Int J Antimicrob
Agents. 2005 Feb;25(2):110-9.
Efficacy of a new pharmacokinetically enhanced formulation of
amoxicillin/clavulanate (2000/125 mg) in adults with community-acquired
pneumonia caused by Streptococcus pneumoniae, including penicillin-resistant
strains.
File TM, Garau J, Jacobs MR, Wynne B, Twynholm M, Berkowitz E.
Summa Health System, 75 Arch Street, Akron, OH 44304, USA. filet@summa-health.org
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.
Ann Ital Med Int. 2004 Oct-Dec;19(4):276-9.
[Amoxicillin-clavulanic acid and oral anticoagulants: a possible
dangerous association]
[Article in Italian]
Cauli C, Fenu L, Perra A, Marongiu F.
Dipartimento di Scienze Mediche Internistiche, Universita degli Studi
di Cagliari, Policlinico Universitario di Monserrato, CA.
We describe a 68-year-old male patient, treated with amoxicillin-clavulanic
acid for 18 days and oral anticoagulants. He developed a cholestatic hepatitis
with conjugated bilirubin of 11 mg/dL and a concomitant overdose of oral
anticoagulants (INR 7). Nausea, vomiting, jaundice and large ecchymoses
occurred 41 days after treatment with amoxicillin-clavulanic acid; the
clinical manifestations resolved within 1 week and the liver tests returned
to normal 48 days after therapy withdrawal. The mechanism of the amoxicillin-clavulanate-induced
hepatitis is probably immunoallergic; this complication occurs mainly
in subjects with a metabolic and/or immunologic idiosyncrasy. The pharmacokinetics
of this antibiotic, which is not directly metabolized by cytochrome P450,
may be affected by the concomitant use of drugs under cytochrome P450
control. When using amoxicillin-clavulanic acid, one should take into
account its potential hepatic toxicity and possible interaction with oral
anticoagulants. However, it appears to be crucial to follow the correct
indications for both drugs. In fact, in the patient described above amoxicillin-clavulanic
acid was wrongly administered as prophylaxis after a cutaneous biopsy
of the nose. The same occurred with the oral anticoagulants prescribed
to the patient for a single episode of paroxysmal atrial fibrillation
which had occurred one year previously.
JAMA. 2005 Feb 23;293(8):949-55.
Amoxicillin-clavulanate vs ciprofloxacin for the treatment of
uncomplicated cystitis in women: a randomized trial.
Hooton TM, Scholes D, Gupta K, Stapleton AE, Roberts PL, Stamm
WE.
Department of Medicine, School of Medicine, University of Washington,
Seattle, USA. hooton@u.washington.edu
CONTEXT: The high prevalence of resistance to trimethoprim-sulfamethoxazole
and other antimicrobials among Escherichia coli causing acute cystitis
in women has led to increased use of alternative antibiotics. One such
antibiotic, amoxicillin-clavulanate, has not been well studied. OBJECTIVE:
To compare the efficacy of a 3-day regimen of amoxicillin-clavulanate
to that of a 3-day regimen of ciprofloxacin in the treatment of acute
cystitis in women. The primary study hypothesis was that the amoxicillin-clavulanate
and ciprofloxacin treatment groups would differ in clinical cure. DESIGN,
SETTING, AND PATIENTS: Randomized, single-blind treatment trial of 370
women, aged 18 to 45 years, with symptoms of acute uncomplicated cystitis
and a urine culture with at least 10(2) colony-forming units of uropathogens
per milliliter from a university student health center or a health maintenance
organization. INTERVENTIONS: Women were randomly assigned to receive amoxicillin-clavulanate
(500 mg/125 mg twice daily) or ciprofloxacin (250 mg twice daily) for
3 days and were followed up for 4 months. MAIN OUTCOME MEASURES: The main
outcome measure was clinical cure. Secondary study outcomes of interest
were microbiological cure and vaginal E coli colonization at the 2-week
follow-up visit. RESULTS: Clinical cure was observed in 93 (58%) of 160
women treated with amoxicillin-clavulanate compared with 124 (77%) of
162 women treated with ciprofloxacin (P<.001). Amoxicillin-clavulanate
was not as effective as ciprofloxacin even among women infected with strains
susceptible to amoxicillin-clavulanate (65 [60%] of 109 women in the amoxicillin-clavulanate
group vs 114 [77%] of 149 women in the ciprofloxacin group; P = .004).
