amoxicillin-potassium-clavulanate-combination and Pneumonia--Pneumococcal

Pharmacokinetic (PK) and pharmacodynamic (PD) principles that predict antimicrobial efficacy can be used to set targets for antimicrobial design and optimisation. Although current formulations of amoxicillin and amoxicillin/clavulanate have retained their efficacy against many, but not all, penicillin-nonsusceptible Streptococcus pneumoniae, additional coverage is required to address the growing problem of drug-resistant strains. Accordingly, two new oral formulations of amoxicillin/clavulanate, a paediatric formulation at 90/6.4 mg/kg/day and a pharmacokinetically enhanced formulation at 2000/125 mg twice daily for adults, were designed using PK/PD principles. These principles indicate that for amoxicillin and amoxicillin/clavulanate, a time above MIC of 35-40% of the dosing interval is predictive of high bacterial efficacy. In line with PK/PD predictions, simulation of human pharmacokinetics in in-vitro kinetic models and in a rat model of pneumonia, amoxicillin/clavulanate 2000/125 mg twice daily was highly effective against S. pneumoniae strains with amoxicillin MICs of 4 or 8 mg/L. Against strains with amoxicillin MICs of 4 mg/L, amoxicillin/clavulanate 2000/125 mg twice daily was significantly more effective than the conventional 875/125 mg twice daily formulation, azithromycin and levofloxacin, even though all levofloxacin MICs were < or = 1 mg/L. Following infection with S. pneumoniae strains with amoxicillin MICs of 8 mg/L, the amoxicillin/clavulanate 2000/125 mg twice daily formulation was more effective than the conventional amoxicillin/clavulanate formulations of 875/125 mg twice daily and three times daily and 1000/125 mg three times daily, and had similar or better efficacy than azithromycin and levofloxacin, depending on the strain. These data indicate the potential benefit of therapy with amoxicillin/clavulanate 2000/125 mg twice daily compared with conventional formulations and other marketed antimicrobials in the treatment of respiratory tract infection.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Disease Models, Animal; Drug Design; Humans; Microbial Sensitivity Tests; Models, Biological; Pneumonia, Pneumococcal; Rats; Streptococcus pneumoniae; Time Factors; Treatment Outcome

The development of our understanding of the pharmacokinetic (PK) and pharmacodynamic (PD) principles that determine antimicrobial efficacy has advanced substantially over the last 10 years. We are now in a position to use PK/PD principles to set targets for antimicrobial design and optimisation so that we can predict eradication of specific pathogens or resistant variants when agents are used clinically. Optimisation of PK/PD parameters to enable the treatment of resistant pathogens with oral agents may not be possible with many current agents, such as some cephalosporins, macrolides and fluoroquinolones. Aminopenicillins, however, such as amoxicillin, have linear PK and have a good safety profile even at high doses. The new pharmacokinetically enhanced oral formulation of amoxicillin/clavulanate, 2000/125 mg twice daily, was designed using PK/PD principles to be able to eradicate Streptococcus pneumoniae with amoxicillin MICs of up to and including 4 mg/L, which includes most penicillin-resistant isolates. For amoxicillin and amoxicillin/clavulanate, a time above MIC (T > MIC) of 35-40% of the dosing interval (based on blood levels) is predictive of high bacteriological efficacy. This target was met by the design of a unique bilayer tablet incorporating 437.5 mg of sustained-release sodium amoxicillin in one layer plus 562.5 mg of immediate-release amoxicillin trihydrate and 62.5 mg of clavulanate potassium in the second layer, with two tablets administered for each dose. This unique design extends the bacterial killing time by increasing the T > MIC to 49% of the dosing interval against pathogens with MICs of 4 mg/L, and 60% of the dosing interval against pathogens with MICs of 2 mg/L. Based on these results, this new amoxicillin/clavulanate formulation should be highly effective in treating respiratory tract infections due to drug-resistant S. pneumoniae as well as beta-lactamase-producing pathogens, such as Haemophilus influenzae and Moraxella catarrhalis.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Drug Design; Drug Resistance, Bacterial; Humans; Mice; Microbial Sensitivity Tests; Pneumonia, Pneumococcal; Streptococcus pneumoniae; Time Factors; Treatment Outcome

