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We reported the case of tonsillitis treatment in a 17-years-old boy with use of chemical non-antibiotic preparations, plant derived products and antibiotic benzathine phenoxymethylpenicillin. The antimicrobial agents for treatment were selected on the basis of their activity against a disease agent, the group A β-hemolytic strain Streptococcus pyogenes BS1 isolated from a patient. The bacterium was susceptible in vitro to β-lactams, with largest zones conditioned by penicillin G and benzathine phenoxymethylpenicillin discs, to fluoroquinolones and to cephems, with exception of cefazolin. Lincosamide clindamycin, macrolide spiramycin, aminoglycoside gentamicin, erythromycin, tetracycline and combination of sulfamethoxazole and trimethoprim were inactive against this bacterium. The Streptococcus pyogenes BS1 demonstrated intermediate susceptibility to the cephalosporin cephalexin, fluoroquinolone lomefloxacin and glycopeptide vancomycin. Non-antibiotic preparations were evaluated against Streptococcus pyogenes BS1 also. Among them "Stomatidin", "Chlorophyllipt", and phages of "Pyofag" were more effective than "Decatylen", "Decasan" and "Furadonin" in vitro. The antimicrobial applications of "Stomatidin", "Chlorophyllipt" and phages of "Pyofag" in the patient were less effective compared to the result of antibiotic benzathine phenoxymethylpenicillin treatment. Complete recovery of the patient was achieved with use of this antibiotic and Calendula flower extract as an local anti-inflammatory agent.

The recognition and interaction of FEZ-1 from Legionella (FEZ-1) with penicillin V(PV) and cefoxitin(CFX) were investigated using fluorescence spectra in combination with molecular dynamics simulation (MD). The results revealed that the CFX bind with FEZ-1 in stronger interaction and induced larger conformational change than PV, despite all being forced by the electrostatic interaction and along with the changing in an environment of amino acid residues as well as the polypeptide skeleton inside the FEZ-1. Moreover, only the loop1, loop2, and N-terminal were observed locating near the binding pocket of FEZ-1, consisting of a flexible "gate-like" zone with better adaptability that controlled the entrance of antibiotic into the pocket by allowing the newly introduced antibiotic to match the pocket better through the conformational changes of these three substructures in the binding procedure. The current study may provide some valuable information on the antibiotic hydrolytic process by metallo-beta-lactamase and thus the references for the development of new antibiotics for super bacteria., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The antibiotics dicloxacillin and flucloxacillin induce cytochrome P450-dependent metabolism of warfarin. We explored the influence of these drug-drug interactions on the clinical effectiveness of warfarin therapy due to atrial fibrillation or heart valve replacement. Using the population-based Danish registers, we performed a propensity-score matched cohort study including around 50,000 episodes of dicloxacillin/flucloxacillin matched to phenoxymethylpenicillin and to no antibiotic, respectively. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) by comparing 21-day (days 7-28) risks of ischemic stroke/systemic embolism (SE) following initiation of each exposure. When compared with phenoxymethylpenicillin, dicloxacillin/flucloxacillin was associated with an HR of ischemic stroke/SE of 2.09 (95% CI 1.51-2.90; strongest for dicloxacillin (HR 2.17; 95% CI 1.56-3.02)). Use of an untreated comparator strengthened the association (HR 2.84; 95% CI 1.97-4.09). Dicloxacillin should be used with caution in patients receiving warfarin. This may also apply to flucloxacillin; however, more data on the risks associated with flucloxacillin exposure during warfarin therapy are needed., (© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.)

Objectives: Antibiotic overuse has led to the global emergence of antimicrobial-resistant bacteria, and children are among the most frequent users of antibiotics. Most studies with broad-spectrum antibiotics show a severe impact on resistome development in patients. Although narrow-spectrum antibiotics are believed to have fewer side effects, their impact on the microbiome and resistome is mostly unknown. The aim of this study was to investigate the impact of the narrow-spectrum antibiotic phenoxymethylpenicillin (penicillin V) on the microbiome and resistome of a child treated for acute otitis media., Methods: Oral and faecal samples were collected from a 1-year-old child before (Day 0) and after (Days 5 and 30) receiving penicillin V for otitis media. Metagenomic sequencing data were analysed to determine taxonomic profiling using Kraken and Bracken software, and resistance profiling using KMA in combination with the ResFinder database., Results: In the oral samples, antimicrobial resistance genes (ARGs) belonging to four classes were identified at baseline. At Day 5, the abundance of some ARGs was increased, whereas some remained unchanged and others could no longer be detected. At Day 30, most ARGs had returned to baseline levels or lower. In the faecal samples, seven ARGs were observed at baseline and five at Day 5. At Day 30, the number of ARGs had increased to 21., Conclusions: Following penicillin V, we observed a remarkable enrichment of the aecal resistome, indicating that even narrow-spectrum antibiotics may have important consequences in selecting for a more resistant microbiome., (Copyright © 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.)

β‑Lactam antibiotics are among the most widely used antibiotics in human medicine and their effects on the aquatic environment - concerning bacterial resistance - are controversially discussed. This study focused on the photolysis of the four β‑lactam antibiotics - amoxicillin, ampicillin, penicillin V and piperacillin - under simulated environmental conditions. It was observed that all investigated β‑lactam antibiotics are photolytically degradable by simulated sunlight (1 kW/m 2 ) with half-lives between 3.2 and 7.0 h. Structure elucidation of transformation products performed with liquid chromatography coupled to high resolution mass spectrometry showed that the hydrolysis of the β‑lactam ring is the primary transformation reaction, followed by the elimination of carboxylic and dimethyl thiazolidine carboxylic acid. Growth inhibition tests on Bacillus subtilis showed the loss of bactericide activity of irradiated solutions of amoxicillin, ampicillin and piperacillin, suggesting the transformation of the β‑lactam ring is responsible for the antibiotic effect. In contrast, the solutions of penicillin V did not show any decline of the antibacterial activity after photolytic degradation, probably due to the formation of still active epimers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: In vitro studies have demonstrated that formation of reactive oxygen species (ROS) contributes to the effect of bactericidal antibiotics. The formation of ROS is not restricted to bacteria, but also occurs in mammalian cells. Oxidative stress is linked to several diseases. This study investigates whether antibiotic drugs induce oxidative stress in healthy humans as a possible mechanism for adverse reactions to the antibiotic drugs., Methods: This study contains information from two randomised, controlled trials. Participants underwent 1 week treatment with clarithromycin, trimethoprim, phenoxymethylpenicillin (penicillin V), or placebo. Oxidative modifications were measured as 24-h urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and plasma levels of malondialdehyde before and after treatment as a measurement of DNA oxidation, RNA oxidation, and lipid peroxidation, respectively., Results: Clarithromycin significantly increased urinary excretion of 8-oxodG by 22.0% (95% confidence interval (CI): 3.6-40.4%) and 8-oxoGuo by 14.9% (95% CI: 3.7-26.1%). Further, we demonstrated that trimethoprim significantly lowered urinary excretion of 8-oxodG by 21.7% (95% CI: 5.8-37.6%), but did not influence urinary excretion of 8-oxoGuo. Penicillin V did not influence urinary excretion of 8-oxodG or 8-oxoGuo. None of the antibiotic drugs influenced plasma levels of malondialdehyde., Conclusion: Clarithromycin significantly increases oxidative nucleic acid modifications. Increased oxidative modifications might explain some of clarithromycin's known adverse reactions. Trimethoprim significantly lowers DNA oxidation but not RNA oxidation. Penicillin V had no effect on oxidative nucleic acid modifications., (© 2017 The British Pharmacological Society.)

