Showing papers on "Penicillin published in 1993"

Clinical experience with penicillin skin testing in a large inner-city STD clinic

Abstract: Objective. —To establish (1) the prevalence of positive penicillin skin tests among outpatients with well-defined but variable history of penicillin allergy and (2) the reproducibility, safety, and negative predictive value of skin testing with benzylpenicilloyl polylysine (PPL) and a minor-determinant mixture (MDM). Design. —Serial consenting outpatients with current indications for penicillin therapy were skin-tested in duplicate with PPL and MDM. Subjects with negative skin tests (93% of those positive by history and 95% of those negative by history) received therapeutic courses of benzylpenicillin (81%) or ampicillin (19%). Negative predictive value of skin testing was established by 72-hour follow-up for adverse reactions to drug. Setting/Patients. —A total of 5063 consecutive, qualifying outpatients in a Baltimore, Md, sexually transmitted disease (STD) clinic. The study group was young (73% between 20 and 40 years old), 66% male, and 90% black; 25% had history of atopy. Follow-up was 94% complete. Results. —Positive skin tests were observed in 7.1% of 776 individuals with previous history of penicillin allergy and in 1.7% of 4287 subjects negative by history (P Conclusions. —Skin testing with both major and minor penicillin determinants is safe using current recommendations, and both reagents are necessary for maximizing the identification of sensitized subjects. Routine penicillin skin testing can facilitate the safe use of penicillin in 90% of individuals with a previous history of penicillin allergy. (JAMA. 1993;270:2456-2463)

Penicillin-Binding Protein Expression at Different Growth Stages Determines Penicillin Efficacy In Vitro and In Vivo: An Explanation for the Inoculum Effect

Abstract: Mechanisms to explain the "inoculum effect" have not been elucidated in gram-positive infections. A mouse model of group A streptococcal myositis was used to compare the efficacies of two beta-lactams, penicillin and ceftriaxone, and a protein synthesis inhibitor, clindamycin, at three different inoculum sizes. beta-lactams were more susceptible to inoculum effects than was clindamycin both in vivo and in vitro (P < .05). The large inocula were hypothesized to reach stationary phase of growth sooner than smaller inocula both in vitro and in vivo. The penicillin-binding protein (PBP) patterns from membrane proteins isolated from mid-log-phase and stationary-phase cultures of Streptococcus pyogenes were compared. Binding of radiolabeled penicillin by all PBPs was decreased in stationary cells; however, PBPs 1 and 4 were undetectable at 36 h. Thus, the loss of certain PBPs during stationary-phase growth in vitro may be responsible for the inoculum effect observed in vivo and may account for the failure of penicillin in both experimental and human cases of severe streptococcal infection.

Dilemmas in diagnosis and management of cephalosporin-resistant Streptococcus pneumoniae meningitis

Abstract: We recently managed an infant with meningitis caused by Streptococcus pneumoniae in whom ceftriaxone failed to sterilize the cerebrospinal fluid after 6 days of therapy. This strain, which had a penicillin minimal inhibitory concentration (MIC) of 2 micrograms/ml, appeared susceptible to ceftriaxone (MIC or = 2 micrograms/ml). The incidence of pneumococcal strains with cefotaxime MICs > or = 1.0 micrograms/ml has increased from 0 of 258 from 1981 to 1983 to 5 of 112 (4.5%) from 1991 to 1992. The definition of cephalosporin resistance for pneumococci requires modification and further studies of the antibiotic management of meningitis caused by such strains are needed because resistance to cephalosporins is increasing and the extended spectrum cephalosporins may be ineffective as sole therapy.

Synergistic effect of ethanolic extract of propolis and antibiotics on the growth of staphylococcus aureus.

Abstract: Ethanolic extract of propolis (EEP), known to possess marked antibacterial activity, was incubated with 8 different common antibiotics in culture medium containing a fixed amount of a standard strain of Staphylococcus aureus. The antibiotic compounds used were: penicillin G, doxycycline, streptomycin, cloxacillin, chloramphenicol, cefradine, ampicillin and polymyxin B. They were used in varying levels, ranging between 0.000005-125.0 micrograms/ml or units, resp. Firstly, their minimal inhibitory concentrations were established in the absence of EEP, than EEP was added in concentrations up to 600 micrograms/ml. EEP had a marked synergistic effect on the antibacterial activity of streptomycin and cloxacillin, and a moderate synergistic effect on the others, except ampicillin.

