the potential of meropenem demonstrated in vitro. These factors, combined with the human plasma, tissue or urinary concentrations of meropenem which exceed modal MICs for the pathogens isolated in clinical trials for most or all of the recommended 8 h dosing interval, predict that meropenem should be efficacious in the treatment of infections at many body sites.

Journal ArticleDOI
TL;DR: Rates of antimicrobial resistance have been increasing in bacteria responsible for community-acquired lower respiratory tract infections in the United States, and nearly 100% of clinical isolates of Moraxella catarrhalis now produce beta-lactamase, an enzyme that renders this pathogen resistant to such agents as penicillin, ampicillin, and amoxicillin.

Journal ArticleDOI
TL;DR: The sensor was used to quantify penicillin concentration produced during a Penicillium chrysogenum fermentation and accounts for the varying activity of the immobilized peniillinase at different pH values.
Abstract: An optical penicillin biosensor is described, based on the enzyme penicillinase. The sensor is fabricated by selective photodeposition of analyte-sensitive polymer matrices on optical imaging fibers. The penicillin-sensitive matrices are fabricated by immobilizing the enzyme as micrometer-sized particles in a polymer hydrogel with a covalently bound pH indicator. An array of penicillin-sensitive and pH-sensitive matrices are fabricated on the same fiber. This array allows for the simultaneous, independent measurement of pH and penicillin. Independent measurement of the two analytes allows penicillin to be quantitated in the presence of a concurrent pH change. An analysis was conducted of enzyme kinetic parameters in order to model the penicillin response of the sensor at all pH values. This analysis accounts for the varying activity of the immobilized penicillinase at different pH values. The sensor detects penicillin in the range 0.25-10.0 mM in the pH range 6.2-7.5. The sensor was used to quantify penicillin concentration produced during a Penicillium chrysogenum fermentation.

Journal ArticleDOI
TL;DR: It is concluded that multiple genetic clones of penicillin-resistant pneumococci can occur simultaneously in a single CCC, especially during periods of heavy antibiotic selection pressure.
Abstract: We obtained nasopharyngeal cultures for Streptococcus pneumoniae from 54 children ages 2 to 24 months attending an Omaha child-care center (CCC) in April 1994. Thirty-two (59%) of the 54 children were colonized with S. pneumoniae belonging to serotypes 23, 19, 6 and 11. Seventeen (53%) of the pneumococcal isolates were highly resistant to penicillin (minimal inhibitory concentration > or = 2.0 micrograms/ml; HR-SP) and 7 (22%) were intermediately resistant to penicillin (0.12 < or = minimal inhibitory concentration < or = 1.0 microgram/ml; IR-SP). Within each pneumococcal capsular serotype, there were 1 to 3 DNA subtypes based on pulsed field gel electrophoresis analysis. A single pulsed field gel electrophoresis strain predominated in most CCC rooms, suggesting horizontal transmission among cohorted children. Nasopharyngeal cultures obtained 4 months later revealed similar S. pneumoniae colonization rates (28 of 52, 54%); however, only 2 (7%) of 28 isolates were HR-SP and 11 (39%) were IR-SP. Colonization with resistant pneumococci persisted after 4 months in 4 (12%) of 34 children cultured on both occasions. Antibiotic use by attendees had decreased notably between the two sampling periods, suggesting that selective pressure within the CCC might contribute to seasonal variation in colonization rates with HR-SP and IR-SP. We conclude that multiple genetic clones of penicillin-resistant pneumococci can occur simultaneously in a single CCC, especially during periods of heavy antibiotic selection pressure. However, individual clones of penicillin-resistant S. pneumoniae may be spread from child to child, suggesting that colonization with penicillin-resistant S. pneumoniae should now be considered a CCC-associated phenomenon.