There is an urgent need to develop new drug treatment strategies to control the global spread of drug-sensitive and multidrug-resistant Mycobacterium tuberculosis (M. tuberculosis). The ß-lactam class of antibiotics is among the safest and most widely prescribed antibiotics, but they are not effective against M. tuberculosis due to intrinsic resistance. This study shows that 2-aminoimidazole (2-AI)-based small molecules potentiate ß-lactam antibiotics against M. tuberculosis. Active 2-AI compounds significantly reduced the minimal inhibitory and bactericidal concentrations of ß-lactams by increasing M. tuberculosis cell envelope permeability and decreasing protein secretion including ß-lactamase. Metabolic labeling and transcriptional profiling experiments revealed that 2-AI compounds impair mycolic acid biosynthesis, export and linkage to the mycobacterial envelope, counteracting an important defense mechanism reducing permeability to external agents. Additionally, other important constituents of the M. tuberculosis outer membrane including sulfolipid-1 and polyacyltrehalose were also less abundant in 2-AI treated bacilli. As a consequence of 2-AI treatment, M. tuberculosis displayed increased sensitivity to SDS, increased permeability to nucleic acid staining dyes, and rapid binding of cell wall targeting antibiotics. Transcriptional profiling analysis further confirmed that 2-AI induces transcriptional regulators associated with cell envelope stress. 2-AI based small molecules potentiate the antimicrobial activity of ß-lactams by a mechanism that is distinct from specific inhibitors of ß-lactamase activity and therefore may have value as an adjunctive anti-TB treatment.

The purpose of the study was to evaluate how use of antibiotics precedes the presence of ESBL-producing E.coli in general practice. The authors performed a triple-case-control study where three case groups were individually compared to a single control group of uninfected individuals. Urine samples were prospectively collected and retrospective statistical analyses were done. This study included 98 cases with urinary tract infection (UTI) caused by ESBL-producing E. coli, 174 with antibiotic-resistant (non-ESBL) E. coli, 177 with susceptible E. coli and 200 with culture negative urine samples. Case groups had significantly higher use of antibiotics than the control group within 30 days before infection (p < 0.0001). The ESBL group had significantly more hospital admissions than the other case groups (p < 0.05). Hospital admission was an independent risk factor for community onset UTI by ESBL-producing E. coli. Exposure to antibiotics was a risk factor for UTI with E. coli, while prior antibiotic usage was not an indisputable predictor for infection with ESBL-producing E.coli in general practice.

Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides - which are the most frequent cause of adverse drug reactions - were co-incubated with THP-1, MUTZ-LC, or primary monocyte-derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1β, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Two well-known antibiotic heterocycles, the 'quinolone' nalidixic acid and the β-lactam penicillin V, active at different levels of the bacterial growth process, have been attached via an ether-ester junction to the p-tert-butylcalix[4]arene lower rim, in alternate position. The resulting hydrophobic molecular drug-organisers were fully characterized, and evaluated over two Gram negative and three Gram positive reference strains, using disk diffusion assays with disks impregnated with solution of title compound in pure DMSO. An interesting activity was observed over Staphylococcus aureus ATCC 25923 with the dis-symmetrical podand incorporating one penicillin and one nalidixic ester moieties., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Inhibitive and adsorption properties of Penicillin G, Amoxicillin and Penicillin V potassium were studied using gravimetric, gasometric and quantum chemical methods. The results obtained indicate that these compounds are good adsorption inhibitors for the corrosion of mild steel in HCl solution. The adsorption of the inhibitors on mild steel surface is spontaneous, exothermic and supports the mechanism of physical adsorption. From DFT results, the sites for nucleophilic attacks in the inhibitors are the carboxylic acid functional group while the sites for electrophilic attacks are in the phenyl ring. There was a strong correlation between theoretical and experimental inhibition efficiencies.

Surface reactions were performed on polypropylene (PP) surfaces to retard the simultaneous growth of Staphylococcus aureus (S. aureus) and Pseudomonas putida (P. putida) bacteria. Microwave plasma reactions in the presence of maleic anhydride (MA) resulted in the formation of acid groups on the surface of PP. Such surfaces were further modified by conducting two parallel reactions: (1) poly(ethylene glycol) (PEG) was attached to COOH groups of the PP surface, followed by penicillin V (PEN) reactions to target S. aureus destruction and (2) diglycidyl PEG was attached, followed by gentamicin (GEN) reactions, to create antimicrobial surfaces targeted at P. putida . Simultaneous gram "+" and gram "-" resistance was obtained by varying the PEN/GEN ratios on such modified PP surfaces, thus providing the controllable degree of gram "+" and gram "-" antimicrobial strength. While spectroscopic analyses revealed chemical attachments of PEN and GEN, the effectiveness against proliferation of S. aureus (Gram +) and P. putida (Gram -) bacteria was determined using liquid culture tests. These studies show for the first time the formation of tunable antimicrobial polypropylene surfaces with controllable strength.

Background: Group A streptococci (Streptococcus pyogenes; GAS) invades human epithelial cell lines. Failure of penicillin to eradicate GAS from the throats of patients, especially those who are GAS "carriers," has been increasingly reported. However, there has been no comprehensive evaluation of how effectively antibiotics that are used to treat GAS enter upper respiratory tract epithelial cells and kill internalized GAS. We examined the viability of ingested, intracellular GAS after epithelial cell exposure to antibiotics commonly recommended for therapy of GAS infections., Methods: A human laryngeal epithelial cell line (HEp-2) was used. Three techniques were used to study antibiotic (penicillin V, erythromycin, azithromycin, cephalothin, and clindamycin) killing of ingested GAS: examination by electron microscopy of ultrathin sections of ingested GAS, qualitative determination of intra-epithelial cell antibiotic, and special stain evaluation of intracellular GAS viability after epithelial cell exposure to antibiotics., Results: GAS survived intracellularly despite exposure of the GAS-containing epithelial cells to penicillin. In contrast, there was killing of ingested GAS after exposure of epithelial cells to either erythromycin or azithromycin. Electron microscopy confirmed a lack of intracellular GAS fragmentation (cell death) after exposure of epithelial cells to penicillin in contrast to obvious GAS fragmentation after epithelial cell exposure to erythromycin or azithromycin. Cephalothin, a cephalosporin, and clindamycin were more effective in killing ingested GAS than was penicillin, but they were less effective than erythromycin or azithromycin., Conclusions: These observations strongly suggest that if the GAS upper respiratory tract carrier state results from intra-epithelial cell GAS survival, the failure of penicillin to kill ingested GAS may be related to a lack of effective penicillin entry into epithelial cells. These unique observations may have clinical implications for understanding GAS respiratory tract carriers and managing GAS infections.

