amoxicillin-potassium-clavulanate-combination and Haemophilus-Infections

Double tympanocentesis studies of children with acute otitis media, carried out over an 11-year period, were used to confirm that pharmacokinetic (PK) and pharmacodynamic (PD) parameters can be used as predictors of the bacteriological and clinical efficacy of antimicrobial agents. Predicted susceptibilities of common respiratory pathogens, such as Streptococcus pneumoniae and Haemophilus influenzae, were compared with the bacteriological outcome of treatment in which the high-dose formulation of amoxicillin/clavulanate (90mg/kg/day) given twice daily achieved the greatest bacteriological eradication rates for an oral agent. Further analysis of the data has indicated that failure to eradicate bacteria from the middle ear fluid is strongly correlated with clinical failure.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae; Treatment Outcome

Evidence from studies in otitis media indicates that antimicrobials and dosing regimens that have equivalent bacteriologic efficacy against susceptible pathogens can have significantly different bacteriologic success rates against resistant strains of the same species. Unlike macrolide and fluoroquinolone resistance, penicillin resistance can be overcome in Streptococcus pneumoniae by increasing the dose, and hence increasing the time for which the serum concentrations are above the MIC. The new clinical formulation of extra-strength amoxicillin-clavulanate provides 90 mg/kg per day amoxicillin plus 6.4 mg/kg per day clavulanate (14:1) divided every 12 h, compared with 45/6.4 mg/kg per day b.i.d. with conventional dosing. The pharmacokinetic/pharmacodynamic (PK/PD) profiles of extra-strength amoxicillin-clavulanate predict that the new formulation will be more effective than the conventional formulation against S. pneumoniae with elevated amoxicillin MICs and against Haemophilus influenzae. In an open-label, non-comparative study in children with acute otitis media, the extra-strength formulation had high bacteriologic success rates against the major respiratory pathogens, including penicillin-resistant S. pneumoniae. The development of new antimicrobial agents and formulations should be aimed at meeting PK/PD parameters predictive of bacterial eradication of both susceptible and resistant strains.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Area Under Curve; Child; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae; Treatment Failure

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

Topics: Amoxicillin-Potassium Clavulanate Combination; Bacterial Capsules; Cephalosporins; Drug Resistance, Microbial; Drug Therapy, Combination; Genes, Bacterial; Haemophilus Infections; Haemophilus influenzae; Haemophilus Vaccines; Humans; Meningitis; Polysaccharides, Bacterial; Serotyping; Vaccines, Conjugate; Virulence

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

Decreased susceptibility of pathogens to currently used agents for recurrent otitis media has provided the impetus for identifying new antimicrobial options.. To compare gatifloxacin with amoxicillin/clavulanate in children with recurrent or nonresponsive acute otitis media (AOM).. Included in this multicenter randomized trial were 413 patients, ranging in age from 6 months to 7 years, who had recurrent AOM (at least 3 episodes in the previous 6 months or 4 episodes in the previous 12 months) and/or had failed antibiotic therapy for AOM within 14 days of enrollment. Diagnosis required evidence of acute inflammation and otoscopic findings of middle ear effusion; baseline tympanocentesis was optional and encouraged. Children were randomly assigned (2:1) to 10 days of oral therapy with gatifloxacin suspension (10 mg/kg of body weight once daily) or amoxicillin/clavulanate suspension (45/6.4 mg/kg/d in 2 divided doses).. : Clinical cure was obtained in 90.2% (222 of 246) of patients in the gatifloxacin group and 84.3% (102 of 121) of those in the amoxicillin/clavulanate group (95% confidence interval, -1.9-12.9) 3-10 days after treatment ended. Gatifloxacin was associated with higher clinical cure rates than was amoxicillin/clavulanate in children younger than 2 years of age (92.0% versus 80.0%, respectively). Cure rates by pretreatment pathogen in the gatifloxacin and amoxicillin/clavulanate groups were 92.1% (35 of 38) versus 88.9% (16 of 18) for Streptococcus pneumoniae infections and 88.2% (30 of 34) versus 92.3% (12 of 13) for Haemophilus influenzae infections, respectively. Sustained clinical cures 3-4 weeks after treatment ended were obtained in 74.4% (183 of 246) of patients treated with gatifloxacin and 72.7% (88 of 121) of those treated with amoxicillin/clavulanate. Adverse events considered drug-related occurred with similar frequency in the 2 groups. Six patients (2.2%) in the gatifloxacin group and 2 patients (1.5%) in the amoxicillin/clavulanate group developed transient symptoms of mild or moderate arthralgia.. In this comparative evaluation of fluoroquinolone therapy in children with AOM, gatifloxacin was similar in clinical efficacy to amoxicillin/clavulanate 45/6.4 mg/kg/d for treatment of recurrent/nonresponsive infections.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Infective Agents; Child; Child, Preschool; Female; Fluoroquinolones; Gatifloxacin; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Otitis Media; Pneumococcal Infections; Recurrence; Single-Blind Method; Streptococcus pneumoniae; Treatment Failure; Treatment Outcome