Journal ArticleDOI
TL;DR: This minireview focuses on the specific problems encountered in managing patients with penicillinand cephalosporin-resistant pneumococcal meningitis and discusses some therapeutic alternatives that have recently been explored.
Abstract: Since the isolation of the first penicillin-resistant Streptococcus pneumoniae strain in 1967 (23), there have been many reports of treatment failure in patients with pneumococcal infections caused by strains resistant to penicillin and other antimicrobial agents such as chloramphenicol, macrolides, trimethoprim-sulfamethoxazole, and the cephalosporins. As a result, the selection of antimicrobial agents for the treatment of infections caused by these organisms has become increasingly difficult. In particular, the emergence of pneumococci resistant to broad-spectrum cephalosporins has limited the choices of antibiotics for the treatment of pneumococcal meningitis. This minireview focuses on the specific problems encountered in managing patients with penicillinand cephalosporin-resistant pneumococcal meningitis and discusses some therapeutic alternatives that have recently been explored.

Journal ArticleDOI
TL;DR: Control of penicillin resistance among strains of Streptococcus pneumoniae will require innovative methods to reduce the selective pressure that results from widespread antibiotic use and to develop effective pneumococcal vaccines that are immunogenic in young infants.
Abstract: Penicillin resistance among strains of Streptococcus pneumoniae has emerged as an important worldwide problem. Beta-lactam-resistant pneumococci also can be resistant to erythromycin, trimethoprim/sulfamethoxazole and tetracycline and are uniformly susceptible to vancomycin and imipenem. Crowded conditions (e.g. daycare centers, hospitals, military barracks and prisons) and prior beta-lactam antibiotic therapy are the principal predisposing factors to colonization and disease. To date the two conditions caused by penicillin- and cephalosporin-resistant pneumococci that have been especially difficult to treat are acute otitis media and meningitis. Concentrations of beta-lactams in cerebrospinal fluid and middle ear fluid are usually inadequate to achieve prompt eradication of some intermediately resistant and most highly resistant pneumococcal strains. Use of unconventional therapeutic agents such as ceftriaxone or clindamycin for acute otitis media and vancomycin or rifampin for meningitis may be necessary. Control of this global problem will require innovative methods to reduce the selective pressure that results from widespread antibiotic use and to develop effective pneumococcal vaccines that are immunogenic in young infants.

Journal ArticleDOI
TL;DR: Rates of bacteremia due to highly penicillin-resistant viridans streptococci increased significantly and may have significant clinical implications in the choice of both antimicrobial prophylaxis and empirical antibiotic regimens.
Abstract: We prospectively studied 260 episodes of bacteremia that occurred over a 6-year period in neutropenic patients with cancer. Twenty-three episodes were caused by viridans streptococci. Thirteen (57%) of these strains were penicillin-resistant (MICs of penicillin ranged from 0.25 micrograms/mL to 8 micrograms/mL). Ten of the 13 penicillin-resistant strains (77%) were highly resistant to penicillin (MIC, > or = 4 micrograms/mL). Rates of bacteremia due to highly penicillin-resistant viridans streptococci increased significantly from zero episodes per 1,000 admissions in 1987 to 17 episodes per 1,000 admissions in 1992 (P = .003). In a comparison between penicillin-resistant and penicillin-susceptible viridans streptococci bacteremia, the administration of beta-lactam antibiotics during the previous 2 weeks was the only factor significantly associated with penicillin-resistant cases: 9 (69%) of 13 patients with penicillin-resistant bacteremia had received beta-lactams vs. 2 (20%) of 10 patients with penicillin-susceptible bacteremia (P = .036). These findings may have significant clinical implications in the choice of both antimicrobial prophylaxis and empirical antibiotic regimens.