Penicillins. A current review of their clinical pharmacology and therapeutic use.

Abstract: The penicillins are a large group of bicyclic ring compounds which contain a 4-membered beta-lactam ring (penams) fused to a 5-membered thiazolidine ring. Benzylpenicillin (penicillin G) was the first natural penicillin with potent activity against all Gram-positive pathogens, Gram-negative cocci and some spirochaetes and actinomycetes. For the last 50 years benzylpenicillin has been the mainstay of therapy for serious pneumococcal, streptococcal, meningococcal and gonococcal infections. However, the past decade has seen the emergence of resistance in certain parts of the world, initially among the gonococci, and more recently among the pneumococci and meningococci. Discovery of the 6-aminopenicillinamic acid nucleus has led to considerable manipulation of the basic ring structure, resulting initially in the synthesis of ampicillin, and subsequently the other aminopenicillins, analogues, esters and prodrugs. These drugs have the advantages of improved oral bioavailability and superior activity against Haemophilus influenzae, certain Gram-negative bacilli, salmonellae, enterococci and Listeria monocytogenes, making these agents popular in the treatment of upper and lower respiratory tract infections and urinary tract infections. The increasing spread of bacterial resistance, particularly among Enterobacteriaceae and H. influenzae, has curtailed the usefulness of these drugs in these clinical settings. To counteract this problem, a number of agents combining a penicillin and a beta-lactamase inhibitor (e.g. clavulanic acid, tazobactam and sulbactam) have been developed. These inhibitors have no intrinsic antibacterial activity, but combining them with a penicillin (e.g. amoxicillin/clavulanic acid) confers greater stability to beta-lactamases and hence a broader spectrum of activity. The emergence of penicillinase-producing staphylococci that rendered benzylpenicillin ineffective also stimulated the search for penicillinase-resistant penicillins--methicillin and nafcillin, followed by the acid-stable isoxazolyl penicillins. These agents are now the principle antistaphylococcal treatment. Methicillin-resistant coagulase-negative staphylococci are currently a major cause of hospital sepsis, and are resistant to these latter agents. Enteric Gram-negative bacilli have been the predominant cause of serious hospital infections during the last 30 years. Further manipulation of the penicillin structure has resulted in compounds with broader activity against Gram-negative bacilli, particularly Pseudomonas aeruginosa, while retaining activity against Gram-positive pathogens. The carboxypenicillins were the first step in this direction, but have been largely superseded by the ureidopenicillins. These agents have better activity against P. aeruginosa, and are still effective against Gram-negative and Gram-positive bacteria, including enterococci and anaerobic organisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Post-antibiotic effects in experimental infection models: relationship to in-vitro phenomena and to treatment of infections in man

Abstract: Persistent suppression of bacterial growth, called the post-antibiotic effect (PAE), has been studied in six different animal infection models. Prolonged in-vivo PAEs are observed for all antimicrobials with staphylococci and for imipenem and inhibitors of protein and nucleic acid synthesis with streptococci and Gram-negative bacilli. Penicillins and cephalosporins produce short or no in-vivo PAEs with these latter organisms. The presence of neutrophils prolongs the in-vivo PAEs found with aminoglycosides and quinolones. Simulation of human pharmacokinetics also enhances the duration of in-vivo PAE for aminoglycosides. In-vivo PAEs tend to be longer than those observed in vitro. The in-vitro PAE for penicillin with streptococci has been observed in vivo in only one of four experimental infection models. The presence of a prolonged in-vivo PAE can allow wider dosing intervals. The primary clinical application of the in-vivo PAE has been with once-daily dosing of aminoglycosides.

Is penicillin G an adequate initial treatment for aspiration pneumonia? A prospective evaluation using a protected specimen brush and quantitative cultures.