The difference in clinical cure rates occurred almost entirely within
the first 2 weeks after therapy. Microbiological cure at 2 weeks was observed
in 118 (76%) of 156 women treated with amoxicillin-clavulanate compared
with 153 (95%) of 161 women treated with ciprofloxacin (P<.001). At
this visit, 45% of women in the amoxicillin-clavulanate group compared
with 10% in the ciprofloxacin group had vaginal colonization with E coli
(P<.001). CONCLUSIONS: A 3-day regimen of amoxicillin-clavulanate is
not as effective as ciprofloxacin for the treatment of acute uncomplicated
cystitis, even in women infected with susceptible strains. This difference
may be due to the inferior ability of amoxicillin-clavulanate to eradicate
vaginal E coli, facilitating early reinfection.
Eur J Obstet Gynecol Reprod Biol. 2005 Mar 1;119(1):21-6
Effect of amoxicillin sulbactam in threatened preterm labour with intact
membranes: a randomised controlled trial.
Keuchkerian SE, Sosa CG, Fernandez A, Alonso JG, Laborde A, Cuadro JC.
Department of Obstetrics and Gynecology, Pereira Rossell Hospital,
School of Medicine, University of Uruguay, Montevideo, Uruguay.
Objective: To determine whether treatment with amoxicillin-sulbactam in women with threatened idiopathic preterm labour will prolong the gestation and reduce preterm birth rates in a Latin-American population. Methods: A double-blind, placebo-controlled, randomized trial was conducted in 96 women who were hospitalized for preterm labour between 24 and 34 weeks of gestation at the Pereira Rossell Hospital, in Montevideo, Uruguay. The primary outcome measure was prematurity. The sample size was calculated a priori based on the hospital database. Statistical analyses were performed using the t-test, chi square, weighted mean difference (WMD) and relative risk (RR) with their confidence intervals (95% CI). Analysis by intention-to-treat. Results: Out of 47 patients assigned for antibiotics, 43 completed the treatment. There were no significant statistical differences between antibiotics and placebo group in prematurity (RR:1.04, 95% CI: 0.59, 1.84), prolongation of pregnancy (WMD:0.23, 95% CI: -0.96, 1.42) and other perinatal outcomes. Conclusion: Antibiotics did not prove to have benefits in improving perinatal outcomes in this Latin American population.
Antimicrob Agents Chemother. 2005 Mar;49(3):908-15.
Comparative bacteriological efficacy of pharmacokinetically enhanced
amoxicillin-clavulanate against Streptococcus pneumoniae with elevated
amoxicillin MICs and Haemophilus influenzae.
Berry V, Hoover J, Singley C, Woodnutt G.
GlaxoSmithKline, Collegeville, PA, USA.
A new pharmacokinetically enhanced formulation of amoxicillin-clavulanate
(2,000 mg of amoxicillin/125 mg of clavulanate twice a day; ratio 16:1)
has been designed, with sustained-release technology, to allow coverage
of bacterial strains with amoxicillin-clavulanic acid MICs of at least
4/2 mug/ml. The bacteriological efficacy of amoxicillin-clavulanate, 2,000/125
mg twice a day, ratio 16:1, was compared in a rat model of respiratory
tract infection versus four other amoxicillin-clavulanate formulations:
8:1 three times a day (1,000/125 mg), 7:1 three times a day (875/125 mg),
7:1 twice a day (875/125 mg), and 4:1 three times a day (500/125 mg);
levofloxacin (500 mg once a day); and azithromycin (1,000 mg on day 1
followed thereafter by 500 mg once a day). Bacterial strains included
Streptococcus pneumoniae, with amoxicillin-clavulanic acid MICs of 2/1
(one strain), 4/2, or 8/4 microg/ml (three strains each), and Haemophilus
influenzae, one beta-lactamase-positive strain and one beta-lactamase-negative,
ampicillin-resistant strain. Animals were infected by intrabronchial instillation.
