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The systemic administration of antibiotics in conjunction with mechanical biofilm disruption results in reduced numbers of subgingival periodontal pathogens and improved clinical outcomes. Penicillins, tetracyclines, macrolides, quinolones, and nitroimidazoles were used in laboratory and clinical studies. The current literature was reviewed and studies investigating the effect of antibiotics on periodontal pathogens in biofilm models or in clinical trials were analyzed. While there is only a limited number of in vitro studies, numerous clinical studies reported microbiological outcomes. The combination of amoxicillin and metronidazole seems to provide superior antimicrobial effects when used in biofilm models or in clinical trials. In vitro studies using biofilm models showed that antibiotics alone have only limited effects on the bacterial load in biofilms but might be effective in reducing specific species. These results imply that mechanical biofilm disruption is indicated to allow antibiotics to be effective. Clinical trials also demonstrated that the combination therapy of amoxicillin and metronidazole might result in more superior microbiological effects than amoxicillin or metronidazole alone. The results of clinical studies investigating azithromycin are contrary. While it seems to be appropriate to use in chronic periodontitis (comparable to the new classification: stage 3 or 4, grade B generalized periodontitis), there was no superior effect observed in aggressive periodontitis (comparable to the new classification: stage 3 or 4, grade C generalized periodontitis). Doxycycline cannot be recommended for chronic periodontitis (stage 3 or 4, grade B) patients. Antibiotics as drugs come with side effects. Common adverse effects of antibiotics are opportunistic yeast infection and gastrointestinal complications (e.g., nausea, diarrhea, and colitis). The development of resistance suggests a role for microbiological analysis and antibiotic susceptibility testing in the selection of systemic periodontal antibiotic therapy., (© 2021 S. Karger AG, Basel.)

Aims: The influence of lifestyle-related factors, including smoking and drinking, was evaluated for Helicobacter pylori eradication therapy with vonoprazan or proton pump inhibitors (PPIs)., Methods: Between 2012 and 2016, the medical records of 620 patients receiving H. pylori eradication therapy at Saiseikai Karatsu Hospital were evaluated. Patients had received vonoprazan (20 mg) or PPIs with 200 mg clarithromycin and 750 mg amoxicillin twice daily for 7 days. The influence of lifestyle-related factors on eradication failure was determined in the 2 groups., Results: The eradication rates for vonoprazan and lansoprazole, rabeprazole, and esomeprazole were, respectively, 91.0, 73.8, 72.0, and 84.6%. The vonoprazan eradication rate was significantly higher than those for the PPIs (p < 0.01). Habitual smoking and drinking did not increase eradication failure, and smoking and drinking during the eradication period did not reduce the eradication rate. Metabolic syndrome-related factors including obesity, hypertension, and diabetes mellitus had no negative influence on the eradication rate. Eradication with vonoprazan was more effective compared with that achieved through the use of PPIs., Conclusion: Lifestyle-related factors including smoking and drinking did not exacerbate the H. pylori eradication failure, and vonoprazan was more effective than the PPIs., (© 2018 S. Karger AG, Basel.)

Objective: To investigate the impact of gut microbiota manipulation on fasting and postprandial skeletal muscle metabolism in humans., Methods: 40 obese, insulin-resistant males were randomized to amoxicillin (broad-spectrum antibiotic), vancomycin (narrow-spectrum antibiotic), or placebo (7 days, 1,500 mg/day). Before and after treatment, forearm blood flow and metabolite fluxes across forearm muscle were measured under fasting and postprandial (high-fat mixed-meal) conditions., Results: Vancomycin decreased bacterial diversity, reduced the abundance of Gram-positive Firmicutes, and increased the abundance of Gram-negative Proteobacteria, whereas amoxicillin did not affect microbial composition. Neither vancomycin nor amoxicillin treatment affected fasting and postprandial plasma glucose, free fatty acid (FFA), triacylglycerol (TAG), glycerol, lactate, and insulin concentrations or forearm blood flow. Fasting and postprandial net forearm muscle glucose uptake and the release of lactate were not significantly altered by antibiotic treatment as compared to placebo. Finally, antibiotic treatment did not change fasting and postprandial glycerol, FFA, and TAG fluxes across forearm muscle., Conclusion: The present study demonstrates that short-term antibiotic treatment has no effects on fasting and postprandial forearm substrate metabolism and blood flow in obese men with impaired glucose metabolism. These data suggest that short-term strategies targeting the gut microbiota to improve metabolic health may not be effective in obese humans., (© 2018 The Author(s) Published by S. Karger GmbH, Freiburg.)