A pooled analysis of two double-blind, multicentre, Phase III studies compared oral telithromycin 800 mg once-daily for 5 days with penicillin V 500 mg three-times-daily or clarithromycin 250 mg twice-daily for 10 days in the treatment of Streptococcus pyogenes (group A beta-haemolytic streptococcus; GABHS) tonsillopharyngitis. Patients aged > or = 13 years with acute GABHS tonsillopharyngitis were randomised to receive telithromycin (n = 430), penicillin (n = 197) or clarithromycin (n = 231). Clinical isolates of S. pyogenes (n = 590) obtained from throat swab samples on study entry were tested for their in-vitro susceptibility to telithromycin, clarithromycin and azithromycin. Telithromycin demonstrated in-vitro activity against the clinical isolates of S. pyogenes (MIC50/90 0.03/0.06 mg/L) higher than clarithromycin or azithromycin (MIC50/90 0.06/0.06 mg/L and 0.12/0.25 mg/L, respectively), including erythromycin-resistant strains. At the post-therapy/test of cure (TOC) visit (days 16-23), satisfactory bacteriological outcome was demonstrated for 88.3% (234/265) and 88.6% (225/254) of telithromycin- and comparator-treated patients, respectively (per-protocol population). Overall, GABHS eradication rates were 88.7% (235/265) for telithromycin and 89.0% (226/254) for comparators. The clinical cure rates at the post-therapy/TOC visit were 93.6% (248/265) and 90.9% (220/242) for telithromycin and pooled comparators, respectively. Telithromycin was generally well-tolerated. Most adverse events considered to be possibly related to study medication were gastrointestinal and of mild intensity. Discontinuations as a result of adverse events were few in both treatment groups. In conclusion, telithromycin 800 mg once-daily for 5 days was as effective as penicillin V or clarithromycin for 10 days in the treatment of GABHS tonsillopharyngitis.

The clinical efficacy, safety and bacteriological eradication of Group A beta-haemolytic streptococci (GABHS) from the throat was studied after treatment of streptococcal tonsillopharyngitis with three commonly used oral antibiotics in a prospective, open labelled, comparative, randomised trial of 265 evaluable patients seen in one centre. All three antibiotics were administered in the recommended doses; penicillin V q8 hourly and clarithromycin q12 hourly were given for 10 days and cefprozil q12 hourly for 5 days. Clinical results and adverse events were similar for all three antibiotics used, with a prompt clinical outcome of >95%. Cefprozil had the best bacteriological eradication rate (failed to eradicate: 13.2, 15.1, 2.3; relapses: 13.2, 11.4, 5.7%, for penicillin, clarithromycin and cefprozil, respectively). Oral penicillin remains a clinically effective and safe antibiotic for the treatment of streptococcal pharyngitis. However, compliance and convenience for parents and children when they are asked to follow a 10 days course, especially when the patient has improved from the second or third day, together with the high incidence of bacteriological eradication failures, is an issue.

Starburst PAMAM dendrimers are potential carriers for drug delivery due to their unique structure. Drug-delivery scaffolds were designed and built up based on the polyethylene glycolpolyamidoamine (PEG-PAMAM) star polymer. Penicillin V was used as a model carboxylic group containing drug to conjugate with full- and half-generation PAMAM dendrimers. G2.5 PAMAM (with 32 carboxylic groups on the surface) dendrimers and G3.0 (with 32 primary amine groups on the surface) were typically chosen. There are two strategies given in the paper where a drug carrying a carboxylic group (e.g. penicillin V) was coupled to star polymer via amide and ester bonds, respectively. FT-IR, UV-Vis and 1H-NMR were used to characterize the intermediates and drug-star polymer conjugates. A single-strain bacterium, Staphylococcus aureus, was grown up for penicillin-conjugated PEG-PAMAM (G3.0) star polymer activity test. The result verified the bioavailability of modified penicillin after the ester bond was cleaved.

Objective: This study compared a short-course of clarithromycin with a standard course of penicillin V in patients with tonsillopharyngitis caused by Streptococcus pyogenes., Research Design and Methods: A total of 539 patients, aged 12-75 years, were randomized to receive either clarithromycin extended-release (ER) 500 mg once daily for 5 days or penicillin V 500 mg three times daily for 10 days in this multicenter, double-blind, parallel-group trial. Eligibility required a positive antigen test for group A beta-hemolytic streptococcus (GABHS) followed by confirmatory culture., Main Outcome Measures: Bacteriological and clinical assessments were conducted at each study visit (visit 1: study day 1; visit 2: study day 3; visit 3: study days 8-12; visit 4: study days 13-20; and visit 5: study days 40-50)., Results: At the test-of-cure visit (visit 3 for clarithromycin ER patients and visit 4 for penicillin V patients) in per-protocol patients, 5 days of clarithromycin ER was comparable to 10 days of penicillin V in eradicating S. pyogenes (89% (157/177) vs 90% (139/154) respectively; 95% CI for difference (-8.2, 5.1)). Bacterial eradication was sustained in both treatment groups at the follow-up visit (88% (135/153) vs 91% (112/123) respectively; 95% CI for difference (-10.0, 4.4)). Clinical cure was achieved in > or = 94% of patients in each treatment group. The most commonly reported study drug-related adverse events (< or = 3% in either treatment group) were abdominal pain, diarrhea, dyspepsia and nausea., Conclusion: Clarithromycin ER 500 mg once daily for 5 days is equally effective as penicillin V 500 mg three times daily for 10 days in the treatment of adolescent and adult patients with streptococcal tonsillopharyngitis.

Antibiotics to treat endodontic infections are routinely prescribed based on previously published susceptibility tests. There is increased concern that bacteria have increased resistance to the currently recommended antibiotics. The purpose of this investigation was to perform antibiotic susceptibility tests on a panel of bacteria recently isolated from endodontic infections. The bacteria in this study were aseptically aspirated with a needle from endodontic abscesses, cultivated, and identified at the species level. Each of the 98 species of bacteria was tested for antibiotic susceptibility to a panel of six antibiotics using the Etest. The antibiotics were penicillin V, amoxicillin, amoxicillin + clavulanic acid, clindamycin, metronidazole, and clarithromycin. The percentages of susceptibility for the 98 species were penicillin V: 83/98 (85%), amoxicillin: 89/98 (91%), amoxicillin + clavulanic acid: 98/98 (100%), clindamycin: 94/98 (96%), and metronidazole: 44/98 (45%). Metronidazole had the greatest amount of bacterial resistance; however, if it is used in combination with penicillin V or amoxicillin, susceptibility of the combination with penicillin V or amoxicillin increased to 93% and 99%, respectively. Clarithromycin seems to have efficacy, but it is still considered an antibiotic under investigation because the minimum inhibitory concentration has not been established.