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bronchitis; Double-Blind Method; Drug Therapy, Combination; Haemophilus Infections; Haemophilus influenzae; Humans; Moraxella catarrhalis; Multicenter Studies as Topic; Neisseriaceae Infections; Pneumonia; Pneumonia, Pneumococcal; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus aureus; Streptococcus pneumoniae

A regimen of cefprozil (500 mg twice daily), a new oral cephalosporin with a broad in vitro spectrum of antimicrobial activity, was compared to standard regimens of cefaclor (500 mg three times daily), cefuroxime axetil (500 mg twice daily), or amoxicillin/clavulanate (500 mg/125 mg three times daily) for the treatment of lower respiratory tract infections (mainly bronchitis and acute exacerbations of chronic bronchitis) in adults in three open-label, randomized trials. In the first trial, in which bacterial pathogens were isolated in initial cultures for only one-third of the patients, 90% of the pathogens were susceptible to cefprozil. A satisfactory clinical response was noted for 84% of the evaluable patients who received cefprozil versus 79% of those who received cefaclor for treatment of lower respiratory tract infections; rates of bacteriologic efficacy were 82% and 78%, respectively. In the second study rates of satisfactory clinical response were 96% with cefprozil and 83% with cefuroxime axetil (P less than .03) for treatment of bronchitis; the respective bacteriologic response rates were 100% and 92%. In the third trial, clinical efficacy was 91% for cefprozil and 87% for amoxicillin/clavulanate for treatment of bronchitis; bacteriologic efficacy was 95% and 96%, respectively. Tolerability and safety profiles were comparable, except that there was a higher rate of diarrhea among patients who received amoxicillin/clavulanate (P = .03).

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Bronchitis; Bronchopneumonia; Cefaclor; Cefprozil; Cefuroxime; Cephalosporins; Clavulanic Acids; Drug Therapy, Combination; Humans; Pneumonia, Pneumococcal

This randomized, double-blind, non-inferiority trial evaluated the efficacy and safety of pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg twice daily versus amoxicillin/clavulanate 875/125 mg three times daily, both given orally for 7 or 10 days, in the treatment of adults with community-acquired pneumonia in Spain, a country with a high prevalence of penicillin-resistant Streptococcus pneumoniae.. Following 2:1 randomization, 566 patients (intent-to-treat population) received either amoxicillin/clavulanate 2000/125 mg (n = 374) or amoxicillin/clavulanate 875/125 mg (n = 192).. Among the patients who did not deviate from the protocol (clinical per-protocol population), clinical success at day 21-28 post-therapy (test of cure; primary efficacy endpoint) was 92.4% (266/288) for amoxicillin/clavulanate 2000/125 mg and 91.2% (135/148) for amoxicillin/clavulanate 875/125 mg (treatment difference, 1.1; 95% confidence interval, -4.4, 6.6). Bacteriological success at test of cure in the bacteriology per-protocol population was 90.8% (79/87) with amoxicillin/clavulanate 2000/125 mg and 86.0% (43/50) with amoxicillin/clavulanate 875/125 mg (treatment difference 4.8; 95% confidence interval, -6.6, 16.2). At test of cure, amoxicillin/clavulanate 2000/125 mg was clinically and bacteriologically effective against 7/7 penicillin-resistant Streptococcus pneumoniae (MIC > or = 2 mg/L) isolates (including three amoxicillin non-susceptible strains) and amoxicillin/clavulanate 875/125 mg against 5/5 isolates (including one amoxicillin non-susceptible strain).. Both treatment regimens were well tolerated. Amoxicillin/clavulanate 2000/125 mg was at least as effective clinically and as safe as amoxicillin/clavulanate 875/125 mg in the treatment of community-acquired pneumonia in adults in a country with a high prevalence of penicillin-resistant S. pneumoniae and has a more convenient twice daily posology.