Abstract: To evaluate the bacteriology of early aspiration pneumonia using a protected specimen brush and quantitative culture techniques, and whether penicillin G is adequate as initial treatment pending culture results. 52 patients (of which 45 required mechanical ventilation) meeting usual clinical criteria for aspiration pneumonia were prospectively included. On admission, patients were given intravenous penicillin G and a protected specimen brush was performed ≤48 h after. Cultures of the brush were negative (<103 CFU/ml) in 33 patients (1 had blood cultures positive withS. pneumoniae) and positive (≥103 CFU/ml) forS. pneumoniae in 2 patients. Seventeen patients had a positive culture (≥103 CFU/ml) for at least one penicillin G resistant microorganism, with a total of 20 organisms (S. aureus: 6;H. influenzae: 2;Enterobacteriaceae: 8;P. aeruginosa: 3;C. albicans: 1). In 4 of these patients, a penicillin-sensitive pathogen was also recovered in significant concentrations (S. pneumoniae: 2;Streptococcus sp.: 2). These 17 patients with a resistant pathogen did not differ from the 35 other patients with respect to need for ventilatory support and mortality rate. By contrast, they were older (61.1±21.9 vs 42.9±18.8 years;p<0.005) and required longer mechanical ventilation (6.1±4.6 vs. 3.5±2.7 days;p<0.03) and hospitalization (11.2±8.8 vs. 6.7±4.7 days;p<0.02). Of 17 patients 12 with penicillin G resistant organisms versus 0/35 without, were in-hospital patients and/or had a digestive disorder (p<0.001). The broad range of offending organisms seen in early aspiration pneumonia precludes use of any single empiric regimen, making protected specimen brush mandatory in many patients. Nevertheless, the involvement ofS. pneumoniae in a notable proportion of our patients suggests that routine penicillin prophylaxis after early aspiration (at least in most patients with community-acquired aspiration) is warranted given the potential severity of pneumococcal sepsis in such patients.

Prophylactic administration of penicillins for endocarditis does not reduce the incidence of postextraction bacteremia.

Abstract: Sixty healthy patients were randomized to receive placebo, penicillin V (2 g), or amoxicillin (3 g) 1 hour before dental extraction was performed. Blood samples for microbiological investigation were collected before, during, and 10 minutes after surgery and were processed by lysis filtration under anaerobic conditions. There was no statistical difference among patients in the placebo group, the penicillin-V group, and the amoxicillin group in terms of incidence or magnitude of bacteremia due to viridans streptococci or anaerobic bacteria during extraction or 10 minutes after the procedure. The overall incidence rates of bacteremia after dental extraction were 95%, 90%, and 85%, respectively, for the three groups. For > 90% of 126 strains of viridans streptococci tested, the MICs of penicillin V and ampicillin were < or = 0.125 mg/L. The protective effect of prophylactically administered penicillins must be due to interference with crucial steps in the development of endocarditis (other than the transient bacteremia that occurs initially).

Penicillin-resistant systemic pneumococcal infections in children: a retrospective case-control study

Abstract: Objective To determine whether there are any risk factors that differentiate children with systemic infections due to Streptococcus pneumoniae relatively or fully resistant (minimum inhibitory concentration > 0.1 microgram/mL) to penicillin from those children with infections due to S pneumoniae susceptible to penicillin. Design Retrospective case-control study. Setting A large children's hospital. Participants Forty-three children with systemic penicillin-resistant S pneumoniae infections identified at Texas Children's Hospital over the 51-month period from January 1989 through March 1993. Each case had one or two controls matched only for age and date of S. pneumoniae infection. Sixty-six controls were selected from a group of 341 children with susceptible isolates. Outcome measures Variables compared included gender, race, diagnosis, underlying conditions, past hospitalization, geographic area of residence, antibiotic use in past month, amoxicillin-clavulanic acid use in past month, and outcome. Results Thirty-seven patients (86%) had relatively resistant isolates (minimum inhibitory concentration range 0.125 to 1.0 microgram/mL) and six patients (15%) had fully resistant isolates (minimum inhibitory concentration range 2.0 to 8.0 micrograms/mL). Thirty-three percent of the cases vs 36% of the controls had underlying conditions. Seventy-one percent of the cases vs 39% of the controls had received antibiotics in the previous month. Compared with their matched controls, the patients with penicillin-resistant systemic pneumococcal infections were more likely (P = .02) to have received a course of antibiotics within the month prior to their infection. Conclusion The only identified associated risk factor in children who developed a systemic penicillin-resistant pneumococcal infection appears to have been the use of antibiotics within the month prior to their infection.