Due to increasing bacterial resistance and poor availability of new antibiotics, physicians need to use old, still active antibiotics more frequently. In this study, we focused on clo-foctol and aimed to verify the emergence of clofoctol resistance over time. Additionally, the ability of clofoctol to induce resistance under static and dynamic conditions was evaluated. The minimum inhibitory concentration (MIC) values measured in pathogens isolated from 1990 to 1995 were compared to those isolated from 2017 to 2018. The behaviour of clofoctol is similar to that of amoxicillin, while erythromycin shows a different behaviour with an increase in MIC. A rapid decline in CFUs with complete eradication at 96 and 120 h in the case of clofoctol and amoxicillin, respectively, was observed in a dynamic in vitro model of a pharmacokinetic simulation. Erythromycin provides a reduction in CFUs of approximately one order of magnitude for up to 72 h, and then re-growth is observed. The MIC trend was observed during 5 days of kinetic simulation. The clofoctol MICs remain almost stable up to 96 h, after which the colonies are no longer detectable. The MICs of amoxicillin show a 2-fold increase starting from 36 h; however, at 120 h the colonies are no longer detectable. The MICs of erythromycin show a progressive increase starting from 72 h and reaching 32-fold. Clofoctol maintains its activity towards the common pathogens of respiratory tract infections and, similarly to amoxicillin, does not induce resistance in a strain of Streptococcus pneumoniae, resulting in complete eradication, while erythromycin was able to select resistant mutants., (© 2019 S. Karger AG, Basel.)

Background: Obesity has become a major public health challenge in recent years. Recent studies suggest that alterations of the gut microbiota by antibiotics could play an important role in obesity., Methods: We investigated this topic using 60 Wistar rats, which were divided into 3 experimental groups: rats treated with amoxicillin, rats treated with amoxicillin plus Saccharomyces boulardii and controls. Treatments were administered over the course of 2 weeks. Tetrapolar bioelectric impedance analysis and anthropometric evaluations were conducted., Results: The body mass index was significantly lower for the animals in the control group (p = 0.034). The same result was observed for the Lee index: the control group had a lower index than the 2 groups that received antibiotic treatment (p = 0.0019). The total body water data demonstrated that the control group had the greatest amount of body water (279.1 g, p = 0.0243)., Conclusions: The groups treated with the antibiotic exhibited a greater accumulation of body fat than the control group.

Background: It is suggested that antibiotherapy in infancy might program adult body composition and thus could be a determinant of obesity risk. Although not convincingly substantiated by existing literature, this assumption is plausible since antibiotics affect intestinal microbiota, whose composition in adulthood is potentially programmable during infancy and which is able to interact with both fat development and central control of appetite., Objectives: In order to substantiate the link between antibiotherapy and programming of adult body composition, the present study investigated the impact of a course of amoxicillin treatment in neonatal period on subsequent growth and body composition in rats., Methods: Suckling rat pups were treated by oral gavage with an amoxicillin solution (150 mg·kg(-1)) or vehicle from postnatal day (PND)5 to PND15. All animals were fully weaned at PND21 then fed a standard diet until PND130. Animal growth and food intake were followed up until PND130, when body composition and plasma leptin were measured. Faecal microbiota was typified at regular intervals using real-time quantitative polymerase chain reaction., Results: Preweaning amoxicillin treatment affected the composition of the faecal microbiota of pups at PND21 but this impact did not sustain long beyond the antibiotic supplementation. Immediately after weaning, a transient increase in food intake (+11%) was noticed in amoxicillin-treated animals. However, no significant impact on either growth or body composition at adulthood was observed., Conclusions: In a neonatal animal model there is no evidence of a programming of adult body weight and composition by wide-spectrum antibiotic treatment in early life., (Copyright © 2013 S. Karger AG, Basel.)

Background: Rabeprazole inhibits Helicobacter pylori in vitro. This property could influence the antibacterial activity of metronidazole or amoxicillin. Our goal was to evaluate in vitro the effect of rabeprazole upon the antibacterial activity of metronidazole and amoxicillin., Methods: The minimal inhibitory concentration (MIC) was determined by agar dilution upon 30 clinical isolates, and the antibacterial effect of the combined drugs was estimated by calculating the fractional inhibitory concentration index (FICI)., Results: Nine strains (30%) were resistant to metronidazole (MIC 8-256 mg/l) while only 1 strain was resistant to amoxicillin (MIC 1.0 mg/l). Rabeprazole also inhibited H. pylori (MIC 0.125-1.0 mg/l). The association of metronidazole and rabeprazole showed synergism in 30% of the strains (FICI < or =0.25), but also antagonism in 23.3% of the clinical isolates (FICI > or =4.0). Mostly, amoxicillin-rabeprazole showed an effect of synergism (53.3%)., Conclusion: The results presented suggest the need to keep in mind that failure in eradication therapies based on metronidazole and rabeprazole could be due to an antagonism of the drugs., (Copyright 2009 S. Karger AG, Basel.)