Antibacterial treatment commenced 24 h postinfection, with doses delivered
by computer-controlled intravenous infusion to approximate the concentrations
achieved in human plasma following oral administration. Plasma concentrations
in the rat corresponded closely with target human concentrations for all
antimicrobials tested. Amoxicillin-clavulanate, 2,000/125 mg twice a day,
ratio 16:1, was effective against all S. pneumoniae strains tested, including
those with amoxicillin-clavulanic acid MICs of up to 8/4 microg/ml and
against beta-lactamase-producing and beta-lactamase-negative ampicillin-resistant
H. influenzae. These results demonstrate the bacteriological efficacy
of pharmacokinetically enhanced amoxicillin-clavulanate 2,000/125 mg twice
a day (ratio 16:1) against S. pneumoniae with amoxicillin-clavulanic acid
MICs of at least 4/2 microg/ml and support clavulanate 125 mg twice a
day as sufficient to protect against beta-lactamase in this rat model.
JAMA. 2005 Feb 23;293(8):949-55.
Amoxicillin-clavulanate vs ciprofloxacin for the treatment of
uncomplicated cystitis in women: a randomized trial.
Hooton TM, Scholes D, Gupta K, Stapleton AE, Roberts PL, Stamm WE.
Department of Medicine, School of Medicine, University of Washington,
Seattle, USA. hooton@u.washington.edu
CONTEXT: The high prevalence of resistance to trimethoprim-sulfamethoxazole
and other antimicrobials among Escherichia coli causing acute cystitis
in women has led to increased use of alternative antibiotics. One such
antibiotic, amoxicillin-clavulanate, has not been well studied. OBJECTIVE:
To compare the efficacy of a 3-day regimen of amoxicillin-clavulanate
to that of a 3-day regimen of ciprofloxacin in the treatment of acute
cystitis in women. The primary study hypothesis was that the amoxicillin-clavulanate
and ciprofloxacin treatment groups would differ in clinical cure. DESIGN,
SETTING, AND PATIENTS: Randomized, single-blind treatment trial of 370
women, aged 18 to 45 years, with symptoms of acute uncomplicated cystitis
and a urine culture with at least 10(2) colony-forming units of uropathogens
per milliliter from a university student health center or a health maintenance
organization. INTERVENTIONS: Women were randomly assigned to receive amoxicillin-clavulanate
(500 mg/125 mg twice daily) or ciprofloxacin (250 mg twice daily) for
3 days and were followed up for 4 months. MAIN OUTCOME MEASURES: The main
outcome measure was clinical cure. Secondary study outcomes of interest
were microbiological cure and vaginal E coli colonization at the 2-week
follow-up visit. RESULTS: Clinical cure was observed in 93 (58%) of 160
women treated with amoxicillin-clavulanate compared with 124 (77%) of
162 women treated with ciprofloxacin (P<.001). Amoxicillin-clavulanate
was not as effective as ciprofloxacin even among women infected with strains
susceptible to amoxicillin-clavulanate (65 [60%] of 109 women in the amoxicillin-clavulanate
group vs 114 [77%] of 149 women in the ciprofloxacin group; P = .004).
The difference in clinical cure rates occurred almost entirely within
the first 2 weeks after therapy. Microbiological cure at 2 weeks was observed
in 118 (76%) of 156 women treated with amoxicillin-clavulanate compared
with 153 (95%) of 161 women treated with ciprofloxacin (P<.001). At
this visit, 45% of women in the amoxicillin-clavulanate group compared
with 10% in the ciprofloxacin group had vaginal colonization with E coli
(P<.001). CONCLUSIONS: A 3-day regimen of amoxicillin-clavulanate is
not as effective as ciprofloxacin for the treatment of acute uncomplicated
cystitis, even in women infected with susceptible strains. This difference
may be due to the inferior ability of amoxicillin-clavulanate to eradicate
vaginal E coli, facilitating early reinfection.