Journal ArticleDOI
TL;DR: Beta-lactam agents included in the first group could be an acceptable alternative in the treatment of serious infections due to strains highly resistant to penicillin, although clinical experience is needed.
Abstract: A total of 410 strains of viridans group streptococci isolated consecutively from blood were tested by the microdilution method for in vitro susceptibility to 22 beta-lactam antibiotics. One hundred thirty-eight strains (33.6%) were resistant to penicillin with a MIC range of 0.25 to 8 micrograms/ml. MICs of all beta-lactam agents tested were higher for penicillin-resistant strains than for susceptible strains. These antibiotics were classified into three groups according to their in vitro activities (MICs at which 50 and 90% of the isolates are inhibited). Beta-Lactams of the first group (these included imipenem, cefpirome, FK-037, cefditoren, cefotaxime, ceftriaxone, and cefepime) showed activities higher than or similar to that of penicillin against penicillin-resistant viridans group streptococci. However, 80% of highly penicillin-resistant Streptococcus mitis organisms required cefotaxime and ceftriaxone MICs of > or = 2 micrograms/ml (range, 2 to 16 micrograms/ml). Beta-Lactams of the second group (cefpodoxime, ampicillin, amoxicillin-clavulanate, piperacillin, and cefuroxime) showed lower activities than penicillin. Finally, antibiotics of the third group (cephalothin, oxacillin, ceftazidime, cefixime, cefaclor, cefetamet, cefadroxil, cephalexin, and ceftibuten) showed poor in vitro activities. Therefore, some of the beta-lactam agents included in the first group could be an acceptable alternative in the treatment of serious infections due to strains highly resistant to penicillin, although clinical experience is needed.

Journal ArticleDOI
TL;DR: The study confirms the high levels of in vitro susceptibility of Bartonella agents to antibiotics and assesses in vitro the antibiotic susceptibilities of 14 Bartoneella isolates of the species B. elizabethae.
Abstract: We assessed in vitro the antibiotic susceptibilities of 14 Bartonella isolates of the species B. quintana, B. vinsonii, B. henselae, and B. elizabethae. Columbia agar base supplemented with 5% horse blood was used as the antibiotic assay medium. Bacterial growth could be evaluated within 5 days after incubation of the plates at 37 degrees C in a 5% carbon dioxide atmosphere. The MICs at which 90% of isolates are inhibited (MIC90s) were 0.06 microgram/ml for penicillin G and amoxicillin and 0.25 microgram/ml for ticarcillin and cefotaxime. The MIC90s of oxacillin and cephalothin were 4 and 16 micrograms/ml, respectively. The MIC90s ranged from 1 to 4 micrograms/ml for aminoglycosides. Erythromycin, doxycycline, and rifampin displayed MIC90s of 0.12, 0.12, and 0.25 microgram/ml, respectively. MIC90s were 1 and 5 micrograms/ml for trimethoprim-and sulfamethoxazole, respectively, 64 micrograms/ml for fosfomycin, and 16 micrograms/ml for colistin and vancomycin. The study confirms the high levels of in vitro susceptibility of Bartonella agents to antibiotics.

Journal ArticleDOI
TL;DR: Existing data suggest that rapid GAS antigen testing as an aid to clinical diagnosis can be very useful and when used appropriately, it is sensitive in detecting GAS-infected patients and is specific, specific, and cost-effective.

Journal ArticleDOI
TL;DR: The prevalence of pneumococcal resistance documented in Korea in this study is among the highest figures published to date.
Abstract: One hundred thirty-one strains of Streptococcus pneumoniae isolated from clinical specimens between January 1991 and April 1993 were serotyped and tested for susceptibility to 10 antimicrobials by the agar dilution method. Five serotypes (6A, 6B, 14, 19F, and 23F) accounted for 67% of all isolates. Seventy percent of isolates were not susceptible to penicillin, exhibiting either intermediate resistance (37%) or high-level resistance (33%); 82% of isolates from children and 59% of those from normally sterile body fluids were resistant to penicillin. A significantly increased rate of penicillin resistance (P < .01, Fisher's exact or chi 2 test) was associated with hospitalization, an age of < or = 15 years, ongoing antimicrobial therapy at the time of isolation of the organism, nosocomial acquisition, and several specific serotypes (6, 14, 19F, and 23F). No penicillin-resistant strain showed beta-lactamase activity. Various proportions of the penicillin-resistant strains also displayed resistance to cefaclor (89%), cefotaxime (82%), chloramphenicol (65%), erythromycin (52%), and ciprofloxacin (15%), but none was resistant to teicoplanin or vancomycin. The prevalence of pneumococcal resistance documented in Korea in this study is among the highest figures published to date.