Background: Fluoroquinolone-resistant Helicobacter pylori emerged in 1995 and the resistance was due to point mutation in the gyrA gene. In this study we investigate the resistance mechanism and the antimicrobial susceptibilities of clarithromycin, metronidazole, amoxicillin, tetracycline and telithromycin against levofloxacin-resistant H. pylori in Hong Kong., Methods: One hundred and ninety-one nonduplicate H. pylori isolates were collected during 2004 and 2005, and 25 isolates with levofloxacin zone sizes less than 30 mm were selected for minimal inhibitory concentration determination by agar dilution, gyrA gene amplication and sequencing the amplified gyrA gene., Results: The prevalence of levofloxacin-resistant H. pylori was 11.5% (22/191). Among these levofloxacin-resistant strains, 7 (31.8%) and 10 (45.5%) were resistant to clarithromycin and metronidazole, respectively, 17 (77.3%) had point mutations in gyrA gene at amino acids 87, 91 and 130 and the most frequent mutation point was at position 91., Conclusions: Amoxicillin, tetracycline and telithromycin were active against levofloxacin-resistant H. pylori and levofloxacin resistance was mainly due to point mutation in the gyrA gene, especially at amino acid position 91., ((c) 2007 S. Karger AG, Basel.)

Background: Activity of simulated serum concentrations after oral therapy with 400 mg cefditoren pivoxil b.i.d., 500 mg cefuroxime axetil b.i.d. and 875/125 mg amoxicillin/clavulanic acid b.i.d. and t.i.d. regimens was explored over 24 h against Streptococcus pneumoniae., Methods: Computerized pharmacodynamic simulations were performed against strains with penicillin/amoxicillin/cefuroxime/cefditoren minimum inhibitory concentrations (MICs, microg/ml) and serotypes: strain 1 (0.25/0.12/1/0.12; serotype 6A), strain 2 (2/4/ 2/0.25; serotype 6B), strain 3 (4/16/4/0.5; serotype 14), and strain 4 (4/16/8/1; serotype 14)., Results: Bactericidal activity (> or =3 log(10) reduction) at 12 and 24 h was obtained against all strains with cefditoren, against strains 1 and 2 with cefuroxime and amoxicillin/clavulanic acid t.i.d., but only against strain 1 with amoxicillin/clavulanic acid b.i.d.. Bactericidal activity at 24 h was related to T > MIC of >30% dosing interval, 1.7-2.0 log(10) reductions with T > MIC of 20-30%, and <1 log(10) reduction or regrowth with T > MIC of 0%., Conclusions: It is difficult to achieve pharmacodynamic coverage and bactericidal activity by physiological concentrations of oral beta-lactams against penicillin-resistant pneumococcal strains exhibiting higher amoxicillin versus penicillin MICs. Cefditoren may offer alternatives.

Background: It is helpful in clinical practice to predict the effects of eradication therapy on Helicobacter pylori., Aim: To develop a useful predictor of the response to metronidazole (MNZ)-containing second-line regimens by combining minimal inhibitory concentrations (MICs) of both amoxicillin (AMX) and MNZ, and the results of urea breath test (UBT) before the treatment., Methods: We enrolled 107 patients who showed eradication failure following first-line triple therapy with a proton pump inhibitor, AMX and clarithromycin. The eradication resistance index was defined as: [pre-treatment UBT result ( per thousand)] x [AMX MIC (microg/ml)] x [MNZ MIC (microg/ml)]. Second-line eradication therapy with lansoprazole, AMX and MNZ was administered for 1 week. Eradication was confirmed by the UBT., Results: The eradication resistance index in subjects showing eradication failure and those showing successful eradication was 9.72 +/- 6.63 and 1.25 +/- 2.31, respectively (p < 0.001). When a cutoff value of 3 was used, the eradication resistance index predicted the response to therapy with a specificity of 93.8%, sensitivity of 81.8%, and accuracy of 92.5%., Conclusions: The eradication resistance index is a more useful predictor of response to MNZ-containing regimens for second-line treatment than only pretreatment UBT results or MNZ resistance.

Amoxicillin/sulbactam is a modern antimicrobial combination. This combination proved to be useful for the treatment of several infections caused by different microorganisms, mainly with the beta-lactamase-producing species. In this review we present the most relevant pharmacokinetic, pharmacodynamic and clinical information associated with its use.

