-
The Cochrane Database of Systematic... Sep 2010Asymptomatic bacteriuria occurs in 5% to 10% of pregnancies and, if left untreated, can lead to serious complications. (Review)
Review
BACKGROUND
Asymptomatic bacteriuria occurs in 5% to 10% of pregnancies and, if left untreated, can lead to serious complications.
OBJECTIVES
To assess which antibiotic is most effective and least harmful as initial treatment for asymptomatic bacteriuria in pregnancy.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2010) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomized controlled trials comparing two antibiotic regimens for treating asymptomatic bacteriuria.
DATA COLLECTION AND ANALYSIS
Review authors independently screened the studies for inclusion and extracted data.
MAIN RESULTS
We included five studies involving 1140 women with asymptomatic bacteriuria. We did not perform meta-analysis; each trial examined different antibiotic regimens and so we were not able to pool results. In a study comparing a single dose of fosfomycin trometamol 3 g with a five-day course of cefuroxime, there was no significant difference in persistent infection (risk ratio (RR) 1.36, 95% confidence interval (CI) 0.24 to 7.75), shift to other antibiotics (RR 0.08, 95% CI 0.00 to 1.45), or in allergy or pruritus (RR 2.73, 95% CI 0.11 to 65.24). A comparison of seven-day courses of 400 mg pivmecillinam versus 500 mg ampicillin, both given four times daily, showed no significant difference in persistent infection at two weeks or recurrent infection, but there was an increase in vomiting (RR 4.57, 95% CI 1.40 to 14.90) and women were more likely to stop treatment early with pivmecillinam (RR 8.82, 95% CI 1.16 to 66.95). When cephalexin 1 g versus Miraxid(R) (pivmecillinam 200 mg and pivampicillin 250 mg) were given twice-daily for three days, there was no significant difference in persistent or recurrent infection. A one- versus seven-day course of nitrofurantoin resulted in more persistent infection with the shorter course (RR 1.76, 95% CI 1.29 to 2.40), but no significant difference in symptomatic infection at two weeks, nausea, or preterm birth. Comparing cycloserine with sulphadimidine, no significant differences in symptomatic, persistent, or recurrent infections were noted.
AUTHORS' CONCLUSIONS
We cannot draw any definite conclusion on the most effective and safest antibiotic regimen for the initial treatment of asymptomatic bacteriuria in pregnancy. One study showed advantages with a longer course of nitrofurantoin, and another showed better tolerability with ampicillin compared with pivmecillinam; otherwise, there was no significant difference demonstrated between groups treated with different antibiotics. Given this lack of conclusive evidence, it may be useful for clinicians to consider factors such as cost, local availability and side effects in the selection of the best treatment option.
Topics: Anti-Bacterial Agents; Bacteriuria; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Randomized Controlled Trials as Topic
PubMed: 20824868
DOI: 10.1002/14651858.CD007855.pub2 -
Journal of the American Geriatrics... Mar 2010The syndrome of chronic obstructive pulmonary disease (COPD) consists of chronic bronchitis (CB), bronchiectasis, emphysema, and reversible airway disease that combine... (Review)
Review
The syndrome of chronic obstructive pulmonary disease (COPD) consists of chronic bronchitis (CB), bronchiectasis, emphysema, and reversible airway disease that combine uniquely in an individual patient. Older patients are at risk for COPD and its components--emphysema, CB, and bronchiectasis. Bacterial and viral infections play a role in acute exacerbations of COPD (AECOPD) and in acute exacerbations of CB (AECB) without features of COPD. Older patients are at risk for resistant bacterial organisms during their episodes of AECOPD and AECB. Organisms include the more-common bacteria implicated in AECOPD/AECB such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Less-common nonenteric, gram-negative organisms including Pseudomonas aeruginosa, gram-positive organisms including Staphylococcus aureus, and strains of nontuberculosis Mycobacteria are more often seen in AECOPD/AECB episodes involving elderly patients with frequent episodes of CB or those with bronchiectasis. Risk-stratified antibiotic treatment guidelines appear useful for purulent episodes of AECOPD and episodes of AECB. These guidelines have not been prospectively validated for the general population and especially not for the elderly population. Using a risk-stratification approach for elderly patients, first-line antibiotics (e.g., amoxicillin, ampicillin, pivampicillin, trimethoprim/sulfamethoxazole, and doxycycline), with a more-limited spectrum of antibacterial coverage, are used in patients who are likely to have a low probability of resistant organisms during AECOPD/AECB. Second-line antibiotics (e.g., amoxicillin/clavulanic acid, second- or third-generation cephalosporins, and respiratory fluoroquinolones) with a broader spectrum of coverage are reserved for patients with significant risk factors for resistant organisms and those who have failed initial antibiotic treatment.