Topics: Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Community-Acquired Infections; Double-Blind Method; Female; Humans; Male; Middle Aged; Penicillin Resistance; Pneumonia, Pneumococcal; Spain; Streptococcus pneumoniae

To compare the efficacy of sequential injectable crystalline penicillin (C.pen) and gentamicin combination followed by oral amoxicillin with sequential IV and oral amoxicillin-clavulanate (amox-clav) in treatment of severe or very severe hypoxemic pneumonia.. Children aged 2-59 months with WHO-defined severe or very severe pneumonia with hypoxemia (SpO2 < 90%) were included in the study. Patients with fever > 10 days, bacterial meningitis, prior antibiotic therapy > 24 hours, stridor, heart disease and allergy to any of the study drugs were excluded. They were randomly allocated to two groups--Group A and Group B. Group A received C. pen and gentamicin intravenously (IV), followed by oral amoxicillin and group B got amox-clav IV, followed by oral amox-clav. Minimum duration of IV therapy was 3 days and total 7 days. Respiratory rate, oxygen saturation and chest wall indrawing were monitored 6 hourly.. 71 patients were included. There were two (5.2%) blood cultures positive in group A and three (9%) in group B. Organisms isolated were S. pneumoniae (n=3) and H. influenzae-b (n=2). There was only one treatment failure in each of the groups. One was due to penicillin resistant H. influenzae -b and the other was due to worsening of pneumonia. The mean time taken for normalization of tachypnea, hypoxia, chest wall indrawing and inability to feed was similar (P-N.S). Mean duration of IV therapy in group A was 76+/-25 hrs and group B was 75+/-24 hrs (p>0.1).. In children of 2-59 months, sequential injectable C. pen and gentamicin combination, followed by oral amoxicillin or sequential IV and oral amox-clav were equally effective for the treatment of severe or very severe hypoxemic community acquired pneumonia.

Topics: Administration, Oral; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child, Preschool; Drug Therapy, Combination; Female; Gentamicins; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Infusions, Intravenous; Male; Penicillins; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Treatment Outcome

Community-acquired pneumonia (CAP) is a common respiratory illness, frequently caused by Streptococcus pneumoniae. The prevalence of S. pneumoniae resistance to common antimicrobials has increased over recent years. A new pharmacokinetically enhanced formulation of amoxicillin/clavulanate (2000/125 mg) has been developed, designed to combat infections caused by S. pneumoniae, including penicillin-resistant (PRSP, penicillin minimum inhibitory concentrations (MICs) >or=2mg/l) isolates, and those with elevated amoxicillin/clavulanic acid MICs, while maintaining coverage of beta-lactamase-producing pathogens. A pooled efficacy analysis of four randomized (1:1) and one non-comparative clinical trials of amoxicillin/clavulanate, 2000/125 mg, given twice daily, was conducted in adult patients with CAP. Comparator agents were conventional amoxicillin/clavulanate formulations. At follow-up (days 16-39), efficacy (eradication of the initial pathogen or clinical cure in patients for whom no repeat culture was performed) in patients with S. pneumoniae infection was 92.3% (274/297) for amoxicillin/clavulanate, 2000/125 mg and 85.2% (46/54) for comparators (P=0.11). Twenty-four of 25 PRSP-infected patients receiving amoxicillin/clavulanate, 2000/125 mg were treated successfully. Both amoxicillin/clavulanate, 2000/125 mg and comparators were well tolerated, with few patients withdrawing from the studies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Community-Acquired Infections; Double-Blind Method; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Penicillin Resistance; Pneumonia, Pneumococcal; Streptococcus pneumoniae; Treatment Outcome