Objective: To determine the resistance rate of the most commonly used antimicrobial agents amongst Helicobacter pylori isolates., Methods: The agar disk diffusion method (Kirby Bauer) was utilized to determine the susceptibility of 223 H. pylori strains isolated before treatment. Isolates were tested against metronidazole (5 micrograms), clarithromycin (15 micrograms), amoxycillin (10 micrograms), and tetracycline (30 micrograms)., Results: The resistance rate was 80% for metronidazole and 4% for clarithromycin. Tetracycline and amoxycillin showed very low degree of resistance with 1 (0.4%) and 3 (1.3%) of the strains resistant to these antibiotics, respectively. Age, sex and ethnicity had a remarkable effect on the resistance rate., Conclusion: The results indicate that metronidazole and clarithromycin should not be used as the only antimicrobial agents in the treatment of H. pylori infection. Susceptibility testing using the disk diffusion method is cost-effective in the screening of antimicrobial resistance against H. pylori.

Background: Amoxicillin and clarithromycin have been used extensively for the eradication of Helicobacter pylori. However, no study has examined the impact of their combination on the Candida albicans concentration of the gastrointestinal (GI) tract. This is the first study examining and comparing directly the effect of amoxicillin, clarithromycin and their combination on the C. albicans concentration of the human GI tract., Methods: Thirty-three adult patients (11 in each antibiotic group) were studied prospectively. Quantitative stool cultures for Candida were conducted at the beginning, the end and 1 week after the discontinuation of antibiotic treatment., Results: All three regimens increased the GI colonization in patients by Candida. The combination of amoxicillin with clarithromycin caused the highest increase; however, this was not statistically significant., Conclusion: Amoxicillin and clarithromycin used either alone or in combination cause a small to moderate increase in GI colonization by Candida. Hence, these drugs could be safely used in patients at risk for candidiasis originating from the GI tract., (Copyright 2001 S. Karger AG, Basel)

Background: An increased incidence of macrolide resistance in penicillin-resistant Streptococcus pneumoniae has been described., Methods: With this in mind, 216 S. pneumoniae isolates were evaluated for their in vitro susceptibility to a new fluoroquinolone, moxifloxacin, which was compared with penicillin, amoxicillin, cefuroxime, cefotaxime, ceftriaxone, erythromycin, clarithromycin, ciprofloxacin, sparfloxacin, ofloxacin, vancomycin and teicoplanin. A broth microdilution assay was performed in cation- adjusted Mueller-Hinton broth with 5% (v/v) lysed horse blood according to NCCLS guidelines., Results: Erythromycin resistance was observed in all the 22 penicillin-resistant S. pneumoniae (10.1%). All the penicillin- susceptible S. pneumoniae were susceptible to cephalosporins, whereas all the penicillin-resistant ones showed resistance to cefuroxime and only intermediate susceptibility to cefotaxime and ceftriaxone. The 216 tested strains were inhibited by sparfloxacin and moxifloxacin at concentrations of 0.12-0.5 mg/l and 0.06-0.25 mg/l, respectively, regardlesss of whether the strain was penicillin and/or erythromycin resistant. Seven penicillin-resistant strains displayed resistance to ofloxacin. All isolates were susceptible to vancomycin; teicoplanin MIC values ranged from 0.03 to 0.12 mg/l. The excellent in vitro activity of moxifloxacin against S. pneumoniae was not affected by penicillin and/or macrolides., Conclusion: Moxifloxacin appears to be a promising choice for the treatment of pneumococcal infections, including situations where therapeutic choices are limited due to penicillin and macrolide resistance., (Copyright 2001 S. Karger AG, Basel)

Clinical failure rates and the overuse of oral antibiotics are particularly acute in the case of non-complicated urinary tract infections (UTIs). Recent preliminary results from a major microbiological study in Spain have indicated significantly increased levels of resistance and insensitivity of isolated pathogens to commonly used antibiotics. Escherichia coli was by far the commonest pathogen isolated. Susceptibility was lowest with amoxicillin plus clavulanic acid, at 65.9% (334 of 507 gram-negative strains isolated). On the other hand, excellent susceptibility was noted with cefixime, corresponding to an MIC of <==4 microg/ml, at 99.2% (504 of 507). The results raise questions about the choice of antibiotics currently used in general practice, and suggest that cefixime may be a better first-line empiric treatment for noncomplicated UTIs.