Topics: Acute Disease; Age Factors; Aged; Anti-Bacterial Agents; Bacterial Infections; Bronchiectasis; Bronchitis, Chronic; Humans; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections
PubMed: 20398122
DOI: 10.1111/j.1532-5415.2010.02741.x -
BMJ Clinical Evidence Apr 2010Genital chlamydia is the most commonly reported bacterial sexually transmitted infection (STI) in developed countries. In women, infection occurs most commonly between... (Review)
Review
INTRODUCTION
Genital chlamydia is the most commonly reported bacterial sexually transmitted infection (STI) in developed countries. In women, infection occurs most commonly between the ages of 16 and 19 years.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of antibiotic treatment for men and non-pregnant women with uncomplicated genital chlamydial infection?What are the effects of antibiotic treatment for pregnant women with uncomplicated genital chlamydial infection? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 24 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: amoxicillin, ampicillin, azithromycin, ciprofloxacin, clarithromycin, clindamycin, doxycycline, erythromycin, lymecycline, minocycline, ofloxacin, pivampicillin, rifampicin, roxithromycin, sparfloxacin, tetracycline, and trovafloxacin.
Topics: Amoxicillin; Azithromycin; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Erythromycin; Humans
PubMed: 21718568
DOI: No ID Found -
Journal of Pharmaceutical Sciences Feb 2010Although prodrugging (prodrug derivatization) is a powerful technique for improving the pharmacokinetic characteristics of drugs, the intestinal pharmacokinetics of...
Although prodrugging (prodrug derivatization) is a powerful technique for improving the pharmacokinetic characteristics of drugs, the intestinal pharmacokinetics of prodrugs has yet to be elucidated fully. A previous article reported the kinetic requirement of prodrugs to overcome membrane barriers. In the present article, the luminal degradation of prodrugs was kinetically assessed to understand crucial factors in the intestinal absorption of prodrugs and to show a rational development procedure. A kinetic model equation involving luminal degradation clearance (CL(deg)) was derived, and CL(deg) was estimated according to the equation with in vitro and in vivo reported data of two kinds of ampicillin prodrugs (lenampicillin and pivampicillin) and one acyclovir prodrug (valacyclovir). For lenampicillin ((2,2-dimethyl-1-oxopropoxy)methyl ester derivative), CL(deg) was approximately 1.7 times as large as absorption clearance (CL(abs)), whereas for pivampicillin ((5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester derivative), CL(deg) was approximately one tenth of CL(abs). For valacyclovir (acyclovir prodrug), CL(deg) was negligible. These results indicate that not only membrane permeability but also luminal stability should be assessed for the rational development of orally effective prodrugs, and that luminal stabilization can improve the intestinal absorption of prodrugs. A procedure was proposed to develop orally effective prodrugs considered for luminal degradation as well as membrane permeability.