Pharmacokinetically enhanced co-amoxiclav 2000/125 mg was designed to achieve high serum concentrations of amoxicillin over the 12 h dosing interval to eradicate Streptococcus pneumoniae with amoxicillin MICs of at least 4 mg/L.. This randomized, double-blind, double-dummy, multicentre study compared the efficacy and safety of oral co-amoxiclav 2000/125 mg twice daily versus co-amoxiclav 875/125 mg three times daily, for 7 or 10 days, in the treatment of community-acquired pneumonia (CAP).. The per-protocol (PP) population at follow-up (Days 18-39) comprised 114 patients receiving co-amoxiclav 2000/125 mg and 116 receiving co-amoxiclav 875/125 mg. Clinical success at follow-up (primary efficacy endpoint) in the clinical PP population was 94.7% (108/114) for co-amoxiclav 2000/125 mg versus 88.8% (103/116) for co-amoxiclav 875/125 mg [treatment difference (TD) = 5.9%, 95% CI: 1.1, 13.0]. Bacteriological success in the bacteriology PP population at follow-up was 85.0% (17/20) for co-amoxiclav 2000/125 mg versus 77.3% (17/22) for co-amoxiclav 875/125 mg (TD = 7.7%, 95% CI: 15.8, 31.2). Penicillin-resistant S. pneumoniae (PRSP) were isolated in three patients (including two with bacteraemia) in the co-amoxiclav 2000/125 mg group (amoxicillin MICs 8 mg/L, penicillin MICs 4 mg/L) and one in the comparator group; all were clinical and bacteriological successes. Co-amoxiclav 2000/125 mg and co-amoxiclav 875/125 mg were associated with adverse events leading to withdrawal in 6.3% and 6.2% of patients, respectively.. Co-amoxiclav 2000/125 mg twice daily was at least as effective clinically as co-amoxiclav 875/125 mg three times daily in the treatment of CAP. Although few patients in this study had PRSP infection, 3/3 were successfully treated with co-amoxiclav 2000/125 mg.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Community-Acquired Infections; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pneumonia, Pneumococcal; Streptococcus pneumoniae; Treatment Outcome

This double-blind, double-dummy, parallel-group study was designed to show that a pharmacokinetically enhanced formulation of oral amoxycillin-clavulanate (16:1, 2000/125 mg), twice daily, is at least as effective clinically and microbiologically as oral amoxycillin-clavulanate 1000/125 mg, three times daily, in the 10 day treatment of community-acquired pneumonia (CAP) in adults. The pharmacokinetically enhanced formulation is designed to provide higher serum concentrations of amoxycillin for a longer period than standard dosing to achieve coverage of Streptococcus pneumoniae isolates with amoxycillin-clavulanic acid minimum inhibitory concentrations (MICs) up to and including 4 mg/l. A total of 344 patients with CAP from 77 centres received amoxycillin-clavulanate 2000/125 mg twice daily for 10 days (169 patients) or amoxycillin-clavulanate 1000/125 mg three times daily for 10 days (175 patients). The most common pathogen isolated was S. pneumoniae (52.3% of patients, amoxycillin-clavulanate 2000/125 mg group; 46.8% of patients, amoxycillin-clavulanate 1000/125 mg group). In the clinical per-protocol (PP) population at test of cure (days 18-39), the clinical success rate in the amoxycillin-clavulanate 2000/125 mg group was at least as good as in the amoxycillin-clavulanate 1000/125 mg group (91.5 and 93.0%, respectively; 95% CI, -8.3, 5.4). The radiological and bacteriological success rates at test of cure for the PP populations were 92.4 and 90.6% in the amoxycillin-clavulanate 2000/125 mg group and 93.9 and 84.4% in the amoxycillin-clavulanate 1000/125 mg group, respectively. The clinical, bacteriological and radiological success rates at the end of therapy (days 11-17) for the PP populations were all over 85%. Both regimens were well tolerated, with no differences in adverse events between the groups. Amoxycillin-clavulanate 2000/125 mg, twice daily, is well tolerated and at least as effective clinically as amoxycillin-clavulanate 1000/125 mg, three times daily, in patients with CAP and may also be appropriate for the treatment of infections due to S. pneumoniae strains with high-level penicillin resistance.