The frequency of skin test reactions to side-chain penicillin determinants

Abstract: Background: Skin testing for immediate hypersensitivity to penicillins is usually carried out with reagents prepared from benzylpenicillin, and it is believed that side-chain-specific reactions to semisynthetic derivatives are rare. Because some experimental and clinical data suggest that antibodies can be induced to immunogenic epitopes on the side chains of penicillins, we looked for side-chain-specific reactions to skin testing in patients with a history of allergy to penicillins or semisynthetic penicillins. Methods: One hundred twelve patients with a clinical history of allergic reactions to penicillins and other semisynthetic penicillins were skin tested an average of 4.9 ± 0.7 years after their reactions with the major and minor determinants of benzylpenicillin and minor determinant mixtures of ampicillin, amoxicillin, or cloxacillin. Results: In these patients the most common clinical reactions were urticaria and angioedema (36.6%) and exanthema (48.8%). It was found that 21 cases (18.8%) still exhibited immediate hypersensitivity reactions on skin testing. But of these 21 patients, skin test reactivity was limited in 47.6% to the semisynthetic penicillin reagents derived from ampicillin, amoxicillin, or cloxacillin; that is, skin tests were negative with the benzylpenicillin derivatives. Ampicillin and amoxicillin were the semisynthetic l3-lactams causing most clinical reactions (24.1% and 33.9%, respectively), and ampicillin was the most common penicillin derivative to which skin test reactivity occurred (38.1%), other than the benzylpenicillin derivatives (52.3%). Conclusions: IgE antibodies appear therefore to discriminate between benzylpenicillin and ampicillin or other semisynthetic penicillins in a significant proportion of patients allergic to penicillin. Although it has not been proved that side-chain-specific skin reactivity implies the presence of clinically significant immediate hypersensitivity to semisynthetic penicillins, it is possible that side-chain-specific reagents may be required to exclude possible immediate hypersensitivity to the penicillins in patients who reacted to these antibiotics clinically.

Why is Chlamydia sensitive to penicillin in the absence of peptidoglycan

Abstract: Most eubacteria are sensitive to penicillin because the antibiotic inhibits synthesis of peptidoglycan, an essential constituent of their cell walls. A few eubacteria have no measurable peptidoglycan, and, with one exception, they are not susceptible to penicillin. The exception is the genus Chlamydia whose members are just as sensitive to penicillin as peptidoglycan-containing bacteria. A numbers of ways to resolve this anomaly, penicillin sensitivity without peptidoglycan, are proposed. It is concluded that there are serious objections to each one and that the chlamydial anomaly remains unresolved. However, examination of the relation between penicillin and chlamydiae is useful because it reveals how little is known of the evolutionary history of penicillin, penicillin-binding proteins, and peptidoglycan.

Infections due to penicillin-resistant pneumococci. Clinical, epidemiologic, and microbiologic features.

Abstract: Pneumococcal infection remains a common cause of serious morbidity and mortality throughout the world. Until recently, clinical isolates of pneumococci that were penicillin resistant were rare. However, 4% to 5% of the clinical isolates in the United States were recently found to be either intermediately resistant or highly resistant to penicillin. Clinicians in every field of medicine must therefore be better informed regarding penicillin-resistant pneumococcal infections to minimize their attendant morbidity and mortality and increase compliance with preventive measures. We reviewed the molecular, genetic, and epidemiologic aspects of penicillin-resistant pneumococcal infections, with emphasis on their microbiologic and clinical features.

Changes in the prevalence of subgingival enteric rods, staphylococci and yeasts after treatment with penicillin and erythromycin.

Abstract: The changes in the balance of microbial flora in the periodontium after antibiotic treatment were investigated in a blind study. The prevalence of gram-negative enteric rods, staphylococci and yeasts was followed before and during penicillin or erythromycin treatment of 72 periodontitis patients without periodontal cleaning. The prevalence of subgingival coagulase-positive staphylococci increased significantly following systemic penicillin therapy. After systemic erythromycin therapy, the prevalence of subgingival gram-negative enteric rods increased. Ten of 24 (42%) patients receiving systemic penicillin therapy developed clinical evidence of periodontal abscesses. In the absence of conventional mechanical cleaning, systemic administration of penicillin and erythromycin antibiotic to patients with pre-existing periodontitis may lead to periodontal superinfection with opportunistic organisms.