Objective: The purpose of the study was to identify the bacterial composition of the microbiota from acute endodontic abscesses/cellulitis and their antimicrobial susceptibilities., Study Design: Purulence from 17 patients with acute endodontic abscesses/cellulitis was obtained by needle aspiration and processed under anaerobic conditions. Bacteria were isolated and identified by biochemical or molecular methods. The antimicrobial susceptibility of isolated bacteria was determined by using the Etest., Results: All 17 aspirates contained a mix of microorganisms. A total of 127 strains of bacteria were isolated. Of 127 strains, 80 strains were anaerobes and 47 strains were aerobes. The mean number of strains per sample was 7.5 (range, 3 to 13). The average number of viable bacteria was 6.37 x 10(7) (range, 10(4) to 10(8)) colony-forming units/mL. Strict anaerobes and microaerophiles were the dominant bacteria in 82% (14 of 17) of the cases. The genera of bacteria most frequently encountered were Prevotella and Streptococcus. Prevotella and Peptostreptococcus were frequently found to dominate the mixture. The combination of Prevotella and Streptococcus was found in 53% (9 of 17). The previously reported uncultured Prevotella clone PUS9.180 was frequently identified. The percentage of bacteria susceptible/intermediate for each antibiotic in this study was penicillin V, 81% (95 of 118); metronidazole, 88% (51 of 58); amoxicillin, 85% (100 of 118); amoxicillin + clavulanic acid, 100% (118 of 118); and clindamycin, 89% (105 of 118)., Conclusions: The present results confirm the existence of mixed infection with the predominance of anaerobic bacteria in acute endodontic abscesses/cellulitis. The frequency of uncultured Prevotella clone PUS9.180 suggests the possible key role of this Prevotella species in acute endodontic infections. Penicillin V still possesses antimicrobial activity against the majority of bacteria isolated from acute endodontic infections. However, if penicillin V therapy has failed to be effective, the combination of penicillin V with metronidazole or amoxicillin with clavulanic acid is recommended. Switching to clindamycin is another good alternative.

The NCCLS agar dilution method and Etest are currently accepted methods for susceptibility testing of Neisseria meningitidis to penicillin. We determined the MIC of penicillin V and penicillin G by both the agar dilution method and Etest using 43 strains of N. meningitidis. Although results for reference strains were within the accepted quality control range of penicillin MICs for both drugs, differences of two to three dilutions were seen between the two antibiotics with both methods. Penicillin V results cannot correctly predict the susceptibility to penicillin G for N. meningitidis if penicillin G breakpoints are used for penicillin V. However, adjusting the penicillin V breakpoints two dilutions higher (i.e., S < or = 0.25 and R > or = 8 microg/ml), concordance could be achieved for susceptibility categorization by the two compounds. An agreement of 98% +/- 1 dilution was obtained between Etest and the reference method when using penicillin G strips. We conclude that Etest with penicillin G strips is a convenient and reliable alternative method for determining the MICs of penicillin for N. meningitidis.

Objective: To compare a 3-day azithromycin vs. a 10-day penicillin V regimen for treatment of acute group A streptococcal (GAS) pharyngitis in children and to determine whether viral infection and/or pharyngeal GAS carriage in patients and adult contacts affect clinical and bacteriologic efficacy., Methods: This multicenter, randomized, comparative, open label study compared 3-day, once daily 10 mg/kg azithromycin oral suspension with a 10-day regimen of 100,000 IU/kg/day penicillin V oral suspension in three divided doses in children with acute GAS pharyngitis. Clinical and bacteriologic efficacy and tolerability of the antibiotics were evaluated. Recurrence of symptoms and infection was monitored for 6 months., Results: In total, 292 children (age range, 2 to 12 years) received at least one dose of study medication. Clinical success (cure/improvement) with either antibiotic was similar at the end of therapy (Day 14; azithromycin, 95%; penicillin V, 97%) and at Day 28 (azithromycin, 94%; penicillin V, 95%). Bacteriologic eradication was significantly less with azithromycin than with penicillin V at Day 14 (azithromycin, 38%; penicillin V, 81%; P < 0.001) and at Day 28 (azithromycin, 31%; penicillin V, 68%; P < 0.001). There was no associated increase in GAS-related sequelae. The lower incidence of bacteriologic eradication with azithromycin was not the result of possible concomitant viral infections in the patients, GAS carriage in one parent/guardian or any reduced susceptibility in pretreatment GAS isolates. Both antibiotics were equally well-tolerated., Conclusions: Treatment with 3-day, once daily 10 mg/kg azithromycin for GAS pharyngitis is associated with similar high levels of clinical efficacy, but lower levels of bacteriologic eradication, than with 10-day 100,000 IU/kg/day penicillin V.

Background: Three-day, 10 mg/kg/day azithromycin (AZM) studies in pediatric acute group A streptococcal tonsillopharyngitis have shown contradictory bacteriologic results. This study investigates the efficacy and tolerability of two dosages of 3-day azithromycin (20 mg/kg/day and 10 mg/kg/day) compared with 10-day penicillin V., Methods: This was a prospective, comparative, randomized, multicenter trial. Children were scheduled to return for visits at 14 days (main end point) and 1 month after the onset of treatment for clinical and bacteriologic assessment. Molecular tools were used to compare pre- and posttreatment group A beta-hemolytic Streptococcus (GABHS) isolates., Results: Between November, 1997, and July, 1998, 501 patients (169 AZM 10 mg, 165 AZM 20 mg, 167 penicillin V) between 2 and 12 years old were enrolled; 500 were assessable for safety, 469 for intent to treat analysis and 420 for efficacy in the per protocol analysis. Before treatment 25 (7.9%) of 315 GABHS stains isolated from patients receiving AZM were resistant to this compound. On Day 14 pretreatment GABHS were eradicated from 78 (57.8%) of the 135 children receiving the AZM 10 mg regimen, 131 (94.2%) of the 139 receiving AZM 20 mg and 123 (84.2%) of the 146 taking penicillin. One month after the outset of treatment, bacteriologic relapses were observed in 40.5% (n = 30) of the children receiving AZM 10 mg, 14.8% (n = 18) of children taking AZM 20 mg and 13.2% (n = 15) of those treated with penicillin V. AZM 20 mg/kg/day was statistically superior to AZM 10 mg/kg/day microbiologically on Day 14 (P = 0.0001) and Day 30 (P = 0.0001) and clinically on Day 14 (P = 0.0035). AZM 20 mg/kg/day was statistically equivalent both microbiologically and clinically to standard therapy with penicillin V at all endpoints. The incidence of treatment-related adverse events was similar in the two azithromycin groups [AZM 10 mg, 31 of 169 (18.3%); AZM 20 mg, 37 of 164 (23%)] but significantly higher than those observed in the penicillin V group [5 of 166 (3%); P < 0.0001]. Most treatment-related adverse events were gastrointestinal and of mild-to-moderate severity. Fourteen patients withdrew from the trial because of adverse events (1 in the penicillin V group, 7 in the AZM 10 mg group and 6 in the AZM 20 mg group)., Conclusion: This is the first study to demonstrate a daily dose-dependent difference in microbiologic efficacy of a regimen; 3-day AZM 20 mg/kg/day is a more effective regimen than 3-day AZM 10 mg/kg/day for pediatric GABHS tonsillopharyngitis.