Topics: Acyclovir; Administration, Oral; Algorithms; Ampicillin; Anti-Bacterial Agents; Antiviral Agents; Drug Design; Intestinal Absorption; Models, Statistical; Permeability; Pivampicillin; Prodrugs; Valacyclovir; Valine
PubMed: 19623605
DOI: 10.1002/jps.21867 -
Canadian Family Physician Medecin de... Jan 2009To compare the effectiveness and toxicity of semisynthetic penicillins (SSPs) (amoxicillin, ampicillin, pivampicillin) and trimethoprim-based regimens (trimethoprim,... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To compare the effectiveness and toxicity of semisynthetic penicillins (SSPs) (amoxicillin, ampicillin, pivampicillin) and trimethoprim-based regimens (trimethoprim, trimethoprim-sulfamethoxazole, trimethoprim-sulfadiazine) in treating acute bacterial exacerbations of chronic bronchitis (ABECB).
DATA SOURCES
We searched MEDLINE, EMBASE, Current Contents, and the Cochrane Central Register of Controlled Trials to identify and extract data from relevant randomized controlled trials (RCTs).
STUDY SELECTION
Only RCTs comparing penicillins with trimethoprim-based regimens for the treatment of patients with ABECB that reported data on effectiveness, toxicity, or mortality were considered eligible for this meta-analysis.
SYNTHESIS
Out of 134 RCTs identified in the search, 5 RCTs involving 287 patients were included in the analysis. There were no differences between patients with ABECB treated with SSPs and those treated with trimethoprim, alone or in combination with a sulfonamide, in treatment success (intention-to-treat patients: n = 262, odds ratio [OR] 1.68, 95% confidence interval [CI] 0.91-3.09; clinically evaluable patients: n = 246, OR 1.59, 95% CI 0.79-3.20) or number of drug-related adverse events in general (n = 186 patients, OR 0.37, 95% CI 0.11-1.24), frequency of diarrhea or skin rashes, or number of withdrawals due to adverse events (n = 179 patients, OR 0.27, 95% CI 0.07-1.03).
CONCLUSION
Based on limited evidence leading to wide CIs of the estimated treatment effects, SSPs and trimethoprim-based regimens seem to be equivalent in terms of effectiveness and toxicity for ABECB.
Topics: Acute Disease; Amoxicillin; Anti-Infective Agents; Bronchitis, Chronic; Drug Therapy, Combination; Humans; Pivampicillin; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 19155372
DOI: No ID Found -
BMJ Clinical Evidence Jun 2008Genital chlamydia is the most commonly reported bacterial sexually transmitted disease (STD) in resource-rich countries. In women, infection occurs most commonly between... (Review)
Review
INTRODUCTION
Genital chlamydia is the most commonly reported bacterial sexually transmitted disease (STD) in resource-rich countries. In women, infection occurs most commonly between the ages of 16 and 19 years.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of antibiotic treatment in men, non-pregnant women, and pregnant women with uncomplicated genital chlamydia infection? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 24 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: amoxicillin, ampicillin, azithromycin, ciprofloxacin, clarithromycin, clindamycin, doxycycline, erythromycin, lymecycline, minocycline, ofloxacin, pivampicillin, rifampicin, roxithromycin, sparfloxacin, tetracycline, and trovafloxacin.
Topics: Amoxicillin; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Doxycycline; Erythromycin; Humans
PubMed: 19450291
DOI: No ID Found -
Biological & Pharmaceutical Bulletin Jul 2007Bacampicillin was developed as a prodrug to improve the intestinal absorption of its metabolite ampicillin. This study was undertaken to characterize bacampicillin...