Eur J Pediatr. 2004 Nov 10.
Treatment and outcome of severe and non-severe acute otitis media.
Hotomi M, Yamanaka N, Samukawa T, Suzumot M, Sakai A, Shimada
J, Ikeda Y, Faden H.
Department of Otolaryngology-Head and Neck Surgery, Wakayama Medical
University, Wakayama, Japan.
To determine outcomes in acute otitis media (AOM) according to severity
of disease and to assess different initial treatment regimens, 308 with
AOM were enrolled and divided into severe ( n=277; 89.9%) and non-severe
( n=31; 10.1%) groups based on symptoms and tympanic membrane changes.
Children in the severe group were initially managed with amoxicillin (AMPC)
whereas children in the non-severe group were initially managed without
antibiotics. Children were monitored on days 1, 5, 10, 14 and 28. Five
outcome measures were assessed: disappearance of symptoms at day 5, resolution
of tympanic membrane changes by day 28, disappearance of middle ear effusions
by day 28, recurrence of acute symptoms prior to day 28, and need to change
treatment regimens. Children with severe disease were more often male
(57% versus 36%, P<0.05) and more often colonized with pathogens (77%
versus 55%, P<0.05 than children with non-severe disease. The two groups
were similar with respect to age and day care attendance. Despite differences
in initial treatment regimens between the two groups, symptoms improved
at the same rate for severe and non-severe disease, 94% by day 5. In contrast,
tympanic membranes returned to normal in 69% of the severe and 81% of
the non-severe groups by day 28; however, as early as day 5, 10% of the
severe and 55% of the non-severe groups demonstrated normal tympanic membranes.
Middle ear effusions similarly disappeared more slowly in the severe group,
52% versus 74% by day 14 and 76% versus 84% by day 28. Recurrence rates
of acute symptoms occurred with equal frequency in the severe, 15%, and
non-severe groups, 10%. Failure of the symptoms or the tympanic membranes
to improve led to antibiotic changes in 59.9% of the severe group and
to the addition of antibiotics in 51.6% of the non-severe group. Children
in the severe group who failed to improve with an initial course of amoxicillin
were younger (40.2 months versus 45.8 months, P<0.05), had higher tympanic
membrane scores (4.5 versus 4.1, P<0.05), and were more often colonized
with penicillin-resistant Streptococcusp neumoniae (33.8% versus 6.5%,
P<0.01) than children who responded to AMPC. In a similar manner, children
with non-severe disease who failed to improve without antibiotics were
younger (40.7 months versus 54.8 months, P<0.05) and more often colonized
with pathogens (75.0% versus 33.4%, P<0.05). CONCLUSION:Severe disease
occurred more often among males and among children colonized with pathogens.
Response to treatment was impaired in younger children and in children
colonized with pathogens, especially penicillin-resistant Streptococcusp
neumoniae.
J Int Acad Periodontol. 2004 Oct;6(4 Suppl):143-9.
The microbiological case for adjunctive therapy for periodontitis.
Page RC.
Regional Clinical Dental Research Center, Health Sciences Bldg., Rm.
B-530, University of Washington, Seattle, WA 98195, USA.