Objective: To evaluate the efficacy of oral penicillin V and intramuscular benzathine penicillin G (BPG) in eradicating group A streptococci from the upper respiratory tract., Methodology: Two randomized, single-blind, multicenter antibiotic efficacy trials in children using recommended doses of either oral penicillin V or intramuscular BPG for treatment of acute-onset pharyngitis associated with isolation of group A streptococci were conducted. Throat examinations and cultures were obtained at enrollment and on days 5 to 8, 10 to 14, and 29 to 31., Results: Thirty-five percent of 284 evaluable patients treated with oral penicillin V and 37% of BPG-treated patients were microbiologic treatment failures at either 10 to 14 or 29 to 31 days., Conclusions: Although these findings do not provide sufficient evidence to change current treatment recommendations or public health policy, important questions are raised about currently recommended penicillin doses, about the role of the carrier state, and possibly about adequate bioavailability of intramuscular BPG. These findings require confirmation.

This paper presents a novel microphysiometer for simultaneous measurements of several extracellular ions concentrations in living cells based on MLAPS (multi-light addressable potentiometric sensor). In the microphysiometer, different sensitive membranes are illuminated in parallel with n light sources at different frequencies, the response amplitudes of each frequency component can be measured on-line by parallel processing algorithm. By the experiments, we can analyze the relations of the extracellular environmental H(+), Na(+), K(+), Ca(2+) under the effects of western medicines (dilantin, phenobarbital sodium, penicillin sodium) and Chinese drugs (scutellaria, medlar, hemlock parsley), and estimate the effects of several drugs. As the novel microphysiometer works under regular cell culture conditions, cells can be repeatedly simulated with drugs to complete dose-response curve within a few hours. With the detection of a general parameter (extruded protons and ions), the system can be used to monitor the real-time process of the cells' metabolism, observe the functional responses of different kinds of membrane-bound receptors, evaluate the drugs.

Objective: Previous studies have shown that acute otitis media alters modeling dynamics in bone tissue structures surrounding the middle ear cavity. Initial resorption is followed by formative activity, which is seen as massive osteoneogenesis. However, neither resorptive nor formative activity occurs in the otic capsule, supporting the theory on existence of a perilymphatic barrier of specialized bone., Study Design: To investigate the effect of penicillin administration on the pathological bone modeling in acute otitis media, we employed a rat model of acute pneumococcal otitis media., Methods: Five rats were sacrificed on postinoculation days 4, 8, 16, 90, and 180, preceded by oral administration of penicillin V 100 mg/kg per day, initiated on day 2 and lasting 5 (2) days. Using a light microscope, bone histomorphology was registered and the thickness measured in four well-defined localities, followed by comparison with a previous study of untreated animals., Results: Measured bone thickness was unaffected by treatment on day 4, but significantly reduced in two localities on day 8 and in all localities on following days of sacrifice. Bone cytomorphology and histomorphology were otherwise unaffected by penicillin administration., Conclusion: Penicillin reduces new bone formation in acute otitis media, leaving other features of histomorphology unchanged.

The activation of CD4+ T lymphocytes upon Ag stimulation plays a critical role in adverse immune responses including drug-specific hypersensitivity reactions. We examined the modulation of T cell phenotype induced by hapten-specific stimulation using the model of beta-lactam antibiotics such as penicillin G (Pen G), Pen V, and ampicillin (Amp). When PBMC of donors suffering from hypersensitivity reactions against beta-lactams were stimulated in vitro with different doses of Pen G, a preferential expansion of IL-4-producing TCR alphabeta+ cells was detected. A panel of T cell clones was then prepared from Pen G-specific lines after two cycles of restimulation with the hapten. For the majority of these clones, we found that high doses of Pen G induced optimal IL-4 secretion, whereas the amount of IFN-gamma secreted was inversely correlated with the dose of Pen G, thus leading to a hapten-inducible shift of the functional phenotypes for some of the clones. Finally, Pen V and Amp were used to modulate different Ag-induced immune responses. We found that Amp had no influence on the cytokine pattern induced by specific Ag or mitogens. In contrast, Pen V inhibited the secretion of IFN-gamma, but not IL-4, most likely by Ag-independent mechanisms. This last finding may open new applications for immune intervention in those diseases in which polarized Th1 responses are involved in the development of the pathology.

Tonsillar microbial flora was studied in cultures of tonsillar core specimens from 34 patients tonsillectomized due to recurrent group A streptococcal pharyngotonsillitis (n = 17) or sleep apnoea (n = 17). Patients in the sleep apnoea subgroup, who had no history of recurrent tonsillitis and manifested no tonsillar hypertrophy at ENT examination, served as controls. Tonsillar core specimens were cultured for semi-quantitative estimation of growth of aerobic, anaerobic and facultative organisms. The recurrent tonsillitis and apnoea subgroups did not differ significantly in the mean number of isolates per patient, either of aerobic spp. (3.8 vs. 4.3) or anaerobic spp. (5.2 vs. 4.7). Nor did the two subgroups differ significantly in the proportion of patients whose specimens manifested beta-lactamase producers (71% vs. 59%), in the isolation frequency of viridans (alpha) streptococci, or in the occurrence of semi-quantitative growth estimates of 3-4+ for aerobic, anaerobic or beta-lactamase-producing spp. Thus, the study provided no support for the hypothesis that inactivation of penicillin V by beta-lactamase-producing bacteria in oral or throat flora, or the eradication of viridans streptococci with their GAS-inhibitory capacity, is an important factor with regard to recurrent group A streptococcal tonsillitis. Other possible explanations, such as poor antibiotic penetration at the site of infection, are discussed.

Fibrous middle ear adhesions are occasionally encountered in middle ear surgery and may cause a hearing impairment. Although usually associated with chronic otitis media, adhesions are also found following a single episode of experimental acute suppurative otitis media, suggesting a pathogenesis based on the inflammatory process engaging acute infection. In a well-established rat model of pneumococcal acute otitis media, we report on the effect of penicillin V on formation of fibrous middle ear adhesions. Previous studies have shown marked impact of penicillin on mucosal goblet cell density and other histopathologic features. Number, anatomic localization, and histopathologic morphology of adhesions were assessed in a longitudinal study of 25 normal, 25 untreated, and 25 treated rats. Although penicillin administration induced a slight tendency toward fewer ears with adhesions and fewer adhesions per ear, these changes were nonsignificant. Histomorphology and the general pattern of anatomic localization of adhesions were unaffected by penicillin administration. We conclude that administration of penicillin has an inconspicuous effect on the formation of fibrous adhesions in experimental acute otitis media caused by Streptococcus pneumoniae.

The ecological effects on the commensal microflora in saliva and stool samples were studied during administration of two commonly used antibiotics: cefadroxil 500 mg b.i.d. for 10 days and phenoxymethylpenicillin 1 g b.i.d. for 10 days. Twenty healthy volunteers participated in the study. In the oropharyngeal microflora the aerobic microflora was significantly suppressed during administration of cefadroxil while no significant changes were noticed in the anaerobic microflora. Administration of phenoxymethylpenicillin caused a strong decrease in the number of viridans streptococci and an overgrowth of Neisseria cocci. The total numbers of anaerobic oropharyngeal microorganisms were suppressed during phenoxymethylpenicillin administration. In the intestinal microflora the variation in numbers of aerobic and anaerobic microorganisms was minor in both groups. The microflora became normalised 2 weeks after withdrawal of the drugs. It was concluded that peroral administration of cefadroxil to healthy volunteers resulted in minor ecological disturbances in the oropharyngeal and intestinal microflora, which were in the same range as for phenoxymethylpenicillin.