Recurrent otitis media and acute otitis media treatment failure are commonly encountered in the pediatric population.. To compare the clinical efficacy of gatifloxacin with amoxicillin/clavulanate for the treatment of acute otitis media treatment failure and recurrent otitis media.. Three hundred fifty-four children 6 months-7 years with recurrent otitis media and/or acute otitis media failure were stratified according to age (younger than 2 years versus 2 years or older) and then randomly assigned to 10 days of treatment with gatifloxacin 10 mg/kg once daily or amoxicillin/clavulanate 90 mg/6.4 mg in 2 divided doses. Tympanocentesis was performed in 116 children with acute otitis media treatment failure and 52 with recurrent otitis media at study entry to validate the clinical diagnosis and provide microbiologic data. The primary outcome measure was clinical resolution of infection at the test-of-cure visit 3-10 days after completing treatment.. Clinical resolution of acute otitis media was observed in 79.0% (49 of 62) of clinically evaluable children younger than 2 years and 90.3% (56 of 62) of those 2 years or older who were treated with gatifloxacin as compared with 77.6% (45 of 58) of children younger than 2 years and 79.7% (47 of 59) of children 2 years or older treated with amoxicillin/clavulanate. In patients with acute otitis media treatment failure, clinical response rates for children younger than 2 years and those 2 years or older were 87.5% (21 of 24) and 97.0% (32 of 33) with gatifloxacin versus 63.6% (14 of 22) and 83.9% (26 of 31) with amoxicillin/clavulanate. The corresponding clinical response rates in patients with recurrent otitis media were 79.2% (19 of 24) and 85.7% (18 of 21) with gatifloxacin and 90.5% (19 of 21) and 76.0% (19 of 25) with amoxicillin/clavulanate. Clinical success in those subjects having pretreatment middle ear fluid pathogens was similar for the 2 regimens [80.0% (24 of 30) gatifloxacin, 77.1% (27 of 35) amoxicillin/clavulanate]. Emergence of fluoroquinolone-resistant strains was not observed. Both drugs were generally well-tolerated. Diarrhea was the most common drug-related adverse event (10% gatifloxacin, 18% amoxicillin/clavulanate). No evidence of abnormal joint or gait findings was found during a 12-month follow-up.. Gatifloxacin once daily is at least as effective and well-tolerated as amoxicillin/clavulanate twice daily in children with acute otitis media treatment failure or recurrent otitis media. There was no evidence of arthrotoxicity or emergence of fluoroquinolone-resistant bacteria in gatifloxacin-treated children.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Infective Agents; Child; Child, Preschool; Female; Fluoroquinolones; Gatifloxacin; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Otitis Media; Pneumococcal Infections; Recurrence; Single-Blind Method; Streptococcus pneumoniae; Treatment Failure; Treatment Outcome