Selective generation of CD8+ T‐cell clones from the peripheral blood of patients with cutaneous reactions to beta‐lactam antibiotics

Abstract: Summary The presence, phenotype, and functional characteristics of peripheral blood penicillin-specific T lymphocytes in individuals with cutaneous allergic reactions to penicillin were investigated using in vitro long-term culture techniques. Peripheral blood mononuclear cells from two penicillin-allergic patients were stimulated in vitro with penicillin, and T-cell blasts were clonally expanded by limiting dilution. Seven T-cell clones were derived, all of which were CD3+ CD4− CD8+ HLA-DR+, and produced IL-2 and IFN-γ upon stimulation. T-cell proliferation required the presence of antigen and autologous, but not allogeneic, antigen-presenting cells. In addition to the parent compound, the T-cell clones also developed a proliferative response to penicilloyl, the major metabolite of penicillin. The cloned T-cell lines were found to exhibit marked suppressor activity for Con A mitogenesis. The observed suppressor activity required cell-to-cell contact, as supernatants from these T-cell clones had no comparable inhibitory effect. These findings indicate that there is a predominance of penicillin-specific CD8+ T cells in the peripheral blood of individuals sensitized to beta-lactam antibiotics.

The isopenicillin-N acyltransferase of Penicillium chrysogenum has isopenicillin-N amidohydrolase, 6-aminopenicillanic acid acyltransferase and penicillin amidase activities, all of which are encoded by the single penDE gene

Abstract: The isopenicillin-N acyltransferase of Penicillium chrysogenum catalyzes the conversion of the biosynthetic intermediate isopenicillin N to the hydrophobic penicillins. The isopenicillin-N acyltransferase copurified with the acyl-CoA:6-aminopenicillanic acid (6-APA) acyltransferase activity which transfers an acyl residue from acyl-CoA derivatives (e.g. phenylacetyl-CoA, phenoxyacetyl-CoA) to 6-APA. Other thioesters of phenylacetic acid were also used as substrates. An amino acid sequence similar to that of the active site of thioesterases was found in the isopenicillin-N acyltransferase, suggesting that this site is involved in the transfer of phenylacetyl residues from phenylacetyl thioesters. Purified isopenicillin-N acyltransferase also showed isopenicillin-N amidohydrolase, penicillin transacylase and penicillin amidase activities. The isopenicillin-N amidohydrolase (releasing 6-APA) showed a much lower specific activity than the isopenicillin-N acyltransferase of the same enzyme preparation, suggesting that in the isopenicillin-N acyltransferase reaction the 6-APA is not released and is directly converted into benzylpenicillin. Penicillin transacylase exchanged side chains between two hydrophobic penicillin molecules; or between one penicillin molecule and 6-APA. The penicillin amidase activity is probably the reverse of the biosynthetic acyl-CoA:6-APA acyltransferase. Four P. chrysogenum mutants deficient in acyl-CoA:6-APA acyltransferase lacked the other four related activities. Transformation of these mutants with the penDE gene restored all five enzyme activities.

Genetic diversity of penicillin-binding protein 2B and 2X genes from Streptococcus pneumoniae in South Africa.

Abstract: Streptococcus pneumoniae (the pneumococcus) is believed to have developed resistance to penicillin by the production of altered forms of penicillin-binding proteins (PBPs) that have decreased affinity for penicillin. Sixty-eight clinical isolates of serogroup 6 and 19 pneumococci (MICs, or = 0.06 micrograms/ml. Analysis of the PBP 2X gene revealed a greater diversity in the population with 26 variant genes, including some diversity among susceptible isolates. Discrete profiles of both genes were found only within narrow bands of the penicillin MIC, so that the gene pattern predicted the MIC. PBP 2X gene variation and the lack of variability among PBP 2B genes in pneumococci inhibited at low MICs confirm that PBP 2X alteration may be responsible for low-level penicillin resistance, while alterations in both PBP 2B and PBP 2X are required for high-level resistance. The extensive diversity of PBP genes in South African serogroup 6 and 19 strains suggests that altered PBP genes have arisen frequently in this population.

Optimum treatment of staphylococcal infections.