Background: The effect of antibiotic therapy in sore throat is questionable and this dilemma has been complicated by the emergence of multiple resistant strains of micro-organisms., Aim: A randomized double-blind placebo-controlled clinical trial was undertaken in patients aged 4-60 years to assess the efficacy of penicillin V on the clinical course and bacteriological response in patients with sore throat in general practice., Method: Two hundred and thirty-nine patients presenting with an acute sore throat to 37 general practices in the Netherlands who were clinically suspected of group A beta-haemolytic streptococci (GABHS) were randomized for treatment with penicillin V (n = 121) or placebo (n = 118). Resolution of sore throat, fever and return to daily activities were evaluated by the general practitioner 2 days after the start of treatment and by the patients keeping a diary for 7 days. The result of throat culture after 2 days was evaluated., Results: A difference in resolution of sore throat was present after 2 days in all patients, but was a result of GABHS-positive patients (n = 111; 46%) in favour of those randomized for penicillin V (adjusted odds ratio 5.3; 95% CI 1.9-15.1). An effect in the course of fever was also seen in GABHS-positive patients (adjusted odds ratio 5.3; 95% CI 1.02-27.7). A difference of 1-2 days was seen in clinical recovery. No difference was found in daily activities between the treatment groups. After 2 days, 4% of the penicillin-treated patients harboured GABHS compared with 75% of the placebo group., Conclusion: Only GABHS-positive patients benefit from penicillin V in their clinical cure in the first few days. Therefore, rapid testing is necessary. Treatment may be beneficial with regard to the clinical course, but it is not necessary.

A phenoxymethylpenicillin amidohydrolase which hydrolyses phenoxymethylpenicillin to 6-aminopenicillanic acid (6-APA) has been isolated from two species of Penicillium chrysogenum. The amidohydrolase had a molecular mass of approx. 42 kDa. Its activity with benzylpenicillin as substrate was only 1.5% of that with phenoxymethylpenicillin and it was inhibited by its products. No penicillin formation from 6-APA and phenoxyacetyl or phenylacetyl coenzyme A was observed. The enzyme is thus distinct from the phenylacetyl coenzyme A:6-APA acyltransferase, which also has amidohydrolase activity and is involved in the final stages of the biosynthesis of penicillins.

We investigated the enzymatic acylation of penicillin-binding protein 2a (PBP 2a) from methicillin-resistant Staphylococcus aureus by beta-lactams. Using a purified, soluble form of the protein (PBP 2a'), we observed beta-lactam-induced in vitro precipitation following first-order kinetics with respect to protein concentration. We used electrospray mass ionization spectrometry to show that the protein precipitate predominantly contained PBP 2a', with the beta-lactam bound to it in a 1:1 molar ratio. Using nitrocefin, a chromogenic beta-lactam, we confirmed the correlation between PBP 2a' precipitation and its beta-lactam-dependent enzymatic acylation by monitoring the absorbance associated with the precipitate. Finally, dissolving the precipitate in urea, we developed a simple in vitro chromogenic assay to monitor beta-lactam-dependent enzymatic acylation of PBP 2a'. This assay represents a significant improvement over the traditional radioactive penicillin-binding assay.

Arcanobacterium haemolyticum is an infrequent agent of pharyngotonsillitis in children and young adults. Despite the fact that A. haemolyticum is fully sensitive to penicillin in vitro, penicillin treatment failures are frequent. The ability of A. haemolyticum to invade HEp-2 cells and survive intracellulary was investigated. All 12 strains tested, of which 10 were isolated from patients with pharyngotonsillitis, and 2 were reference strains, were internalized by the HEp-2 cells. Four strains tested further, one of the reference strains and 3 of the clinical isolates, proved able to survive intracellularly for 4 days, thus creating intracellular reservoirs of bacteria. It was also shown that erythromycin, an antibiotic known to penetrate well intracellularly, efficiently killed these bacteria.

Acute sore throat is a very common pathology, but should not because of this be considered as banal. In effect, the beta-haemolytic streptococcus A, which is responsible for most of the bacteriological etiologies is not only responsible for distant inflammatory complications, acute articular rheumatism (RAA) and glomerulonephritis, which are re-appearing in the United States, but also a fulminating septicemia and a syndrome of visceral failure that makes a grave prognosis for life. Moreover, today, streptococcus A is one of the factors involved in a series of fatal fasciites and necrosing myosites seen in several European countries. Understanding of these complications gives better definition of the causative immunological mechanisms and particularly the adverse role of the "superantigens" of streptococci in the start of an increase in the responses of immunocompetent cells and pro-inflammatory and prothrombic mediators. Finally, availability now of rapid diagnostic tests with monoclonal antibody techniques confirms the presence of streptococci A in acute sore throat and should help the physician to make an etiological diagnosis that takes into account the clinical signs. Unfortunately, these tests are not widely available in France and are not subject to reimbursement. All these factors justify the introduction of an antibiotherapy targetted at streptococcus A in the context of bacterial sore throat. Oral penicillin V (phenoxymethyl penicillin, Oracilline) is always the reference, with an excellent anti-bacterial and clinical activity and without risk of production of strains of streptococcus that are of reduced sensitivity or resistant.(ABSTRACT TRUNCATED AT 250 WORDS)

The choice of antibiotic therapy for sore throat of bacterial origin must be directed against the beta-haemolytic streptococcus A, or more rarely C and G. Recent bacteriological data confirm the raised and constant antibacterial activity in vitro of penicillins V and G, with minimal inhibitory concentrations (CMI) as low as 0.01 mg/ml. Until now, there have been no resistant or reduced sensitivity strains reported. Those strains reported as "tolerant" to penicillin are not correlated with therapeutic checks. As for strains of "intermediate sensitivity" to penicillin, these should be attributed to effects of the diffusion techniques. In contrast, in France now, 8% of strains of streptococcus A are resistant to macrolides and 60% to tetracyclines. Finally, new data show that the different selective powers of beta-lactamines, especially cephalosporins, introduce risks of modification of the oro-pharingeal ecology, linked in part with transfer of genetic material between commensal streptococci of reduced sensitivity to beta-lactamines to sensitive pneumococci. All these data emphasize the importance of an antibiotic therapy that is directed to streptococcus A, with a strong and constant bactericidal activity, without risk of selection or appearance of strains of resistant streptococcus A, and that will not disturb the long term bacterial ecology of the oro-pharynx. Now, in 1994 phenoxymethylpenicillin, Oracilline, penicillin V has the place of reference in the treatment of bacterial acute sore throat.

The beta-haemolytic streptococcus A, which is responsible for almost all bacterial sore throats in children and young adults, is the target for the first antibiotic treatment. What is really at stake for the treatment is to prevent the serious complications linked with this germ, acute articular rheumatism (RAA) and glomerulonephritis. The recurrence of RAA seen in the United States from 1985, has started many investigations as much for epidemiology as for therapy. Some authors have questioned the treatment with penicillin because of the rise in numbers of carriers of streptococcus A after treatment. They have suggested the use of compounds with a greater spectrum of activity. However, work in the international literature re-states the benefits of a targetted antibio-therapy in this context. Is it appropriate to use a wide spectrum antibiotic to treat an infection of monobacterial target, taking into account the bacteriological and clinical efficacy of penicillin, the only available treatment that has shown its capacity to prevent RAA, with a treatment length of 10 days and which seems to be constant with time? Because of this, faced with the ecological risks of a multi-use of wide range compounds, with a treatment that has not been validated in France, phenoxymethylpenicillin, Oracilline, penicillin V, the antibiotic targetted to sore throat and the streptococcal risk, is correct now for 1994.