Streptococcus pneumoniae (Sp) and Haemophilus influenzae (Hi) are the leading bacterial cause of acute otitis media (AOM), having the nasopharynx (NP) as their reservoir. In October 2001 we began a prospective, multicenter, randomized, evaluator blind study, comparing the efficacy of amoxicillin-sulbactam (Ax/S) and amoxicillin-clavulanic acid (Ax/C) for the treatment of non-recurrent AOM (nr-AOM). Both antimicrobial susceptibility (AS) to Ax/S and Ax/C from Sp and Hi carried by study children (aged 6-48 months with nr-AOM) and, clinical outcome after treatment with high dose of either Ax/C (7:1) or Ax/S (4:1) (amoxicillin dose: 80 mg/(kg day), b.i.d. for 10 days) were assessed. Nasal cultures (NCs) were taken at Day 0. Follow-up NCs, were done only for Sp carriers. On final analysis 247/289 pts (85.5%) were fully evaluable (120 Ax/S and 127 Ax/C). NP carriage rate of Hi and Sp at Day 0 was 32.2% (93/289 pts) and 28.7% (83/289 pts), respectively. Persistent Sp carriage was detected only in 2 pts. Hi betalactamase positive rate was 13% (12/93). MICs for Ax/S and Ax/C were identical when tested against Sp and Hi isolates (range < or = 0.016-1.0 and < or = 0.016-0.25 mg/L, respectively). Clinical efficacy at Days 12-14 and 28-42 were 98.3% (115/117) and 94.2% (97/103) for Ax/S; and 98.3% (115/117) and 95.1% (98/103) for Ax/C, respectively (pNS). We conclude, that Sp and Hi isolated from NCs of nr-AOM pts were highly sensitive to both drugs and correlated with high clinical efficacy rate.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Argentina; Carrier State; Child, Preschool; Drug Administration Schedule; Drug Combinations; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Otitis Media; Pneumococcal Infections; Prospective Studies; Single-Blind Method; Streptococcus pneumoniae; Sulbactam; Treatment Outcome

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Drug Administration Schedule; Haemophilus Infections; Haemophilus influenzae; Humans; Maxillary Sinusitis; Radiography; Streptococcal Infections; Streptococcus pneumoniae; Streptococcus pyogenes

The role of routine antimicrobial treatment of acute middle-ear infections is under debate, because the efficacy of antimicrobials in the resolution of middle-ear fluid has not been unambiguously proven. Acute tube otorrhea is regarded as evidence of acute otitis media, and for methodologic reasons it was chosen to provide objectivity for diagnostics and outcome assessment. The objective of this study was to assess whether amoxicillin-clavulanate accelerates the resolution of acute tube otorrhea.. Randomized, double-blind, placebo-controlled study in outpatient setting.. Volunteer sample of basically healthy 6- to 72-month-old children with a tympanostomy tube. Eligibility required having acute tube otorrhea of <48 hours' of duration and no prior treatment within the last 2 weeks. The mean age of the participants was 25 months; they had a history of 3 episodes of acute otitis media (median), and 99% had manifestations of a concomitant respiratory infection. Of 79 randomized patients, 7 were withdrawn because of adverse events; 66 patients completed the study.. Amoxicillin-clavulanate (N = 34; 45 mg/kg/d) or matching placebo (N = 32) for 7 days and daily suction of middle-ear fluid through tympanostomy tube.. Duration of acute tube otorrhea and duration of bacterial growth in middle-ear fluid.. The median duration of tube otorrhea was significantly shorter in amoxicillin-clavulanate than in the placebo group (3 vs 8 days). At the end of the 7-day medication period, tube otorrhea was resolved in 28 of 34 children receiving amoxicillin-clavulanate compared with 13 of 32 children on placebo (treatment-control difference 41%; 95% confidence interval, 20%-63%; number needed to treat, 2.4). The median duration of bacterial growth in middle-ear fluid was shorter in amoxicillin-clavulanate than in the placebo group (1 vs 8 days).. Oral antibiotic treatment significantly accelerates the resolution of acute tube otorrhea by reducing bacterial growth in middle-ear fluid.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Middle Ear Ventilation; Moraxella catarrhalis; Otitis Media, Suppurative; Pneumococcal Infections; Streptococcus pneumoniae