Abstract: Serious staphylococcal infections remain a significant clinical problem despite advances in antibacterial therapy. Resistance to penicillin is common and methicillin-resistant staphylococci have become troublesome nosocomial pathogens in many institutions. Penicillinase-resistant penicillins (e.g. flucloxacillin, cloxacillin and oxacillin) are the preferred drugs for all methicillin-susceptible staphylococcal infections, although first generation cephalosporins, beta-lactam/beta-lactamase inhibitor combinations, clindamycin, and occasionally erythromycin and cotrimoxazole (trimethoprim/sulfamethoxazole) are alternatives. Serious infections due to methicillin-resistant staphylococci should be treated with parenteral vancomycin. Teicoplanin, where available, is a suitable alternative. Rifampicin, fusidic acid and some fluoroquinolones may be useful oral alternatives, although resistance develops rapidly if they are used as single agents. Cotrimoxazole and minocycline have also proven useful when strains are susceptible. Staphylococcal toxic shock syndrome often requires aggressive resuscitation and anti-staphylococcal therapy for generally 10 to 14 days. Staphylococcus aureus bacteraemia remains a life-threatening condition which, in all but one-third of cases, is associated with an underlying septic focus such as endocarditis, osteomyelitis or occult abscess. Differentiating between complicated and uncomplicated bacteraemia is critical to define the appropriate treatment regimen. Serious staphylococcal sepsis such as endocarditis and acute osteomyelitis generally requires prolonged (4 to 6 weeks) antibiotic treatment. Coagulase-negative staphylococci are the commonest cause of prosthetic device infection, and generally require prolonged therapy with an agent to which they have proven to be sensitive, e.g. a penicillinase-resistant penicillin or vancomycin. Removal of infected foreign or prosthetic material, and drainage of deep collections remain a critical aspect of all therapy.

Trends in antimicrobial utilization at a tertiary teaching hospital during a 15-year period (1978-1992).

Abstract: Background: Antimicrobials are a major part of hospital pharmacy budgets and must be considered in resource planning and spending projections. Logically, trends in antimicrobial usage should be linked to trends in resistant pathogens. Objective: To examine long-term trends in antimicrobial use over a 15-year period (1978 to 1992) and contrast them with changes in pathogens causing nosocomial bacteremia. Setting: A 900-bed, tertiary care teaching hospital. Methods: Pharmacy records were reviewed to identify parenteral antimicrobial agents administered to adult inpatients. Results were expressed in average daily adult doses per 1,000 patient days. Results: Chloramphenicol use decreased, while use of penicillin G, antistaphylococcal penicillins, first-generation cephalosporins, and aminoglycosides remained relatively stable. In contrast, there was a sharp increase in the use of second- and third-generation cephalosporins (7-fold and 6.5-fold increase, respectively), vancomycin (161 -fold increase), metronidazole (32-fold increase) and amphotericin B (35-fold increase). The proportion of nosocomial bacteremias due to methicillin-resistant gram-positive bacteria rose, but gentamicin resistance in gram-negatives remained at low levels. During the past 14 years, the percentage of patients receiving at least one parenteral antimicrobial rose from 23% to 44%. Among patients receiving antimicrobials, the average number of different agents used per patient increased from 1.8 to 2.1 Conclusions: If newer agents were available, use of older agents usually declined. If newer alternatives were not available, use of older agents rose sharply. The increased use of antimicrobials in adults was related to the expanded proportion of patients receiving these agents.

Duration of Positive Throat Cultures for Group A Streptococci After Initiation of Antibiotic Therapy