That chronic periodontitis is an infectious disease is now firmly established, and the primary role of Porphyromonas gingivalis, Tannerella forsythensis and Treponema denticola is generally accepted. Treatment by mechanical means such as scaling and root planing or surgery generally results in significant clinical improvement but may not arrest the progress or recurrence of disease. Several studies have shown that the probability of achieving lasting stability as measured by the arrest of progressive attachment loss and bone loss by primary mechanical therapy is a function, in major part, of whether pathogenic microorganisms are still present at local subgingival sites at the completion of active therapy. The infecting bacterial species are susceptible to killing by several antibiotics including, among others, tetracycline-class drugs, amoxicillin and metronidazole as well as by local exposure to chlorhexidine. Randomized clinical trials have shown that use of systemically administered antibiotics as an adjunct to mechanical therapies significantly enhances clinical outcomes and stability. Several slow-release devices that deliver anti-microbial drugs directly into periodontal pockets have been developed and are now on the market. Use of these devices permits local delivery of long-lasting, high concentrations of doxycycline (Atridox) minocycline (Arestin), and chlorhexidine (PerioChip) directly into periodontal pockets. Although these devices differ with regard to ease of use, concentration of drug delivered and length of time high drug concentrations can be maintained, randomized clinical trials have shown that their use as an adjunctive treatment to scaling and root planing results in a significantly greater reduction of periodontal pocket depth and an average increase in clinical periodontal attachment level of about 0.8 mm. Gain in clinical attachment is greater in deeper pockets than in shallower pockets. Locally delivered adjunctive anti-microbial therapy is an effective means to enhance therapeutic outcomes.
Am J Manag Care. 2004 Oct;10(10):689-96.
Acute exacerbation of chronic bronchitis: a primary care consensus
guideline.
Brunton S, Carmichael BP, Colgan R, Feeney AS, Fendrick AM, Quintiliani
R, Scott G.
Department of Family Medicine, University of California, Irvine, Calif,
USA.
OBJECTIVE: To develop consensus on appropriate treatment for acute exacerbation of chronic bronchitis (AECB). CHARACTERISTICS AND ETIOLOGY: Patients with chronic bronchitis have an irreversible reduction in maximal airflow velocity and a productive cough on most days of the month for 3 months over 2 consecutive years. An AECB is characterized by a period of unstable lung function with worsening airflow and other symptoms. Most (80%) cases of AECB are due to infection, with half due to aerobic bacteria. The remaining 20% are due to noninfectious causes such as environmental factors or medication nonadherence. MANAGEMENT: Supportive care should be provided to all patients, which might include removal of irritants, use of a bronchodilator, oxygen, hydration, use of a systemic corticosteroid, and chest physical therapy. Antibacterial treatment should be reserved for patients with at least 1 key symptom (ie, increased dyspnea, sputum production, sputum purulence) and 1 risk factor (ie, age > or = 65 years, forced expiratory volume in 1 second < 50% of the predicted value, > or = 4 AECBs in 12 months, 1 or more comorbidities). A newer macrolide, extended-spectrum cephalosporin, or doxycycline is appropriate for an exacerbation of moderate severity, and high-dose amoxicillin/clavulanate or a respiratory fluoroquinolone should be used for a severe exacerbation. There has been increasing antibacterial resistance by the 3 most prevalent pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis). CONCLUSION: Although all AECB patients should receive supportive care, only patients with at least 1 key symptom and 1 risk factor should receive antibiotic therapy.
Antimicrob Agents Chemother. 2004 Nov;48(11):4144-7.
Effects of amoxicillin subinhibitory concentrations on the cross-protection
developed by pneumococcal antibodies in mouse sepsis caused by an amoxicillin-resistant
serotype 6B Streptococcus pneumoniae strain.
Tarrago D, Aguilar L, Gimenez MJ, Fenoll A, Casal J.
Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Ctra.
Majadahonda-Pozuelo Km.2, 28220 Majadahonda, Madrid, Spain.