Topics: Acute Disease; Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Maxillary Sinusitis; Middle Aged; Pneumococcal Infections; Treatment Outcome

In an open, randomized study of 60 patients with acute or recurrent sinusitis, the bacteriological and clinical efficacy of roxithromycin 150 mg bd were compared with those of po co-amoxiclav (625 mg) tds. Of 52 patients who underwent sinus puncture for isolation of causative organisms, 48 had pathogens sensitive to both antibiotics. Satisfactory clinical response was obtained in 93.1% (27/29) evaluable patients receiving roxithromycin and 88.8% (24/27) receiving co-amoxiclav. Tolerability was significantly better in the roxithromycin group, with 1/29 (3.4%) patients in this group experiencing gastrointestinal side-effects, compared with 7/27 (25.9%) patients in the co-amoxiclav group (P < 0.05). Although the study had limited power to detect differences, roxithromycin demonstrated clinical, bacteriological and overall efficacy similar to that of co-amoxiclav, but with better tolerability. Roxithromycin thus appears to be an effective and well-tolerated drug for the treatment of acute and recurrent sinusitis.

Topics: Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteroides fragilis; Bacteroides Infections; Drug Therapy, Combination; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Middle Aged; Moraxella catarrhalis; Neisseriaceae Infections; Pneumococcal Infections; Roxithromycin; Sinusitis; Staphylococcal Infections; Streptococcus pneumoniae

Treatments with once-daily trovafloxacin (200 or 100 mg) and amoxicillin/clavulanic acid (500/125 mg three times daily) were compared in adults with acute exacerbations of chronic obstructive bronchitis. At end of treatment, 95% (113/119) of clinically evaluable patients receiving trovafloxacin 200 mg, 98% (113/115) of patients treated with trovafloxacin 100 mg and 97% (113/117) of patients receiving amoxicillin/clavulanic acid were cured or improved. At study end, 91%, 87% and 88%, respectively, were cured or improved. At end of treatment, trovafloxacin 200 mg eradicated Haemophilus influenzae in 97% of patients, Streptococcus pneumoniae in 90% and Chlamydia pneumoniae in 100%. The respective eradication rates for trovafloxacin 100 mg were 84%, 100% and 100%; those for amoxicillin/clavulanic acid were 92%, 100% and 100%. At study end, trovafloxacin 200 mg totally eradicated all three pathogens. Trovafloxacin 100 mg eradicated Haemophilus influenzae in 91% of patients, Streptococcus pneumoniae in 100% and Chlamydia pneumoniae in 80%. Respective eradication rates for amoxicillin/clavulanic acid were 78%, 100% and 80%. Only 7% (10/144) of patients receiving trovafloxacin 200 mg reported treatment-related adverse events, as did 7% (10/135) of patients given trovafloxacin 100 mg and 12% (17/140) of patients given amoxicillin/clavulanic acid.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Infective Agents; Bronchitis; Chlamydia Infections; Chronic Disease; Drug Therapy, Combination; Female; Fluoroquinolones; Haemophilus Infections; Humans; Male; Middle Aged; Naphthyridines; Pneumococcal Infections