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Community-Acquired Infections; Double-Blind Method; Drug Therapy, Combination; Female; Haemophilus influenzae; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Penicillin Resistance; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Streptococcus pneumoniae; Treatment Outcome

Cefditoren pivoxil is a broad-spectrum cephalosporin that is approved for the treatment of pharyngitis, acute exacerbations of chronic bronchitis, and skin and skin-structure infections.. This study was conducted to examine the efficacy and tolerability of cefditoren in the treatment of community-acquired pneumonia (CAP). Amoxicillin/clavulanate was chosen as a comparator because of its established efficacy and general acceptance as a standard of care in CAP.. This multicenter, prospective, randomized, investigator-blinded, parallel-group trial compared oral cefditoren 200 and 400 mg BID with oral amoxicillin/clavulanate 875/125 mg BID for 14 days in adult outpatients with CAP.. Eight hundred two patients (404 men, 398 women; mean age, 50 years; age range, 12-93 years) with CAP were enrolled. Comparable clinical cure rates were observed among evaluable patients in all treatment groups at both the posttreatment and follow-up visits: 88.0% (125/142) for cefditoren 200 mg, 89.9% (143/159) for cefditoren 400 mg, and 90.3% (130/144) for amoxicillin/clavulanate at the posttreatment visit, and 86.5% (128/148), 86.8% (138/159), and 87.8% (129/147) for the respective groups at the follow-up visit. Of 82 Streptococcus pneumoniae strains isolated before treatment, 22 (26.8%) had reduced susceptibility to penicillin, 12 (14.6%) of them penicillin resistant. Overall eradication rates at the posttreatment visit for pathogens isolated from microbiologically evaluable patients were 84.0%, 88.6%, and 82.6% for cefditoren 200 mg, cefditoren 400 mg, and amoxicillin/clavulanate, respectively. In the respective treatment groups, 80.6%, 88.6%, and 88.0% of Haemophilus influenzae strains and 95.0%, 96.2%, and 89.5% of S pneumoniae strains were eradicated. The rates of resolution of or improvement in clinical signs and symptoms were comparable between treatment groups. The treatment regimens were well tolerated, with 4.9%, 3.0%, and 5.2% of patients in the respective treatment groups requiring discontinuation of study drug due to an adverse event.. In this study in adult outpatients with CAP, both doses of cefditoren demonstrated equivalence to amoxicillin/clavulanate based on rates of clinical and microbiologic cure. All 3 regimens were effective in resolving or improving the clinical signs and symptoms of CAP. Both cefditoren and amoxicillin/ clavulanate were well tolerated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cephalosporins; Child; Community-Acquired Infections; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Pneumococcal; Prospective Studies; Researcher-Subject Relations; Streptococcus pneumoniae; Treatment Outcome; United States

A regimen of cefprozil (500 mg twice daily), a new oral cephalosporin with a broad in vitro spectrum of antimicrobial activity, was compared to standard regimens of cefaclor (500 mg three times daily), cefuroxime axetil (500 mg twice daily), or amoxicillin/clavulanate (500 mg/125 mg three times daily) for the treatment of lower respiratory tract infections (mainly bronchitis and acute exacerbations of chronic bronchitis) in adults in three open-label, randomized trials. In the first trial, in which bacterial pathogens were isolated in initial cultures for only one-third of the patients, 90% of the pathogens were susceptible to cefprozil. A satisfactory clinical response was noted for 84% of the evaluable patients who received cefprozil versus 79% of those who received cefaclor for treatment of lower respiratory tract infections; rates of bacteriologic efficacy were 82% and 78%, respectively. In the second study rates of satisfactory clinical response were 96% with cefprozil and 83% with cefuroxime axetil (P less than .03) for treatment of bronchitis; the respective bacteriologic response rates were 100% and 92%. In the third trial, clinical efficacy was 91% for cefprozil and 87% for amoxicillin/clavulanate for treatment of bronchitis; bacteriologic efficacy was 95% and 96%, respectively. Tolerability and safety profiles were comparable, except that there was a higher rate of diarrhea among patients who received amoxicillin/clavulanate (P = .03).