A model of mouse sepsis caused by a serotype 6B Streptococcus pneumoniae strain (amoxicillin MIC of 8 microg/ml) was developed to investigate the therapeutic effect of an amoxicillin dose (3.12 mg/kg of body weight three times daily for 48 h) producing, over the whole treatment period, subinhibitory concentrations in serum (peak concentration [C(max)]: 6.1 microg/ml) in animals that prior to infection had been passively immunized with a 6B or 23F hyperimmune serum (obtained by immunization with a whole-cell heat-inactivated inoculum and diluted to produce no protective effect by itself). Mortality in nonimmunized animals treated with antibiotic (3.12 mg/kg) was 90%, and mortality in animals immunized but not treated with the antibiotic was 100%. Antibiotic treatment in immunized animals produced mortality rates </=20% when the hyperimmune serum was used, thus showing cross-protection and synergism (defined as the situation in which there is no response to the single agents [no differences versus placebo] while the combination exhibits significant activity) with subinhibitory concentrations of the antibiotic. The presence of antipneumococcal antibodies allowed antibiotic efficacy with negligible values of pharmacodynamic parameters (C(max)/MIC ratio of <1 and thus a null value for the time that serum levels exceed the MIC). This in vivo synergism offers a potential therapeutic strategy against resistant strains.
Arq Gastroenterol. 2004 Jan-Mar;41(1):71-6.
[Efficacy of the dosing regimen of pantoprazole 40 mg, amoxicillin
1000 mg and clarithromycin 500 mg, twice daily for 7 days, in the eradication
of Helicobacter pylori in patients with peptic ulcer]
[Article in Portuguese]
Coelho LG, Mattos AA, Francisconi CF, Castro Lde P, Andre SB.
Servico de Gastroenterologia, Nutricao, Cirurgia Geral e do Aparelho
Digestivo, Hospital das Clinicas, Universidade Federal de Minas Gerais,
Belo Horizonte, MG.
AIM: This is an open label, multicenter trial to determine the efficacy of the association of pantoprazole, clarithromycin and amoxicillin to eradicate Helicobacter pylori in patients with peptic ulcer. MATERIAL AND METHODS: Seventy-one patients (36 females, 35 males, average age 41.9 years) from three Brazilian university centers (located in the cities of Belo Horizonte and Porto Alegre), with peptic ulcers confirmed by endoscopy, and infections by H. pylori proven by at least two diagnostic testings were admitted in the trial. An association of pantoprazole 40 mg, clarithromycin 500 mg and amoxicillin 1.0 g was administered to patients twice daily for 7 days. RESULTS: By the end of treatment all patients were examined for digestive symptoms, presence of adverse events, and treatment adherence. Sixty days after the end of the treatment a new endoscopy with biopsies and respiratory function testing with 13C-urea breath test was performed in order to determine the eradication rates of that microorganism. Patients showing negative results at least in the 13C-urea breath test and in one other test (urease or histology) were considered H. pylori-negative. By the end of the trial, 60/69 (87%, CI 95% = 78.9-94.8) patients had the H. pylori eradicated in the per protocol analysis and 60/71 (84.5%, CI 95% = 76-92.9) in the intention-to-treat analysis. One patient was withdrawn from the trial due to a diarrhea. Twelve (16.9%) patients showed adverse symptoms that were deemed as mild symptoms. CONCLUSION: Our conclusion is that the association of pantoprazole, amoxicillin and clarithromycin administered during 7 days is an effective and well-tolerated alternative as regards the eradication of H. pylori in patients with peptic ulcer in Brazil.
Lancet. 2004 Sep 25;364(9440):1141-8.
Oral amoxicillin versus injectable penicillin for severe pneumonia
in children aged 3 to 59 months: a randomised multicentre equivalency
study.
Addo-Yobo E, Chisaka N, Hassan M, Hibberd P, Lozano JM, Jeena
P, MacLeod WB, Maulen I, Patel A, Qazi S, Thea DM, Nguyen NT.