Upper-respiratory-tract infection is one of the main causes of overuse of antibiotics. We have found previously that bacteria such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae can be isolated from the nasopharyngeal secretions of a substantial proportion of adults with upper-respiratory-tract infections. We have assessed the efficacy of co-amoxiclav in patients with common colds but no clinical signs of sinusitis or other indications for antibiotics.. Between January, 1992 and March, 1994, 314 patients who presented to our outpatient clinic with common colds were enrolled in the double-blind, placebo-controlled study. They were randomly assigned 5 days' treatment with co-amoxiclav (375 mg three times daily) or identical placebo. Clinical examinations were done at enrolment and on day 5-7 to assess outcome (cured, persistent symptoms, worse symptoms). Seven patients were excluded after randomisation, seven did not have nasopharyngeal aspiration, and 12 did not return for followup assessment.. Of 300 patients with nasopharyngeal aspirates, 72 had negative bacterial cultures, 167 had cultures positive only for bacteria unrelated to respiratory infections, and 61 had cultures positive for H influenzae, M catarrhalis, or S pneumoniae. At 5-day follow-up of these culture-positive patients, the distribution of outcome was significantly better among co-amoxiclav-treated (n=30) than placebo-treated (n=28) patients (cured 27 vs 4%; persistent symptoms 70 vs 60%; worse symptoms 3 vs 36%; p=0.001). Patients on co-amoxiclav also scored their symptoms significantly lower than patients on placebo (p=0.008). Among culture-negative patients (n=230), the outcome distribution did not differ between the treatment groups (p=0.392).. The majority of patients with upper-respiratory-tract infection do not benefit from antibiotics and side-effects are frequent. However, for the subgroup whose nasopharyngeal secretions contain H influenzae, M catarrhalis, or S pneumoniae, antibiotics are clinically beneficial.

Topics: Adult; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Bacterial Infections; Clavulanic Acids; Common Cold; Double-Blind Method; Drug Therapy, Combination; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Moraxella catarrhalis; Nasopharynx; Neisseriaceae Infections; Pneumococcal Infections; Treatment Outcome

In this open comparative and prospective study 180 adults of either sex were randomised to treatment with either amoxicillin/clavulanic acid (AMC) 500/125mg tid or cefetamet pivoxil (CAT) 500mg bid for 7 days. Demographic data and assessable findings were similar in both groups. Clinical outcomes of 169 assessable patients showed high efficacy of both drugs: 92% with AMC and 96% with CAT. Bacteriological response rates were equivalent in 141 evaluable cases: 84% vs. 89%, respectively. Baseline susceptibility testing (DIN) revealed a notable number of Haemophilus species either intermediately susceptible or resistant to AMC. Gastrointestinal disorders predominated among the adverse events with diarrhea occurring nearly twice as often in the AMC group. CAT is an effective and safe alternative option in the treatment of AECB in adults. The advantage of CAT is its enhanced activity against gram-negative bacteria. It is well tolerated.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Bronchitis; Ceftizoxime; Cephalosporins; Chronic Disease; Clavulanic Acids; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies

Cefprozil is a new oral cephalosporin with activity against the most common pathogens isolated in acute otitis media. This randomized study enrolled 361 patients (mean age 29 months). Physical examination and culture via tympanocentesis were required less than 48 h before therapy. One hundred and ninety-one patients were evaluable for clinical efficacy; 99 received cefprozil (20 mg/kg/day bd) and 92 received amoxycillin/clavulanate (13.3 mg/kg/day tid). Duration of treatment was 7-9 days for 81 patients, 10 days for 105 patients and 11-16 days for five patients. The treatment groups were comparable with respect to demographics, severity of infection and number of previous episodes. Clinical evaluations of efficacy were based on physical examination including otoscopy within a 14 day period after therapy. Satisfactory clinical responses were achieved in 84% of cefprozil-treated patients and 87% of amoxycillin/clavulanate-treated patients. Pathogens most commonly isolated included Haemophilus influenzae (33%) and Streptococcus pneumoniae (22%). All 361 patients were evaluable for safety. Adverse clinical events were reported in 13% (24) of cefprozil-treated patients and 20% (36) of amoxycillin/clavulanate-treated patients. Cefprozil, administered twice a day, is comparable to a regimen of amoxycillin/clavulanate three times a day in the treatment of acute otitis media in children.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Cefprozil; Cephalosporins; Child, Preschool; Clavulanic Acids; Drug Therapy, Combination; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Moraxella catarrhalis; Neisseriaceae Infections; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae

This prospective multicenter study was conducted to define more clearly clinical and laboratory criteria that predict a strong probability of occult bacteremia and to evaluate the effect of empiric broad spectrum antimicrobial treatment of these children. Children 3 to 36 months old with fever > or = 40 degrees C (104 degrees F) or, > or = 39.5 degrees C (103 degrees F) with white blood cells (WBC) > or = 15 x 10(9)/liter, and no focus of infection had blood cultures obtained and were randomized to treatment with oral amoxicillin/potassium clavulanate or intramuscular ceftriaxone. Sixty of 519 (11.6%) study patients had positive blood cultures: Streptococcus pneumoniae, 51; Haemophilus influenzae b, 6; Neisseria meningitidis, 2; and Group B Streptococcus, 1. Subgroups of high risk were identified as fever > or = 39.5 degrees C and WBC > or = 15 x 10(9)/liter, 55 of 331 or 16.6% positive with increasing incidence of positive culture with increasing increments of degrees of leukocytosis to WBC > or = 30 x 10(9)/liter where 9 of 21 or 42.9% were positive. Subgroups of significantly lower risk were identified as fever > or = 39.5 degrees C and WBC < 15 x 10(9)/liter, 5 of 182 or 2.7% positive and those with WBC < 10 x 10(9)/liter, 0 of 99 or 0.0% positive. Children with positive cultures who received ceftriaxone were nearly all afebrile after 24 hours whereas a significant number who received amoxicillin/potassium clavulanate remained febrile. In the 459 culture-negative children more amoxicillin/potassium clavulanate-treated children developed diarrhea and had less improvement in clinical scores after 24 hours than ceftriaxone-treated children.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Child, Preschool; Clavulanic Acids; Drug Therapy, Combination; Female; Fever; Follow-Up Studies; Haemophilus Infections; Humans; Infant; Injections, Intramuscular; Leukocytosis; Male; Meningococcal Infections; Multivariate Analysis; Pneumococcal Infections; Prospective Studies; Regression Analysis; Treatment Outcome

The efficacy and safety of a three-day regimen of azithromycin (500 mg od) and a ten-day regimen of co-amoxiclav (625 mg tid) were compared in a single-blind study in 99 patients with acute lower respiratory tract infections. Of these, 70 (71%) suffered an infective exacerbation of their chronic obstructive pulmonary disease. Nine patients had pneumonia and 19 purulent bronchitis. Treatment success, defined as cure or improvement, occurred in 43 of 48 (90%) patients in the azithromycin group, compared with 45 of 51 (88%) patients in the co-amoxiclav group. The most common isolated pathogens were Haemophilus influenzae (25 cases; MIC range of azithromycin (A) < or = 0.06-4 mg/L; for co-amoxiclav (CA) 0.25-4 mg/L; Streptococcus pneumoniae (10 cases; A: < or = 0.06- > 128; CA: < or = 0.06); and Moraxella catarrhalis (four cases; A: < or = 0.06; CA: < or = 0.06-0.25). Microbiological response rates were comparable in the two groups. In 5% of patients, serological evidence for virus or atypical pathogens was found. Thirteen (26%) patients treated with co-amoxiclav had gastrointestinal complaints (seven with diarrhoea), compared with five (10%) treated with azithromycin (P = 0.09). Additional complaints occurred in three patients treated with co-amoxiclav and in one patient treated with azithromycin. It was concluded that a three-day regimen of azithromycin was as effective, clinically and microbiologically, as a ten-day regimen of co-amoxiclav in the treatment of acute lower respiratory tract infections.