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Bronchitis; Bronchopneumonia; Cefaclor; Cefprozil; Cefuroxime; Cephalosporins; Clavulanic Acids; Drug Therapy, Combination; Humans; Pneumonia, Pneumococcal

Although antibiotic de-escalation is regarded as a measure that reduces selection pressure, adverse drug effects and costs, evidence supporting this practice in community-acquired pneumococcal pneumonia (CAPP) is lacking.. We carried out a retrospective analysis of prospectively collected data of a cohort of hospitalized adults with CAPP. Pneumococcal aetiology was established in patients with one or more positive cultures for Streptococcus pneumoniae obtained from blood, sterile fluids or sputum, and/or a positive urinary antigen test. De-escalation therapy was considered when the initial antibiotic therapy was narrowed to penicillin, amoxicillin or amoxicillin/clavulanate within the first 72 h after admission. The primary outcomes were 30 day mortality and length of hospital stay (LOS). Adjustment for confounders was performed with multivariate and propensity score analyses.. Of 1410 episodes of CAPP, antibiotic de-escalation within the first 72 h after admission was performed in 166 cases. After adjustment, antibiotic de-escalation was not associated with a higher risk of mortality (OR = 0.83, 95% CI = 0.24-2.81), but it was found to be a protective factor for prolonged LOS (above the median) (OR = 0.46, 95% CI = 0.30-0.70). Similar results were found in patients classified into high-risk pneumonia severity index classes (IV-V), those with clinical instability and those with bacteraemia. No significant differences were documented in adverse drug reactions or readmission (<30 days).. Antibiotic de-escalation seems to be safe and effective in reducing the duration of LOS, and did not adversely affect outcomes of patients with CAPP, even those with bacteraemia and severe disease, and those who were clinically unstable.

Topics: Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteremia; Community-Acquired Infections; Female; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Penicillins; Pneumonia, Pneumococcal; Prospective Studies; Retrospective Studies; Streptococcus pneumoniae; Treatment Outcome

To determine the susceptibility of lower respiratory tract (LRT) isolates of Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae to antimicrobial agents recommended by UK guidelines for treatment of pneumonia associated with influenza-like illness.. Analysis of antimicrobial susceptibility data from sentinel microbiology laboratories in England, Wales and Northern Ireland was carried out. Subjects comprised patients who had an LRT specimen taken in a general practitioner surgery or hospital outpatient setting between January 2007 and March 2010. The main outcome measurements were antimicrobial susceptibility trends of LRT isolates over time, between patient age groups and in different geographical regions.. Susceptibility to tetracyclines or co-amoxiclav was high. Of the 70,288 and 45,288 isolates with susceptibility results for tetracyclines or co-amoxiclav, 96% and 92%, respectively, were susceptible. Overall susceptibility to ciprofloxacin, ampicillin/amoxicillin and macrolides was lower than for tetracyclines or co-amoxiclav and varied markedly by organism. There were few clinically relevant variations in susceptibility to doxycycline or co-amoxiclav over time, geographically or between age groups.. The data support the use of doxycycline or co-amoxiclav as appropriate empiric treatment for LRT infection caused by the pathogens investigated, for patients in primary care.