BACKGROUND: Injectable penicillin is the recommended treatment for WHO-defined severe pneumonia (lower chest indrawing). If oral amoxicillin proves equally effective, it could reduce referral, admission, and treatment costs. We aimed to determine whether oral amoxicillin and parenteral penicillin were equivalent in the treatment of severe pneumonia in children aged 3-59 months. METHODS: This multicentre, randomised, open-label equivalency study was undertaken at tertiary-care centres in eight developing countries in Africa, Asia, and South America. Children aged 3-59 months with severe pneumonia were admitted for 48 h and, if symptoms improved, were discharged with a 5-day course of oral amoxicillin. 1702 children were randomly allocated to receive either oral amoxicillin (n=857) or parenteral penicillin (n=845) for 48 h. Follow-up assessments were done at 5 and 14 days after enrollment. Primary outcome was treatment failure (persistence of lower chest indrawing or new danger signs) at 48 h. Analyses were by intention-to-treat and per protocol. FINDINGS: Treatment failure was 19% in each group (161 patients, pencillin; 167 amoxillin; risk difference -0.4%; 95% CI -4.2 to 3.3) at 48 h. Infancy (age 3-11 months; odds ratio 2.72, 95% CI 1.95 to 3.79), very fast breathing (1.94, 1.42 to 2.65), and hypoxia (1.95, 1.34 to 2.82) at baseline predicted treatment failure by multivariate analysis. INTERPRETATION: Injectable penicillin and oral amoxicillin are equivalent for severe pneumonia treatment in controlled settings. Potential benefits of oral treatment include decreases in (1) risk of needle-borne infections; (2) need for referral or admission; (3) administration costs; and (4) costs to the family.
Pharmacoepidemiol Drug Saf. 2004 Jul 29;
Effectiveness of amoxicillin, azithromycin, cefprozil and clarithromycin
in the treatment of acute otitis media in children: a population-based
study.
Quach C, Collet JP, LeLorier J.
Infectious Diseases Division-MUHC: Montreal Children's Hospital, McGill
University, Montreal (QC), Canada.
Population-based studies may give results different from randomized clinical trials assessing the efficacy of antibiotics.OBJECTIVE: To determine the effectiveness of amoxicillin, azithromycin, cefprozil and clarithromycin in the treatment of acute otitis media (AOM) in children. METHODS: Using Quebec Health Insurance databases (RAMQ), we selected a cohort of children aged </=6 years, with a first episode of AOM between 1999 and 2002. The index AOM was defined as a medical service claim with a diagnosis of AOM and an antibiotic dispensation in the following 72 hours. Failures were defined as a new antibiotic dispensation, a hospitalization or outpatient visit for complications related to AOM in the 30 days after the index AOM. Data were analyzed using logistic regression. RESULTS: Overall, 12 693 failures occurred among 60 513 first episodes of AOM. Azithromycin was the only antibiotic that was associated with a decreased risk of failure overall, when compared to amoxicillin (OR 0.88, 95%CI: 0.82, 0.94). However in the first 3 days of treatment (n = 680), azithromycin was more associated with treatment failure (OR 1.6, 95%CI: 1.3, 2.0). Compared to amoxicillin, post-therapy failures (n = 9387) were more likely to occur with cefprozil (OR 1.2, 95%CI: 1.2, 1.3) but were less with azithromycin (OR 0.8 95%CI: 0.8, 0.9). CONCLUSIONS: Azithromycin had the lowest risk of failure 30 days after the onset of treatment but an increased risk of failure during the first few days of treatment. Amoxicillin remains an effective first-line drug for treating first AOM episodes.
Antimicrob Agents Chemother. 2004 Sep;48(9):3323-31.
Double-blind, randomized study of the efficacy and safety of oral
pharmacokinetically enhanced amoxicillin-clavulanate (2,000/125 milligrams)
versus those of amoxicillin-clavulanate (875/125 milligrams), both given
twice daily for 7 days, in treatment of bacterial community-acquired pneumonia
in adults.
File TM Jr, Lode H, Kurz H, Kozak R, Xie H, Berkowitz E; 600
Study Group.
Summa Health System, Akron, OH 44304, USA.