A new reagent for the detection of penicillin-binding proteins (PBPs) was developed. An N-hydroxysuccinimide ester of biotin was used to tag beta-lactam antibiotics with free side chain amino groups such as ampicillin (BIO-AMP), 6-aminopenicillanic acid (BIO-APA), and 7-aminocephalosporanic acid (BIO-ACA). Bacterial PBPs from cells or isolated cytoplasmic membranes of Escherichia coli, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae were labeled with BIO-AMP, subjected to electrophoresis on sodium dodecyl sulfate (SDS)-polyacrylamide gels, and transferred onto nitrocellulose membranes. Electrophoretic PBP profiles were detected on blots, using colorimetric or chemiluminescence systems, on the basis of the interaction of BIO-AMP-PBP complexes and a streptavidin-peroxidase conjugate. The chemiluminescent reaction permitted a high sensitivity of detection, and PBP profiles could be determined within seconds. All PBP profiles were similar to those obtained with a traditional PBP labeling technique with 125I-labeled penicillin V, except that an additional unidentified PBP (approximately 55,000 Da) was labeled with BIO-AMP in E. coli and H. influenzae. Differences in the intensities of labeling for specific PBPs were observed between the chemiluminescent and radioactive labeling agents and were attributed to the differences in their affinities for PBPs. Similarly, BIO-AMP, BIO-APA, and BIO-ACA produced different PBP profiles. We also investigated the use of BIO-AMP in PBP purification. BIO-AMP-PBP complexes from a mixture of H. influenzae proteins were allowed to bind to avidin immobilized on an agarose support in a microcentrifuge tube. After several washes in the presence of salts, PBPs were eluted by boiling and treatment with SDS. The eluted proteins were separated by electrophoresis on SDS-polyacrylamide gels, and biotinylated proteins were identified on blots by a chemiluminescence reaction. Biotinylation of beta-lactams is rapid, safe, and inexpensive. Our results demonstrate the feasibility of using biotinylated beta-lactams as nonradioactive reagents for the study of PBPs and for the purification of these proteins.

The susceptibility to penicillin of 6 prevalent pneumococcal types isolated from nasopharynx in 1992 was compared with that of corresponding types from 1980-82. The 6 types or groups, 6, 9, 14, 15, 19 and 23, constituted 78% of consecutive isolates. 19/204 isolates in 1992 were intermediately resistant (MIC 0.12-1.0 mg/l) in comparison with 1/194 from 1980-82 (p < 0.001). Resistant strains (MIC > or = 2 mg/l) were not found. Of group 15, no fewer than 10/31 isolates were intermediately resistant, which may support the clonal origin and spread of penicillin-resistant pneumococci. At least 5.0% of nasopharyngeal isolates are now intermediately resistant to penicillin. This figure is substantially higher than the 2% earlier reported in Sweden.

In a randomised, operator-blind, comparative clinical trial, the efficacy of co-amoxiclav (250 mg amoxycillin plus 125 mg clavulanic acid, eight-hourly) was compared to that of penicillin V (250 mg phenoxymethylpenicillin, six-hourly) in the treatment of acute dentoalveolar abscess. In each case surgical drainage was established at the time of initial presentation by incision of any soft tissue swelling, accompanied by either extraction of the tooth or extirpation of the pulp as indicated clinically. Each patient recorded the severity of their pain and swelling at eight-hourly intervals using graduated scales. Clinical review was performed after 1, 2 and 5 days of treatment, at which time sublingual temperature was recorded and the presence of cervical lymphadenopathy determined. A total of 79 patients were clinically assessable on Day 5 (co-amoxiclav, n = 41; penicillin V, n = 38). The two groups were comparable for sex, age, presenting features and microbiology. Penicillin-resistant organisms were isolated from five patients (co-amoxiclav, n = 3; penicillin V, n = 2). Symptoms improved in all patients following the start of treatment, however those receiving co-amoxiclav recorded a significantly greater decrease in pain during the second (P = 0.026) and third days (P = 0.025). Only one patient reported a significant adverse effect associated with drug therapy, and this was in the penicillin group. Co-amoxiclav was as effective as penicillin therapy.

A random selection of Neisseria meningitidis strains isolated in Sweden in the period 1981-1990 were investigated for plasmid carriage and susceptibility to antimicrobial agents commonly used for treatment and prophylaxis of meningococcal disease. The MICs were determined by the agar dilution method for penicillin V, penicillin G, rifampicin, sulfadiazine, erythromycin and tetracycline. In 13% of the invasive strains the MIC of penicillin V was > or = 0.5 mg/l which may cause concern regarding the usefulness of penicillin V in prophylaxis. In strains isolated from the urogenital tract the MICs of penicillin V and penicillin G were higher than in the invasive strains. In about 82% of the strains isolated in 1987-1988 the MIC of tetracycline was > or = 0.5 mg/l whereas no such strains were found in 1981-1982. Plasmids were found in 2 of 119 invasive strains, in 1 of 50 strains from the respiratory tract and in 1 of 19 strains from the urogenital tract. The plasmid sizes were 1.3, 2.6, 25 and 40 Mda. None of these strains were beta-lactamase producing and no relation to a high degree antibiotic resistance was observed.

The in vitro activity of loracarbef, penicillin V, cefaclor and cefadroxil against log and stationary phase cultures of group A streptococci was compared. MICs and MBCs were determined with the broth dilution method and by a modified agar plate dilution technique where the beta-lactams were inactivated after the MICs were determined allowing inhibited but not killed organisms to grow on further incubation. The MICs of loracarbef and the two cephalosporins were 16-32 times higher than those of penicillin V. In plate dilution the MBC/MIC ratios of all agents were < or = 2 for log phase cultures. With stationary phase cultures, especially in the broth dilution test, the MBC/MIC ratios of loracarbef and the two cephalosporins were > or = 32 for a large number of strains. The phenotype response of stationary phase cultures to beta-lactam antibiotics may not only be related to the physiological status of the streptococci, to the culture conditions and to the beta-lactam under test. The present investigation indicated that the phenotypic response was also an intrinsic property of certain strains.