The rising incidence of antibiotic resistance, including penicillin-resistant Streptococcus pneumoniae (PRSP), has become a great clinical problem in many countries. Cefixime, an orally active third-generation cephalosporin has broad and potent activity against various pathogens, especially gram-negative organisms including beta-lactamase producing strains. However, as with all other oral agents, cefixime is inactive against PRSP. As a possible solution to this problem, the effectiveness of a combination of cefixime and amoxicillin which retains stronger activity against PRSP was evaluated. This combination worked synergistically against S. pneumoniae including PRSP by the checkerboard method with a mean FIC index value of 0.60 and the time-kill kinetic method. Similarly, a synergistic effect was shown in the mouse respiratory tract infection model, with an FED index of 0.29 (cefixime:amoxicillin = 2:1). Additionally, this combination showed excellent activity against mixed organisms including PRSP, in the human serum level simulating kinetic method and mouse respiratory mixed infection models. We review here briefly preclinical studies carried out in our laboratory which demonstrate the synergistic effect of this cefixime plus amoxicillin combination, and suggest the empirical therapeutic potency of this combination for treating community-acquired respiratory tract infections, including PRSP, in the clinical setting.

Tazobactam and BRL 42715 are relatively new penems which inhibit a wide range of plasmid- as well as chromosomally mediated bacterial beta-lactamases that include Richmond and Sykes type I, II, III, IV and V beta-lactamases, staphylococcal penicillins and extended-spectrum beta-lactamases. However, clavulanic acid, which is a potent inhibitor of class III beta-lactamases, is one of the first discovered compounds. We used a total of 645 recent clinical isolates, consisting of 305 Enterobacteriaceae, 180 gram-positive cocci and 160 other gram-negative bacteria to evaluate the ability of beta-lactamase inhibitors for potentiation of piperacillin, ticarcillin and amoxycillin. Minimum inhibitory concentrations for all the 42 strains of methicillin-susceptible Staphylococcus aureus were reduced 4- to 16-fold in the presence of beta-lactamase inhibitors. They were also highly effective in inhibiting the beta-lactamase of a wide variety of gram-negative bacteria, thereby changing their MIC values for amoxycillin, ticarcillin and piperacillin from a 'resistant' to a 'susceptible' range. Commonly resistant bacteria like Klebsiella, Enterobacter, Serratia, Acinetobacter and Pseudomonas were rendered susceptible to piperacillin and ticarcillin in the presence of clavulanic acid, tazobactam and BRL 42715. Of the commercially available formulations for clinical use, piperacillin/tazobactam (Tazocin) was found to be more inhibitory towards both gram-positive and gram-negative bacteria.

A total of 266 enterobacterial isolates (Escherichia coli = 190, Klebsiella pneumoniae = 49, K. oxytoca = 27) were tested for susceptibility (Bauer-Kirby agar disk diffusion test and agar dilution procedure) to ampicillin, ampicillin in 10 micrograms/ml of sulbactam, amoxicillin in 4 micrograms/ml of clavulanic acid, piperacillin, piperacillin plus tazobactam (8:1 ratio), ticarcillin and timentin (ticarcillin in 4 micrograms/ml of clavulanic acid). Discrepant results between the two methods of susceptibility testing were categorized as follows: category I = very major [minimal inhibitory concentration (MIC) = resistant, disk diffusion = susceptible] category II = major (MIC = susceptible, disk diffusion = resistant), category III = minor (MIC = intermediate susceptibility, disk diffusion = susceptible), category IV = slight (MIC = resistant, disk diffusion = intermediate), category V = minimal (MIC = susceptible, disk diffusion = intermediate) and category VI = negligible (MIC = intermediate, disk diffusion = resistant). The antibiotics, or combinations with beta-lactamase inhibitors, yielded the following discrepant results: ampicillin (II = 2, V = 1 and VI = 3), co-amoxiclav (I = 5, III = 25, IV = 1 and V = 3), ampicillin plus sulbactam (I = 5, II = 3, III = 1, V = 19 and VI = 1), piperacillin (II = 15, III = 1, V = 15 and VI = 85), piperacillin plus tazobactam (III = 16, IV = 2, V = 1 and VI = 5) and timentin (I = 2, III = 48 and IV = 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Microbial adherence to epithelial cell surfaces has been implicated as the first step in the initiation of several infectious diseases. The ability of antibiotics to affect the properties of bacterial adherence to cell surfaces may be a criterion in selecting antibiotics for therapy. This study was performed in order to investigate the activity of amoxicillin, chloramphenicol, and clarithromycin in modifying the adhering activity of Bordetella pertussis to human epithelial cells. The actions of antibiotics, alone or combined with aprotinin, were compared with that of trypsin, aprotinin and trypsin+aprotinin, to investigate the chemical nature of the ligand where antibiotics could act. The adhering activity was evaluated on human epithelial cells, collected from the oral mucosa, challenged with B. pertussis A2963 previously incubated in the presence of the tested substances for 1 h at 37 degrees C in a shaker incubator. After staining, the percentage of mucosal cells with more than 50 adhering bacteria was evaluated. Under the described experimental conditions, trypsin significantly reduced the adherence of B. pertussis. Aprotinin had no effect but was able to counteract the inhibitory action of trypsin. Both clarithromycin and chloramphenicol markedly reduced adhering activity and their actions were not counteracted by aprotinin. Amoxicillin was without effect. It was hypothesized that chloramphenicol and clarithromycin, exerting their antimicrobial action by inhibiting bacterial protein synthesis, affected bacterial adhesion through an unknown mechanism without proteolytic effect.