Topics: Adult; Age Factors; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Databases, Factual; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Influenza, Human; Male; Microbial Sensitivity Tests; Middle Aged; Opportunistic Infections; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Primary Health Care; Staphylococcal Infections; Staphylococcus aureus; Streptococcus pneumoniae; Tetracyclines

Topics: Amoxicillin-Potassium Clavulanate Combination; Antibiotic Prophylaxis; Bronchi; Cefamandole; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Microbial Sensitivity Tests; Pneumonectomy; Pneumonia, Pneumococcal; Postoperative Complications; Pulmonary Disease, Chronic Obstructive; Risk; Treatment Outcome

Topics: Adult; Aged; Ambulatory Care; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Ceftriaxone; Female; Humans; Male; Middle Aged; Patient Admission; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Pneumonia, Viral; Risk Factors; Systemic Inflammatory Response Syndrome

Few attempts have been made to compare bacteremic and non-bacteremic pneumococcal pneumonia, mainly because it is difficult to gain agreement on which cases represent non-bacteremic pneumococcal pneumonia. Recently, an immunochromatographic assay for the detection of Streptococcus pneumoniae urinary antigen has been successfully evaluated for the diagnosis of pneumococcal pneumonia. The aim of our study was to examine and compare clinical and radiological features, risk factors, and outcome associated with bacteremic and non-bacteremic groups.. A retrospective study (1995-2003) analyzing the clinical records of patients diagnosed with pneumococcal pneumonia in our institution was performed. S. pneumoniae were identified by blood cultures (bacteremic group) and detection of urinary antigen (non-bacteremic group).. There were 82 patients (57 bacteremic and 25 non-bacteremic). In seven non-bacteremic cases, another etiology was detected, i.e., Legionella (n=1) and Chlamydia pneumoniae (n=6). Bacteremic patients were significantly younger (p=<0.001), more likely to have liver disease (p=0.028), current smokers (p=0.024), alcohol and intravenous drug abusers (p=0.014 and p<0.001, respectively), and infected with HIV (p<0.001). Non-bacteremic patients were more likely to have congestive heart failure (p=0.004), chronic obstructive pulmonary disease (p=0.033) and to be former smokers (p=0.004). Bacteremic cases needed more prolonged intravenous antibiotic treatment (6 days vs. 4.5 days; p=0.006) than non-bacteremic cases and their length of stay was also longer.. In our study, smoking was the leading risk factor for pneumococcal pneumonia. However, current smokers have an increased risk of bacteremic forms and former smokers and patients with COPD developed non-bacteremic forms more frequently. Bacteremic patients need more prolonged intravenous antibiotic treatment than non-bacteremic patients.

Topics: Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Antigens, Bacterial; Bacteremia; Cephalosporins; Community-Acquired Infections; Female; Fluoroquinolones; Humans; Length of Stay; Macrolides; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Pneumococcal; Retrospective Studies; Streptococcus pneumoniae; Treatment Outcome

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Clindamycin; Community-Acquired Infections; Doxycycline; Drug Therapy, Combination; Humans; Pneumonia, Pneumococcal; Streptococcus pneumoniae

Two models of respiratory tract infection were used to investigate the pharmacodynamics of amoxicillin-clavulanate against Streptococcus pneumoniae. Eight strains of S. pneumoniae were used in a mouse model in which the animals were infected intranasally and were then treated with a range of doses and dose intervals. The time that the plasma amoxicillin concentration remained above the MIC (T>MIC) correlated well with bacterial killing, such that if T>MIC was below 20% there was no effect on bacterial numbers in the lungs. As T>MIC increased, the response, in terms of decreased bacterial load, improved and at T>MICs of greater than 35 to 40% of the dosing interval, bacteriological cure was maximal. On the basis of equivalent T>MICs, these data would suggest that in humans a dosage of 500 mg three times daily (t.i.d.) should have efficacy equal to that of a dosage of 875 mg twice daily (b.i.d.). This hypothesis was evaluated in a rat model in which amoxicillin-clavulanate was given by computer-controlled intravenous infusion to achieve concentrations that approximate the concentrations achieved in the plasma of humans following oral administration of 500/125 mg t.i.d. or 875/125 mg b.i.d. Infusions continued for 3 days and bacterial numbers in the lungs 2 h after the cessation of the infusion were significantly reduced (P < 0.01) by both treatments in strains of S. pneumoniae for which amoxicillin MICs were below 2 microg/ml. When tested against a strain of S. pneumoniae for which the amoxicillin MIC was 4 microg/ml, the simulated 500/125-mg dose was ineffective but the 875/125-mg dose demonstrated a small but significant (P < 0. 01) reduction in bacterial numbers. These data confirm the findings in the mouse and indicate that amoxicillin-clavulanate administered at 875/125 mg b.i.d. would be as effective clinically as amoxicillin-clavulanate administered at 500/125 mg t.i.d.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Drug Therapy, Combination; Female; Mice; Microbial Sensitivity Tests; Models, Biological; Pneumococcal Infections; Pneumonia, Pneumococcal; Rats; Rats, Sprague-Dawley; Respiratory Tract Infections; Streptococcus pneumoniae