Bacampicillin was developed as a prodrug to improve the intestinal absorption of its metabolite ampicillin. This study was undertaken to characterize bacampicillin transport in Caco-2 cells. The uptake of bacampicillin in Caco-2 cells was significantly greater than those of ampicillin and pivampicillin. An Eadie-Hofstee plot obtained from 5-min uptake of 0.2-5 mM bacampicillin was linear, indicating the presence of a saturable transport system for bacampicillin with K(m) and V(max) of 3.6 mM and 23.9 nmol/mg protein/min, respectively. Hydrophilic organic cations such as choline, cimetidine, guanidine, nicotinamide, 1-methylnicotiamide, and tetraethylammonium failed to modulate bacampicillin uptake in Caco-2 cells whereas diphenhydramine, procainamide, and thiamine significantly depressed it. Moreover, when thiamine was preloaded in Caco-2 cells, bacampicillin uptake was significantly increased, indicating that this cationic vitamin was capable of trans-stimulating bacampicillin transport across the apical membrane of Caco-2 cells. However, trans-stimulated bacampicillin uptake was not observed in the presence of diphenhydramine. Bacampicillin uptake increased with elevation of the medium pH, and the known modulators of thiamine transport such as amiloride and oxythiamine significantly inhibited bacampicillin uptake. Thiamine also significantly decreased the apical-to-basolateral transport of bacampicillin across Caco-2 cell monolayers. However, thiamine did not exert any modulating effect on pivampicillin uptake and its apical-to-basolateral permeation in Caco-2 cells. These results suggest that bacampicillin is transported in Caco-2 cells, sharing a carrier-mediated system with thiamine.
Topics: Ampicillin; Anti-Bacterial Agents; Biological Transport; Caco-2 Cells; Diphenhydramine; Humans; Hydrogen-Ion Concentration; Membrane Transport Proteins; Peptide Transporter 1; Pivampicillin; Symporters; Thiamine
PubMed: 17603179
DOI: 10.1248/bpb.30.1344 -
Chest Aug 2007Although acute exacerbations of chronic bronchitis (AECBs) are common, there has been no metaanalysis that focused on the optimum regimen. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although acute exacerbations of chronic bronchitis (AECBs) are common, there has been no metaanalysis that focused on the optimum regimen.
METHODS
To evaluate the comparative effectiveness and safety of first-line antimicrobial agents (ie, amoxicillin, ampicillin, pivampicillin, trimethoprim/sulfamethoxazole, and doxycycline) and second-line antimicrobial agents (ie, amoxicillin/clavulanic acid, macrolides, second-generation or third-generation cephalosporins, and quinolones) for the treatment of patients with AECB, in an era of increasing antimicrobial resistance among the microbes responsible for AECB, we performed a metaanalysis of randomized controlled trials (RCTs) retrieved through searches of the PubMed and the Cochrane databases.
RESULTS
Twelve RCTs were included in the metaanalysis. First-line antibiotics were associated with lower treatment success compared to second-line antibiotics in the clinically evaluable patients (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.34 to 0.75). There were no differences among the compared regimens regarding mortality (OR, 0.64; 95% CI, 0.25 to 1.66) or treatment success (OR, 0.56; 95% CI, 0.22 to 1.43) in microbiologically evaluable patients, or adverse effects in general (OR, 0.75; 95% CI, 0.39 to 1.45) or diarrhea in particular (OR, 1.58; 95% CI, 0.74 to 3.35).
CONCLUSIONS
Compared to first-line antibiotics, second-line antibiotics are more effective, but not less safe, when administered to patients with AECB. The available data did not allow for stratified analyses according to the presence of risk factors for poor outcome, such as increased age, impaired lung function, airway obstruction, and frequency of exacerbations; this fact should be taken into consideration when interpreting the findings of this metaanalysis.