Antimicrobial agents may interact with polymorphonuclear leukocytes and directly modify the leukocyte functions, or bacteria can be modified by the antimicrobial agents causing them to be treated differently by phagocytic cells. Brief exposure of bacteria to high levels of antimicrobials can affect their interaction with leukocytes. The susceptibility of Escherichia coli to phagocytosis and killing by human polymorphonuclear leukocytes in the presence of normal human serum following treatment with RP7293, a new natural streptogramin, was examined, and a comparison made with clavulanic acid/amoxicillin, ciprofloxacin and fosfomycin. Pretreatment of E. coli for 10 min with 4 x MIC of RP7293 clearly sensitized the bacteria to leukocytic killing in the presence of normal human serum (10% v/v).

An in vitro infection model was created using a suspension of macrophages, polymorphonuclear leukocytes, lymphocytes, fibroblasts, and human serum to which pathogen and antibiotic were added. Separate intracellular and extracellular antibiotic concentrations and activity against Staphylococcus aureus and Legionella pneumophila were assessed for three antimicrobial agents: amoxicillin, azithromycin and clarithromycin. Amoxicillin was found almost exclusively in extracellular fluid, where it was active; intracellularly, it was ineffective. Azithromycin, in contrast, was primarily concentrated and active intracellularly, with little activity in extracellular fluid. Clarithromycin was present in both compartments and possessed significant activity both intracellularly and extracellularly.

In a prospective randomised controlled trial, amoxycillin plus clavulanic acid was compared to a combination of cefotaxime and metronidazole as prophylactic antibiotics in 164 patients who underwent elective colorectal resectional surgery. Wound infection occurred in 15 patients (9.1%) and deep surgical infection in 4 (2.4%). Seven cases of wound infection and 2 cases of deep infection occurred in the amoxycillin plus clavulanic acid arm, while 8 cases of wound infection and 2 cases of deep infection occurred in the cefotaxime plus metronidazole arm. Eighty-eight percent of infections occurred in patients who had low anterior resection or abdominoperineal resection of the rectum. Both the amoxycillin plus clavulanic acid and the combination of cefotaxime and metronidazole offer the same degree of protection against post-operative infection. The use of amoxycillin plus clavulanic acid as antibiotic prophylaxis is recommended because of its easier use and cheaper cost.

BRL 42715 is a new penem which inhibits a wide range of plasmid as well as chromosomally mediated bacterial beta-lactamases. We used a total of 902 recent clinical isolates, consisting of 455 Enterobacteriaceae, 247 staphylococci and 200 other gram-negative bacteria to evaluate its ability for potentiation of amoxycillin. MICs for all the 104 strains of methicillin-susceptible Staphylococcus aureus were reduced from 8-greater than 32.0 to less than or equal to 0.06 micrograms/ml in the presence of 1-5 micrograms/ml of this penem. It was also highly effective in inhibiting the beta-lactamase of a wide variety of gram-negative bacteria, thereby bringing their MIC values for amoxycillin from a 'resistant' range (greater than 32.0 micrograms/ml) to a 'susceptible' range (less than or equal to 8.0 micrograms/ml). Commonly resistant bacteria like Klebsiella, Enterobacter, Citrobacter, Morganella, Serratia, Acinetobacter and Aeromonas were rendered susceptible to amoxycillin in the presence of 1.0-5.0 micrograms/ml of BRL 42715.