Abstract: Objective. To determine if it is appropriate to recommend that patients with group A β-hemolytic streptococcal pharyngitis, who are clinically well by the morning after starting antibiotic treatment, can return to school or day care, or if they should wait until they have completed 24 hours of antibiotics as recommended by the American Academy of Pediatrics Committee on Infectious Diseases. Methods. We examined the duration of positivity of the throat culture after antibiotics were begun as a means of assessing the potential risk of transmission to close school contacts. Forty-seven children (4 to 17 years of age) with pharyngitis and a positive throat culture for group A streptococci in an outpatient, staff model health maintenance organization clinic were enrolled and were randomly selected to receive therapy with either oral penicillin V, intramuscular benzathine penicillin G, or oral erythromycin estolate. Additional throat cultures were obtained and clinical findings were recorded for each child during three home visits in the 24 hours after their initial clinic visit. Acute and convalescent sera were obtained for determination of anti-streptolysin O and anti-DNase B titers. Results. Seventeen (36.2%) of the 47 patients had a positive culture the morning after initiating antibiotic therapy. However, thirty-nine (83%) of the patients became "culture negative" within the first 24 hours. Neither the time interval to the first negative culture nor the presence or absence of group A streptococcal organisms on any single convalescent culture could be predicted by clinical findings. Six of the eight children who failed to convert to a "negative" throat culture within 24 hours of initiating therapy were receiving erythromycin. We could detect no difference in either time to conversion to a negative culture or the presence of a positive culture 24 hours after starting antibiotics between those who demonstrated a significant antibody increase and those who did not. Conclusion. The data from this study strongly suggest that children with group A β-hemolytic streptococcal pharyngitis should complete a full 24 hours of antibiotics before returning to school or daycare.

Azithromycin versus penicillin V for the treatment of early lyme borreliosis

Abstract: In a randomized multicenter therapeutic trial, 32 patients with erythema migrans received oral azithromycin 500 mg once daily and 33 patients received phenoxymethylpenicillin (penicillin V) 1 million U three times daily for 10 days Follow-up was for a median of 17 (range 3–32) months Four weeks after initiation of therapy, 20 (62%) patients given azithromycin and 17 (51%) patients given penicillin V were completely free of all signs and symptoms and did not develop new ones subsequently (no significant difference) Three months after initiation of therapy, the corresponding figures were 25 (78%) azithromycin and 28 (85%) penicillin V recipients (no significant difference) There were only minor sequelae such as arthralgia, headache, fatigue, stiff neck and dysesthesia Azithromycin led to a significantly faster resolution of the erythema migrans than penicillin V (p<0001) Significantly more patients with more severe compared with mild initial disease had an elevated IgM antibody titer prior to therapy (p<0001) Usually mild to moderate side effects occurred in 12 patients given azithromycin and five patients given penicillin V (p<005) Azithromycin appears to be as effective as penicillin V for the treatment of early Lyme borreliosis and it seems to clear the erythema migrans more promptly

Multicentre evaluation of azithromycin and penicillin V in the treatment of acute streptococcal pharyngitis and tonsillitis in children

Abstract: Of 96 children (aged 2-12 years) with either acute pharyngitis or acute tonsillitis, 49 received a single daily dose of azithromycin 10 mg/kg (maximum 500 mg) for three days, and 47 received penicillin V at a dose of 125 mg or 250 mg qid (depending on body weight) for ten days. Clinical assessments and laboratory safety tests were performed during and after therapy. Before enrollment, all patients were screened for group A beta-haemolytic streptococci (GABHS) with a rapid test, and a throat swab was taken for confirmatory culture. The presence of GABHS at baseline was confirmed in 41 azithromycin- and 44 penicillin V-treated patients. Cure or improvement was seen in 98% and 100% of azithromycin- and penicillin V-treated patients, respectively. At day 11, bacterial eradication was achieved in 39/41 (95%) azithromycin-treated patients, 38 (93%) of whom were considered clinically cured, while one patient (2%) relapsed. In the penicillin V group, 42/44 (95%) had GABHS eradicated, with 41 (93%) clinically cured and three patients (7%) improved. The remaining two patients in each group were clinically cured despite persistence of Streptococcus pyogenes. At follow-up evaluation (day 30), re-occurrence was observed in 5/37 (14%) and 3/40 (8%) of azithromycin- and penicillin V-treated patients, respectively; all patients were asymptomatic. Both drugs were well-tolerated with only two patients in the azithromycin group complaining of side effects. Treatment related laboratory test abnormalities were observed in 6/47 (13%) and 4/45 (9%) azithromycin- and penicillin V-treated patients, respectively, but none was judged to be clinically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of therapy with hyperbaric oxygen for experimental infection with Clostridium perfringens.