Journal ArticleDOI
TL;DR: Mosaic penicillin-binding proteins (PBP) 1A, 2X and 2B genes were cloned from four clinical isolates of Streptococcus pneumoniae with levels of susceptibility toPenicillin with clearances to determine whether alterations to PBP1A,2X and2B alone were sufficient to attain high levelpenicillin resistance.
Abstract: Mosaic penicillin-binding proteins (PBP) 1A, 2X and 2B genes were cloned from four clinical isolates of Streptococcus pneumoniae with levels of susceptibility to penicillin ranging from 1.5 to 16 micrograms benzylpenicillin ml-1. In each instance it was possible to transform either the penicillin-sensitive laboratory strain R6 or a sensitive clinical isolate 110K/70 to the full level of penicillin resistance with these three penicillin-binding proteins alone. Until now it has not been possible to clearly determine whether alterations to PBP1A, 2X and 2B alone were sufficient to attain high level penicillin resistance.

Journal ArticleDOI
TL;DR: Potentially effective vaccines, such as the new polysaccharide-protein conjugate vaccines that will have efficacy in small children, are currently in early field trials and ultimately may be the best mechanism to deal with the spread of these organisms.

Journal ArticleDOI
01 Jul 1995-Allergy
TL;DR: The high percentage of subjects in this group who showed delayed skin test responses, taken together with the biopsy results, suggests that a lymphocyte‐mediated reaction occurred, and the possibility that other mechanisms may also have been involved cannot be ruled out.
Abstract: In patients treated with penicillins, adverse cutaneous reactions can occur within minutes or may take several days to develop. IgE antibody-mediated reactions are well documented, but other mechanisms may also be involved. In particular, nonimmediate reactions have not been studied extensively, and the purpose of the present work was to establish the incidence of such reactions among a large group of patients and to study the penicillins involved. A total of 380 subjects with a history of a cutaneous reaction following administration of a penicillin antibiotic was included in the study. Skin tests and specific IgE measurements (RAST) were carried out using various penicillins and penicillin-related reagents, and patients were also challenged with various penicillins. In some patients with delayed skin test responses, skin biopsies were carried out. The tests confirmed that 74 subjects (19.4% of total investigated) had suffered a cutaneous reaction to a penicillin derivative, and 29 of these subjects (7.6% of total or 39% of confirmed) showed evidence of having suffered a nonimmediate reaction. The latter group were identified by giving a positive delayed direct challenge, and in 65% of the cases a delayed skin test response was detected. In most cases, these responses were to amino penicillins. Skin biopsies showed a lymphomonocytic cell infiltrate. Nonimmediate reactions to penicillins are a reproducible phenomenon, suggesting that a specific mechanism is responsible. By direct challenge, 93% of responders were positive to amino penicillins (10.3% ampicillin, 82.7% amoxicillin), indicating a major role for these penicillins in nonimmediate reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: In this article, the PBP 2 gene (pbpB) was cloned from an expression library of a methicillin-susceptible strain of S. aureus (209P), and its entire sequence was compared with that of the pBPB gene from strains BB255, BB255R, and CDC6.
Abstract: In Staphylococcus aureus, penicillin-binding protein 2 (PBP 2) has been implicated in non-PBP 2a-mediated methicillin resistance. The PBP 2 gene (pbpB) was cloned from an expression library of a methicillin-susceptible strain of S. aureus (209P), and its entire sequence was compared with that of the pbpB gene from strains BB255, BB255R, and CDC6. Point mutations that resulted in amino acid substitutions near the conserved penicillin-binding motifs were detected in BB255R and CDC6, two low-level methicillin-resistant strains. Penicillin binding to PBP 2 in both BB255R and CDC6 is altered, and kinetic analysis indicated that altered binding of PBP 2 by penicillin was due to both lower binding affinity and more rapid release of bound drug. These structural and biochemical changes may contribute to the strains' resistance to beta-lactam antibiotics.