Topics: Adult; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cephalosporins; Community-Acquired Infections; Drug Therapy, Combination; Hospitalization; Humans; Penicillin G; Penicillin Resistance; Penicillins; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Radiography, Thoracic

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteria; beta-Lactamase Inhibitors; beta-Lactamases; Bronchitis; Colony Count, Microbial; Community-Acquired Infections; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Opportunistic Infections; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Respiratory Tract Infections; Streptococcus pneumoniae

Topics: Adult; Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Ampicillin Resistance; Anti-Bacterial Agents; Child, Preschool; Community-Acquired Infections; Drug Therapy, Combination; Haemophilus influenzae; Humans; Penicillin Resistance; Penicillins; Pneumonia, Bacterial; Pneumonia, Mycoplasma; Pneumonia, Pneumococcal; Pneumonia, Staphylococcal; Respiratory Tract Infections; Streptococcus pneumoniae

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Multivariate Analysis; Pneumonia, Pneumococcal; Streptococcus pneumoniae; Time Factors

In an attempt to determine the susceptibility breakpoints for amoxycillin, co-amoxiclav and cefotaxime in pneumococcal pneumonia, a neutropenic mouse model was established and tested with two strains having different susceptibility to penicillins and cefotaxime. With a penicillin-sensitive strain (MIC/MBC = 0.01/0.01 mg/L) the minimum dosage tested achieving significant cure was 2 mg/kg for amoxycillin, co-amoxiclav and cefotaxime. For the penicillin-insensitive strain (MIC/MBC = 1/2 mg/L), the minimum dosage tested giving significant cure was 50 mg/kg for amoxycillin and co-amoxiclav but 100 mg/kg for cefotaxime. Our results support the belief that MICs of amoxycillin, co-amoxiclav and cefotaxime for pneumococcal strains of < or = 0.5 or < or = 1 mg/L can be considered as clinically relevant susceptibility breakpoints.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Animals; Cefotaxime; Cephalosporins; Clavulanic Acids; Disease Models, Animal; Drug Therapy, Combination; Female; Mice; Microbial Sensitivity Tests; Penicillins; Pneumonia, Pneumococcal; Streptococcus pneumoniae

Resistance of microorganisms to antimicrobial agents is an increasing problem in the treatment of infectious diseases. In mixed infections, an interesting development can arise when one organism protects another from being killed by an antibiotic. Unfortunately, in the case of respiratory tract infections, experimental evidence of this development is poor. In this study, mice intranasally infected with a lethal number of pneumococci and treated with a curative dose of penicillin or amoxicillin died from pneumococcal pneumonia when they were coinoculated with beta-lactamase-producing Moraxella catarrhalis. beta-lactamase-negative M. catarrhalis did not show a similar indirect pathogenic effect. Treatment with a combination of amoxicillin and the beta-lactamase inhibitor clavulanic acid was not affected by beta-lactamase-producing M. catarrhalis. These findings help explain antibiotic failure in respiratory tract infections, even though the causative microorganism is sensitive to the antibiotic in vitro.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Animals; beta-Lactamases; Clavulanic Acids; Drug Therapy, Combination; Male; Mice; Mice, Inbred BALB C; Moraxella catarrhalis; Neisseriaceae Infections; Organ Specificity; Penicillin Resistance; Penicillins; Pneumonia, Pneumococcal; Streptococcus pneumoniae