The minimum inhibitory concentration (MIC) of ofloxacin, ciprofloxacin, norfloxacin, amoxicillin and a new erythromycin analogue (azithromycin or CP 62993) against Chlamydia trachomatis was determined. There was a large difference between the MICs (microgram/ml) of different quinolones (median of 3 independent measurements; range): ofloxacin (0.5; 0.5-1) less than ciprofloxacin (1; 1-2) less than norfloxacin (16; 16-32). The MIC of amoxicillin varied from 0.25 to 1 (median 0.5) in different experiments. The MIC of azithromycin (0.125; 0.063-0.25) was lower than that of erythromycin (0.25; 0.125-0.5). The minimum lethal concentration (MLC) of ofloxacin and azithromycin was determined with and without passage of the McCoy cells. Both methods gave the same results. Ofloxacin seemed to have a lethal effect on C. trachomatis, as the MIC and MLC were equal. In contrast, the effect of the MIC of azithromycin on C. trachomatis was bacteriostatic. The MLC of azithromycin was 2-4 times higher than the MIC (p less than 0.001).

The antimicrobial activities of nalidixic acid-cephalexin (ratio 1:1) and cinoxacin-cefadroxil (ratio 1:2) combinations have been evaluated against 396 clinical isolates; many of them were nalidixic acid- or cinoxacin-resistant organisms (MIC greater than or equal to 100 micrograms/ml). We have also tested the nalidixic acid-amoxicillin combination (ratio 1:1) against 225 amoxicillin-resistant bacterial strains (MIC greater than or equal to 800 micrograms/ml). Synergy was found for 62-70% of the Enterobacteriaceae and nonfermenter bacilli tested and for 85-92% of the gram-positive bacterial strains. The 225 clinical isolates resistant to amoxicillin (MIC greater than or equal to 800 micrograms/ml) were synergistically inhibited by the nalidixic acid-amoxicillin combination.

The in vitro study of the amoxicillin-clavulanate association has been carried out using a triple layer technique by means of paper strips which show a T configuration. Synergy observation proves to be most favorable with the following reservoir load: (a) when the latter is sufficiently low so that the inhibiting effect of the clavulanate and amoxicillin, taken in isolation, becomes weak or nil; (b) when the ratio between the two substances is amoxicillin 5, clavulanate 1. Under such conditions, the inhibition of the bacterial growth occurs solely in the confluence area of the substances. The neutralization of amoxicillin through penicillinase respectively after 4, 6 and 24 h of incubation makes possible an appraisal of the bactericidal action of the association.

The rate of bactericidal activity of a new macrolide, CP-62,993, was compared with that of the combination of amoxicillin and clavulanic acid (in the proportion of 4 to 1) on strains of Branhamella catarrhalis beta-lactamase producers. The antibacterial activity of CP-62,993 was bacterostatic at 0.01 micrograms/ml. After a 6-hour period of bacteriostasis a bactericidal activity (3 log10 CFU/ml) was observed for all concentrations from 0.1 to 10 micrograms/ml after 24 h. The bactericidal rate of amoxicillin-clavulanic acid combination was more rapid during the first 6 h at 1 and 10 micrograms/ml. However, the concentration required to kill 99.9% of bacteria within 24 h was 1 microgram/ml. In conclusion, CP-62,993 was a bactericidal antibiotic for B. catarrhalis at a lower concentration. This in vitro study suggests that this macrolide may be of great interest in infections due to the B. catarrhalis beta-lactamase producer.

The antibacterial activities of three aminopenicillins ampicillin, epicillin and amoxycillin were compared in vitro and in vivo. The minimum inhibitory concentrations (MIC) of the three penicillins were very similar and the compounds were active against non-beta-lactamase-producing strains of Escherichia coli, Salmonella and Shigella species, Proteus mirabilis, Haemophilus influenzae and Neisseria gonorrhoeae. Streptococci including Streptococcus faecalis, and non-beta-lactamase-producing staphylococci were also sensitive to the compounds but Pseudomonas aeruginosa, Klebsiella aerogenes, Enterobacter and indole-positive Proteus species were resistant. At concentrations close to MIC value epicillin and ampicillin showed similar bactericidal activity against E. coli and against S. typhi and both compounds caused a slower rate of kill than was seen with amoxycillin. Microscopical observation of the cells exposed to ampicillin and epicillin for 1 h showed the presence of filamentous forms which lysed slowly, whereas cells exposed to amoxycillin for the same period rapidly. Epicillin was similar to or slightly less active than ampicillin against experimental mouse infections, and against the majority of infections both compounds were significantly less effective than amoxycillin by the oral and subcutaneous routes of administration.