This randomized, double-blind, noninferiority trial was designed to demonstrate that pharmacokinetically enhanced amoxicillin-clavulanate (2,000/125 mg) was at least as effective clinically as amoxicillin-clavulanate 875/125 mg, both given twice daily for 7 days, in the treatment of community-acquired pneumonia in adults. In total, 633 clinically and radiologically confirmed community-acquired pneumonia patients (intent-to-treat population) were randomized to receive either oral amoxicillin-clavulanate 2,000/125 mg (n = 322) or oral amoxicillin-clavulanate 875/125 mg (n = 311). At screening, 160 of 633 (25.3%) patients had at least one typical pathogen isolated from expectorated or invasive sputum samples or blood culture (bacteriology intent-to-treat population). Streptococcus pneumoniae (58 of 160, 36.3%), methicillin-susceptible Staphylococcus aureus (34 of 160, 21.3%), and Haemophilus influenzae (33 of 160, 20.6%) were the most common typical causative pathogens isolated in both groups in the bacteriology intent-to-treat population. Clinical success in the clinical per protocol population at test of cure (days 16 to 37), the primary efficacy endpoint, was 90.3% (223 of 247) for amoxicillin-clavulanate 2,000/125 mg and 87.6% (198 of 226) for amoxicillin-clavulanate 875/125 mg (treatment difference, 2.7; 95% confidence interval, -3.0, 8.3). Bacteriological success at test of cure in the bacteriology per protocol population was 86.6% (58 of 67) for amoxicillin-clavulanate 2,000/125 mg and 78.4% (40 of 51) for amoxicillin-clavulanate 875/125 mg (treatment difference, 8.1%; 95% confidence interval, -5.8, 22.1). Both therapies were well tolerated. Amoxicillin-clavulanate 2,000/125 mg twice daily was shown to be as clinically effective as amoxicillin-clavulanate 875/125 mg twice daily for 7 days in the treatment of adult patients with community-acquired pneumonia, without a noted increase in the reported rate of adverse events.
Antimicrob Agents Chemother. 2004 Jul;48(7):2599-603.
Antibacterial effects of amoxicillin-clavulanate against Streptococcus
pneumoniae and Haemophilus influenzae strains for which MICs are high,
in an in vitro pharmacokinetic model.
MacGowan AP, Noel AR, Rogers CA, Bowker KE.
Bristol Centre for Antimicrobial Research & Evaluation, Department
of Medical Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol
BS10 5NB, United Kingdom.
The antibacterial effect of amoxicillin-clavulanate in two formulations, pharmacokinetically enhanced 16:1 amoxicillin-clavulanate twice a day (b.i.d.) and standard 7:1 amoxicillin-clavulanate b.i.d., were studied in an in vitro pharmacokinetic model of infection. Five strains of Streptococcus pneumoniae and two of Haemophilus influenzae, all associated with raised MICs (2 to 8 mg/liter), were used. The antibacterial effect was measured over 24 h by the area under the bacterial kill curve (AUBKC) and the log change in viable count at 24 h (Delta24). A high 10(8) CFU/ml and low 10(6) CFU/ml initial inocula were used. Employing the Delta24 effect measure, the time above MIC (T>MIC) 50% maximum effect (EC(50)) for S. pneumoniae was in the range 21 to 28% with an 80% maximal response of 41 to 51%, for the AUBKC measure, the value was 26 to 39%, irrespective of inoculum. For H. influenzae, the T>MIC EC(50) was 28 to 37%, and the 80% maximum response was 32 to 48% for the Delta24 measure and 20 to 48% for AUBKC. The maximum response occurred at a T>MIC of 50 to 60% for both species and inocula. The S. pneumoniae data were analyzed by analysis of variance to assess the effect of inoculum, formulation, and MIC on antibacterial effect. Standard and enhanced formulations had different effects depending on MIC, with the standard formulation less effective at higher amoxicillin-clavulanate MICs. This is explained by the greater T>MICs of the enhanced formulation. Although resistant to amoxicillin-clavulanate by conventional breakpoints, S. pneumoniae and H. influenzae strains for which MICs are 2 or 4 mg/liter may well respond to therapy with pharmacokinetically enhanced formulation amoxicillin-clavulanate.