Abstract: The effects of inoculum size and treatment delays on the efficacy of hyperbaric oxygen (HBO) were evaluated in a murine model of Clostridium perfringens myositis in which the infection was treated with an HBO regimen identical to that used for humans. The efficacies of treatment with penicillin, metronidazole, or clindamycin--alone or in combination with HBO--were also assessed. Survival was inversely related to the size of the bacterial inoculum used for challenge, and delays in treatment markedly reduced the efficacies of all single and combination regimens. When animals were challenged with > 10(8) colony-forming units, survival was significantly higher among those treated with clindamycin or metronidazole than among those treated with penicillin. HBO alone did not improve survival at any inoculum tested. However, when administered early, HBO plus metronidazole or penicillin demonstrated significant additive efficacies in animals challenged with > or = 10(9) organisms. Clindamycin was more effective at the higher inocula than penicillin, metronidazole, or HBO, and its superior efficacy was not further enhanced by adjunctive therapy with HBO.

Acute otitis media; comparative therapeutic results of sulphonamide and penicillin administered in various forms.

Abstract: (1993). Acta Oto-Laryngologica: 75 Years. Acta Oto-Laryngologica: Vol. 113, No. 1, pp. 1-2.

Invasive pneumococcal disease in central Oklahoma : emergence of high-level penicillin resistance and multiple antibiotic resistance

Abstract: Relatively penicillin-resistant pneumococci have caused 10% of invasive pneumococcal disease in central Oklahoma during the last decade, but almost no high-level penicillin or other antibiotic resistance has been described. This study evaluated antibiotic susceptibility and serotype distribution in invasive pneumococcal disease in the Oklahoma City metropolitan area (1990 population 848,000). A total of 144 cases of invasive infection was collected in 1 year (17 with meningitis, 120 with other bacteremic infections, and 7 with other invasive infections), for a rate of 16.9/100,000 (95% confidence interval [CI], 14.0-19.5). For the population aged > or = 60, invasive pneumococcal disease rates were higher among nursing home residents (352/100,000) than among nonresidents (25.6/100,000; relative risk, 13.7; 95% CI, 7.7-24.7). Antibiotic-resistant organisms caused 19.4% of the cases: relative penicillin resistance, 7.6%; high-level penicillin resistance, 1.4% (2 cases), and 11% resistance to erythromycin, trimethoprim-sulfamethoxazole, or both, with 5% sharing both resistances plus a MIC of penicillin of 0.06 microgram/mL.

Effectiveness of norfloxacin and ofloxacin for treatment of gonorrhoea and decrease of in vitro susceptibility to quinolones over time in Rwanda

Abstract: OBJECTIVE--To study the effectiveness of single-dose norfloxacin and ofloxacin in the treatment of gonococcal urethritis in men, and to monitor in vitro antimicrobial susceptibility to these antibiotics over time. SETTING--Centre Medico-Social de Bilyogo, Kigali, Rwanda. The only clinic in Rwanda using quinolones for the treatment of gonorrhoea. METHODS--As part of a monitoring programme, men with gonococcal urethritis were evaluated after treatment with norfloxacin (800 mg) in 1986 and 1987, and after treatment with ofloxacin (400 mg) in 1989. RESULTS--Neisseria gonorrhoeae was eradicated from the urethra from 96.0% (189/197) and from 97.1% (166/171) men treated with norfloxacin and ofloxacin, respectively. Overall 38.2% of the pretreatment isolates produced penicillinase (PPNG isolates) and 20.4% (44/216) of the tested non-PPNG isolates were chromosomally resistant to penicillin (MIC > or = 2.0 mg/l). Resistance to tetracycline and thiamphenicol was common in both PPNG and non-PPNG and increased considerably in 1989. All isolates were susceptible to kanamycin, spectinomycin, ceftiaxone, norfloxacin, ofloxacin and ciprofloxacin. However, a higher number of isolates recovered in 1989 showed decreased susceptibility to the quinolones. Treatment failure occurred more often in subjects with isolates having MIC values > or = 0.06 mg/L of norfloxacin (p = 0.006). Seven out of 13 patients who did not respond to therapy had no signs nor symptoms of urethritis. CONCLUSION--Quinolone antibiotics are now indicated as a first line treatment of gonorrhoea in countries with a problem of antimicrobial multiresistance. However, antimicrobial susceptibility to the quinolones may decrease rapidly, and close monitoring of the in vitro susceptibility of N gonorrhoeae and the clinical effectiveness of the antibiotics is imperative.