17,244 pathogens isolated from clinical specimens of 24 hospitals in the Moers area (North-Rhine Westphalia, FRG) were tested in regard to their susceptibility to Augmentin (amoxicillin and clavulanic acid). For this purpose, minimal inhibitory concentrations were determined by use of microbroth dilution technique. 80% of Gram-negative, 98% of Gram-positive and 97% of anaerobic isolates were susceptible to Augmentin (breakpoint 4 mg/l amoxicillin in the presence of 2.5 mg/l clavulanic acid). In a second part of the study the susceptibility to Augmentin of 4.137 Gram-negative and 10.958 Gram-positive pathogens was compared to their sensitivity against benzylpenicillin, flucloxacillin, mezlocillin, erythromycin, clindamycin, fusidic acid, ampicillin, cefaclor and doxycyclin.

The antibacterial activity of a combination of equal parts of amoxycillin and flucloxacillin was compared in vitro and in vivo with that of amoxycillin and flucloxacillin against a range of gram-positive and gram-negative bacteria. The combination generally showed additive effects against bacteria sensitive to the individual penicillins and there was no evidence of antagonism, but synergistic effects were observed between amoxycillin and flucloxacillin against certain amoxycillin-resistant gram-negative bacilli. The extent of synergism varied according to the particular bacterial species under test and synergy was observed only against bacteria with chromosomally-mediated beta-lactamases and not against bacteria with R-factor-mediated beta-lactamases. In general, amoxycillin + flucloxacillin demonstrated activity against experimental mouse infections in good agreement with demonstrated activity against experimental mouse infections in good agreement with its in vitro activity, and synergy was produced against a range of gram-negative bacilli in vivo. The data suggest that clinical trial with amoxycillin + flucloxacillin in the treatment of selected infections including those due to some amoxycillin-resistant bacteria may well be justified.

Streptococcus faecalis usually requires high concentrations of penicillin or ampicillin to achieve killing (i.e. a high MBC/MIC ratio). However, most strains show the Eagle or paradoxical effect. We subjected 12 strains of S. faecalis to 0.1, 1, 10 and 100 micrograms/ml of amoxicillin. Turbidometry studies have shown that 3 h after the inactivation of amoxicillin by penicillinase, there was a longer effect for 1 micrograms/ml following beta-lactamase (12 h 31 min +/- 2 h 09 min) than for 10 micrograms/ml (7 h 0 min +/- 1 h 12 min) or 100 micrograms/ml (5 h 22 min +/- 0 h 52 min). After 3 h, the reduction of CFU/ml (inoculum 10(6) CFU/ml) was -1.8 +/- 0.6 for 1 micrograms/ml, -0.56 +/- 0.56 for 10 micrograms/ml and -0.21 +/- 0.20 for 100 micrograms/ml. The more rapid killing at 3 h was not the only reason for the longer effect following beta-lactamase observed with 1 micrograms/ml. Indeed, the growth curve obtained with an inoculum of 10(3) CFU/ml was 2 h delayed from the control curve (10(6) CFU/ml). In conclusion, a paradoxical effect (killing curves and effect following beta-lactamase) was observed for all S. faecalis strains included in this series.

190 isolates from clinical specimens were tested in vitro to determine their susceptibility pattern against augmentin. Of the 132 strains of Enterobacteriaceae tested, 109 (82.6%) were susceptible. 41 (93.2%) of the 44 gram-positive bacteria tested were also susceptible to augmentin. Strains of Pseudomonas aeruginosa and Serratia marcescens were resistant to augmentin. However, augmentin showed increased activity against Escherichia coli, and Staphylococcus aureus when compared with ampicillin.

30 representative intrinsically penicillin-resistant coagulase-negative staphylococcal (CONS) isolates yielded discrepant agar disk diffusion test (Bauer-Kirby) results for augmentin. Clavulanic acid (2.5 micrograms/ml) enhanced the activity of amoxycillin from 8- to greater than or equal to 128-fold (mean = 26-fold); MICs of amoxycillin (combined with 2.5 micrograms/ml clavulanate) ranged from 1-16 (mean = 3) micrograms/ml. It is recommended that clinical microbiology laboratories withhold 'susceptible' augmentin disk tests results from their reports regarding intrinsically penicillin-resistant CONS isolates. No such discrepancies were encountered among clinical isolates of Staphylococcus aureus.

Cefotaxime has extremely low MIC values in comparison with amoxycillin against Enterobacteriaceae, but studies of antibacterial activity using turbidimetric and viable count methods show no advantage for cefotaxime. Superior rates of killing have been demonstrated for amoxycillin and amoxycillin/clavulanic acid using both constant antibiotic concentrations and changing concentrations to simulate conditions in vivo. Slow bactericidal activity was seen with cefotaxime even at levels greatly in excess of the MIC and could be correlated with filament formation by this compound over a wide range of concentrations.