Journal ArticleDOI
TL;DR: The results indicate that the risk of treatment failure with cefuroxime axetil was increased in children with otitis media caused by S. pneumoniae when the penicillin MIC were greater than or equal to 2 mg/liter.
Abstract: Eighty-four children suffering from acute otitis media caused by Streptococcus pneumoniae were treated prospectively with cefuroxime axetil suspension (30 mg/kg of body weight twice daily for 8 days). The high incidence of isolates with decreased susceptibilities to penicillin (42 of 84 isolates) allowed us to establish a relationship between clinical success and the penicillin MICs for pneumococcal isolates. It was found that cefuroxime axetil is clinically effective in the treatment of acute otitis media caused by penicillin-susceptible and penicillin-intermediate strains of S. pneumoniae. The results indicate that the risk of treatment failure with cefuroxime axetil was increased in children with otitis media caused by S. pneumoniae when the penicillin MIC were greater than or equal to 2 mg/liter.

Journal ArticleDOI
TL;DR: It is suggested that encysted borreliae, granules, and the remaining blebs might be responsible for the ongoing antigenic stimulus leading to complaints of chronic Lyme bor Reliosis.
Abstract: Antibiotic therapy with penicillin, doxycycline, and ceftriaxone has proven to be effective for the treatment of Lyme borreliosis. In some patients, however, it was noticed that borreliae can survival in the tissues in spite of seemingly adequate therapy. For a better understanding of this phenomenon, we investigated the different modes of degeneration of Borrelia burgdorferi suspensions during a 96-h exposure to various antibiotics. By dark-field microscopy and ultrastructural investigations, increasing blebbing and the gradual formation of granular and cystic structures could be followed during the exposure time. Although antibiotic concentrations at the MIC at which 90% of organisms are inhibited after 72 h were 80% or even greater, motile organisms were still present after incubation with penicillin and doxycycline but not after incubation with ceftriaxone. By transmission electron microscopy, intact spirochetal parts, mostly situated in cysts, were seen up to 96 h after exposure with all three antibiotics tested. According to experiences from studies with other spirochetes it is suggested that encysted borreliae, granules, and the remaining blebs might be responsible for the ongoing antigenic stimulus leading to complaints of chronic Lyme borreliosis.


Journal ArticleDOI
TL;DR: It is concluded that penicillin resistant bacteria are often present in the microflora of acute dental infection.
Abstract: Pus aspirated from acute suppurative oral infections in 78 patients (age range 13-76 years) yielded a total of 331 bacterial strains consisting of 143 facultative anaerobes (predominantly Streptococcus spp.) and 188 strict anaerobes (predominantly Prevotella spp.). Seventy-five isolates (23%) were resistant to penicillin (MIC > 1 mg/L), 37 (11%) were resistant to ampicillin (MIC > 2 mg/L) and 16 (5%) isolates were resistant to amoxycillin/clavulanic acid (MIC > 2 mg/L). Samples from 43 (55%) of the patients yielded at least one penicillin resistant isolate and within this group 30 samples (73%) contained at least one strain which produced beta-lactamase. A history of antibiotic therapy during the 6 months before enrollment in the study did not influence the isolation of penicillin resistant bacteria. It is concluded that penicillin resistant bacteria are often present in the microflora of acute dental infection.

Journal ArticleDOI
TL;DR: It is proposed that empiric treatment of SPn meningitis in Australia should consist of high dose penicillin plus a third generation cephalosporin, with appropriate modification once the identification of the organism and its susceptibilities are confirmed.