Background: Streptococcal pharyngitis, caused by group A beta-hemolytic streptococci (GABHS), is among the most common infections seen by primary care physicians. Because the illness can result in rheumatic fever, early eradication of infection is important. Penicillin has been the standard treatment for GABHS pharyngitis for over four decades, but reports of bacteriologic failure with this drug in recent years have led to trials of alternative antimicrobials., Methods: In this investigator-blind, randomized multicenter trial (30 centers), oral clarithromycin, 250 mg twice daily, or oral penicillin VK, 250 mg three times daily, was given to outpatients > or = 12 years old with GABHS pharyngitis as documented by positive cultures for Streptococcus pyogenes and positive rapid immunoassay tests. The clinical and bacteriologic efficacy of clarithromycin was compared with that of penicillin in the 356 evaluable patients. Safety analysis was performed in all patients who had received at least one dose of the study drug (N = 453)., Results: Overall, clinical outcomes were comparable in the two groups. However, more clarithromycin-treated patients than penicillin-treated patients had resolution of sore throat (94% vs 86%, P = .014) and disappearance of pharyngeal erythema and exudate (89% vs 82%, P = .05). Bacteriologic cure rates were higher in clarithromycin-treated patients (95% vs 87%, P = .009). No serious adverse events were observed in either group., Conclusions: This study suggests that clarithromycin twice daily is as effective and as well tolerated as penicillin in the treatment of streptococcal pharyngitis.

There is good background evidence to suggest that essential fatty acids and their eicosanoid derivatives may play a role in schizophrenia and in with tardive dyskinesia. Trials involving treatment with essential fatty acids, or eicosanoids or drugs which stimulate eicosanoid synthesis have shown modestly promising results. Particularly favourable outcomes in both schizophrenia and tardive dyskinesia were associated with combined treatment using essential fatty acids and nutritional supplements.

The susceptibility of 106 oral bacteria to meropenem, a new carbapenem antimicrobial, penicillin V, tetracycline and metronidazole was assessed by an agar dilution method. Meropenem was the most effective of the antimicrobials, with all strains tested being inhibited at < or = 1 mg/l. A number of strains were resistant to penicillin V, particularly Bacteroides gracilis, and tetracycline resistance was widespread amongst the streptococci tested. Metronidazole was extremely effective against obligate anaerobes. The results of this study suggest that meropenem has potential for use in the treatment of serious head and neck infections.

Streptococcus pneumoniae has a prominent role in infectious bronchopulmonary diseases. This organism is normally sensitive to a vast number of antibiotics. However, in recent years, acquired resistance against tetracyclines, macrolides, and, more recently, penicillins, has emerged. Since 1987, there is indeed a regular increase in the frequency of strains that have a lower sensitivity to penicillin G (less than 1% before 1986; 12% in 1990). However, this percentage of strains with a lower sensitivity is much more important among non-invasive as opposed to invasive organisms that are isolated from blood, pleural and spinal fluid cultures (3.3% in 1990). Among strains with abnormal sensitivity to penicillin G, there are very selective serotypes or serogroups: 4 types or groups (23, 19, 6 and 14) represent 80% of these strains. More than 80% of the strains of MIC greater than 2 mg/l are among only one stereotype, 23F. This abnormal sensitivity to penicillin G implies a modification of sensitivity to all beta-lactams, but MIC increase to a variable extent depending on the antiinfectious agent. The most efficient agents against strains of lower sensitivity are amoxicillin, imipenem and parenteral third generation cephalosporins. On the other hand, for all oral first, second and third generation cephalosporins, MIC increase to levels for which seric levels that are reached hardly demonstrate convincing efficiency. Even if resistance levels are less marked as shown by strains isolated from pulmonary infections as compared to what is seen in ENT, the trend in the development of abnormal sensitivity of pneumococci to beta-lactam agents urges the clinician to take into account these data in the therapeutic coverage of bronchopulmonary infections.

The effects of phenoxymethylpenicillin on the bacterial flora of the vagina were investigated in 6 women who fulfilled the criteria of 'normality': predominance of lactobacilli, and absence of Enterobacteriaceae and fungi. Fourteen healthy women were enrolled and followed longitudinally; 8 of these were subsequently excluded because of divergence from normality. Following penicillin treatment, Gram-negative rods appeared in 4 of the remaining 6 women, and in 1 subject heavy growth of Candida albicans resulted. In 5 of the women there was no change in the lactobacillus count and a rise in pH was found in 4 subjects. In 1 woman, lactobacilli disappeared completely and were replaced by Escherichia coli. Concomitantly, high concentrations of endotoxins were found in the vaginal fluid. Treatment with penicillin may interfere with the normal vaginal bacterial flora and provide an environment favorable for Enterobacteriaceae and fungi.

Experiments were designed to test the antibiotic (1-phenoxypropyl)penicillin (propicillin) against a complex microflora of periodontal bacteria. This was accomplished by using a continuously growing mixed culture that was obtained by enrichment of periodontal plaque in human serum. Peptostreptococcus species, Prevotella intermedia, Lactobacillus, catenaforme, and Streptococcus species were dominant members of the enrichment culture. None of the strains isolated from the enrichment culture exhibited detectable beta-lactamase activity. MICs of propicillin for the organisms ranged from 0.1 to 1.2 mg/liter. Propicillin was added to the cultures in single doses that were repeated once or twice at 24-h intervals, that is, after 2.4 volume changes of the culture vessel. Analyses done 24 h after the last addition of propicillin revealed that total cell counts of the culture were hardly affected by 1 mg of propicillin per liter, although some changes in the microbial composition occurred. The relative insusceptibility of the culture might be explained by the low growth rate. Higher concentrations (5, 10, and 50 mg/liter) of the antibiotic caused 10- to 20-fold drops in total cell counts. In these cultures P. intermedia was selectively suppressed to below the detection level, whereas other organisms that were equally susceptible to propicillin were less affected. It was concluded that mixed continuous cultures are a useful tool for studying the effects of antibiotics against the periodontal microbiota.

Sixty-one cultures of Gram-negative anaerobic rods were isolated from deep periodontal pockets of patients with rapidly progressive periodontitis. Isolates were speciated as Bacteroides gingivalis (18 isolates), Bacteroides intermedius (8), Bacteroides oris (1), Bacteroides gracilis (17) and Fusobacterium nucleatum (17). Their susceptibilities, to seven antimicrobial agents, were determined in vitro using a plate dilution technique. Amoxycillin and amoxycillin with clavulanic acid were active against all isolates (MIC less than 1 mg/l) and proved the most effective agents tested. F. nucleatum and B. gracilis showed resistance to erythromycin; F. nucleatum had MIC values ranging from 0.03 mg/l up to 128 mg/l when tested with this, least effective agent. Metronidazole was effective against all isolates except for a few strains of B. gracilis (MIC less than 4 mg/l). Tetracycline hydrochloride and minocycline were active against all isolates except for a few strains of B. gracilis (MIC less than 2 mg/l with both minocycline and tetracycline hydrochloride). Penicillin proved less effective than amoxycillin with regard to inhibition of B. gracilis.

In vivo attachment of beta-haemolytic streptococci Group A (GABHS) to the epithelial cells of the palatine tonsils was determined in 10 patients with current acute tonsillitis (AT-group) and in 10 healthy carriers of GABHS (C-group) according to a method described. Standard bacterial culture revealed growth of GABHS in both groups. In the AT-group, massive attachment of streptococcal chains to the tonsillar epithelium was noted. These chains proved positive for FITC-labelled antibodies against beta-haemolytic streptococci, and were only occasionally found in the C-group. The overall bacterial attachment was significantly greater in the AT-group than in the C-group (p less than 0.001). Phenoxymethylpenicillin treatment caused a dramatic decrease in the number of the attached GABHS bacteria within 24 h. Two weeks after completion of the penicillin treatment one individual in each group was still culture-positive for GABHS.