Topics: Bronchitis, Chronic; Confidence Intervals; Humans; Macrolides; Odds Ratio; Penicillins; Randomized Controlled Trials as Topic; Recurrence; Treatment Outcome
PubMed: 17573508
DOI: 10.1378/chest.07-0149 -
Drugs in R&D 2006Carnitine is a naturally occurring compound that is essential in energy metabolism of the mammalian heart. In addition to its essential role in facilitating... (Review)
Review
Carnitine is a naturally occurring compound that is essential in energy metabolism of the mammalian heart. In addition to its essential role in facilitating beta-oxidation, carnitine eliminates excess toxic acyl residues and regulates the mitochondrial acetyl coenzyme A (CoA)/CoA ratio. Thus, it is not surprising that patients with carnitine deficiency syndromes exhibit defects in energy metabolism and in some cases demonstrate left ventricular dysfunction. Pivalic acid is commonly used to create prodrugs, such as pivampicillin and pivmecillinam, to facilitate enteral absorption and increase oral bioavailability. Pivalic acid released from the drug following absorption readily forms an ester with carnitine, which is then excreted as pivaloylcarnitine. Sustained loss of carnitine in the form of this ester induces a state of carnitine deficiency, exemplified by low plasma and tissue carnitine content. This review examines the effects in the rat of short- and long-term sodium pivalate treatment on: (1) cardiac carnitine content; (2) in vitro mechanical function; (3) markers of glycolytic and fatty acid metabolism; and (4) energy substrate metabolism. Treatment with sodium pivalate induces a gradual loss of cardiac carnitine content for up to 12 weeks. Doubling the duration of treatment is not associated with any further decrease in cardiac carnitine content. While heart function following short-term treatment (2 weeks) is normal under aerobic conditions, impaired recovery of function following ischaemia is seen. In contrast, long-term treatment (11-28 weeks) is associated with impaired heart function, which is dependent on workload and substrate availability. Impaired heart function is also associated with reductions in activity of 3-hydroxyacyl CoA dehydrogenase and rates of fatty acid oxidation. However, to maintain adenosine triphosphate production, glucose metabolism, expressed as hexokinase activity and glucose oxidation, is increased in carnitine-deficient hearts. Hearts from sodium pivalate-treated animals demonstrate a cardiomyopathy that is dependent on duration of treatment, workload and substrate supply. This model of hypocarnitinaemia may thus be useful to study the metabolic and cardiac consequences of carnitine-deficiency syndromes.
Topics: Animals; Carnitine; Energy Metabolism; Models, Animal; Myocardium; Pentanoic Acids; Rats; Ventricular Dysfunction, Left
PubMed: 16752941
DOI: 10.2165/00126839-200607030-00002 -
Antimicrobial Agents and Chemotherapy Apr 2005Pivampicillin (PIVA), an acyloxymethylester of ampicillin, is thought to enhance the oral bioavailability of ampicillin because of its greater lipophilicity compared to...
Pivampicillin (PIVA), an acyloxymethylester of ampicillin, is thought to enhance the oral bioavailability of ampicillin because of its greater lipophilicity compared to that of ampicillin. The fate of PIVA in intestinal cells and the exact location of its conversion into ampicillin have, however, never been unambiguously established. Polarized Caco-2 cells have been used to examine the handling of PIVA and the release of ampicillin from PIVA by the intestinal epithelium. Experiments were limited to 3 h. Cells incubated with PIVA (apical pole) showed a fast accumulation of ampicillin and transport toward the basolateral medium, whereas PIVA itself was only poorly accumulated and transported. Cells incubated with free ampicillin accumulated and transported only minimal amounts of this drug. Release of ampicillin from cells incubated with PIVA was unaffected by PEPT1 and OCTN2 inhibitors but was sharply decreased after ATP depletion or addition of bis(4-nitrophenyl)-phosphate (BNPP; an esterase inhibitor). PIVA incubated with Caco-2 lysates released free ampicillin, and this release was inhibited by BNPP. Efflux studies showed that the ampicillin that accumulated in cells after incubation with PIVA was preferentially transported out of the cells through the basolateral pole. This efflux was decreased by multidrug resistance-associated protein (MRP) inhibitors (probenecid, MK-571) and by ATP depletion. A phthalimidomethylester of ampicillin that resists cellular esterases failed to cause any significant release (cell lysate) or transport (polarized Caco-2 cells) of ampicillin. These results show that when PIVA is given to Caco-2 cells from their apical pole, ampicillin is released intracellularly and that ampicillin is thereafter preferentially effluxed into the basolateral medium through an MRP-like transporter.
Topics: Ampicillin; Anti-Bacterial Agents; Biological Transport; Caco-2 Cells; Cell Polarity; Colon; Humans; Pivampicillin; Prodrugs
PubMed: 15793098
DOI: 10.1128/AAC.49.4.1279-1288.2005