Topics: Adult; Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Azithromycin; Bronchitis; Clavulanic Acids; Drug Administration Schedule; Drug Combinations; Erythromycin; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Middle Aged; Moraxella catarrhalis; Neisseriaceae Infections; Pneumococcal Infections; Respiratory Tract Infections; Single-Blind Method; Streptococcus pneumoniae

A total of 102 children with recurrent otitis media or therapeutic failure after treatment with phenoxymethyl penicillin were entered into a double-blind study with parallel groups, comparing treatment with amoxycillin/clavulanate suspension (Spektramox) for 7 days with amoxycillin suspension (Imacillin) for 10 days. Bacterial and clinical investigations were performed. A total of 91 patients were evaluated for efficacy at the first follow-up visit (10-12 days after start of treatment). Amoxycillin/clavulanate and amoxycillin showed equally high, satisfactory treatment results, i.e. more than a 90% response. Similarly, there was no statistically significant difference between the treatment groups at the second follow-up visit (about 30 days after start of treatment). Bacteriological cultures from the nasopharynx showed equal distribution of Haemophilus influenzae, Branhamella catarrhalis and Streptococcus pneumoniae between the study groups. Elimination of the initially occurring pathogens was equal in the two study groups with the exception of B. catarrhalis which was eliminated to a significantly higher extent with amoxycillin/clavulanate. Both drugs were well tolerated. In patients with recurrent otitis media or therapeutic failure, treatment with amoxycillin/clavulanate for 7 days results in high, satisfactory clinical effects and is comparable to treatment with amoxycillin for 10 days.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Child, Preschool; Clavulanic Acids; Double-Blind Method; Drug Therapy, Combination; Female; Haemophilus Infections; Humans; Male; Moraxella catarrhalis; Otitis Media; Penicillin V; Pneumococcal Infections; Time Factors

A total of 150 children with acute otitis media were randomly allocated to treatment with amoxicillin-potassium clavulanate (Augmentin) or with cefaclor. Each drug was given in a daily dosage of approximately 40 mg/kg in three divided doses for ten days. Tympanocentesis done before treatment yielded specimens that contained pneumococcus or Haemophilus sp or both in 67% of specimens. Viridans group streptococci were isolated from 10% of specimens and Branhamella catarrhalis from 6%. Patients were scheduled for follow-up examinations at midtreatment, end of therapy, and at 30, 60, and 90 days. Of the 150 children, 130 were evaluable. Five of 60 patients (8%) treated with cefaclor were considered therapeutic failures because of persistent purulent drainage and isolation of the original pathogen or suprainfection. There were no failures among patients treated with Augmentin (P = .019). Rates of relapse, recurrent acute otitis media with effusion, and persistent middle ear effusion were comparable in the two groups of patients. Diaper rash, or loose stools, or both were significantly more common in children treated with Augmentin (34%) than in those taking cefaclor (12%), but in no case was it necessary to discontinue medication because of these mild side effects (P = .002). Cefaclor therapy was discontinued in one patient because of severe abdominal pain and vomiting. In this study, treatment with Augmentin was superior to treatment with cefaclor in the acute phase of acute otitis media with effusion, but Augmentin produced more adverse effects. The rates of persistent middle ear effusion and recurrent acute otitis media with effusion were comparable with the two regimens.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cefaclor; Cephalexin; Child; Child, Preschool; Clavulanic Acids; Drug Combinations; Female; Follow-Up Studies; Haemophilus Infections; Humans; Infant; Male; Otitis Media; Otitis Media with Effusion; Pneumococcal Infections; Random Allocation

Non-typeable Haemophilus influenzae (NTHi) has become the major cause of invasive H. influenzae diseases in the post-H. influenzae type b vaccine era. The emergence of multidrug-resistant (MDR) NTHi is a growing public health problem. Herein, we investigated the molecular basis of MDR in NTHi. The isolated NTHi were subjected to antimicrobial susceptibility testing for 12 agents. Whole genome and plasmid sequencing were conducted and analyzed to identify significant genetic variations and plasmid-encoded genes conferred antibiotic resistance.. This study clarified the molecular epidemiology of MDR in NTHi. This can benefit the monitoring of drug resistance trends in NTHi and the adequate medical management of patients with NTHi infection.

Topics: Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Anti-Bacterial Agents; Azithromycin; beta-Lactamases; Cefuroxime; Ciprofloxacin; Haemophilus Infections; Haemophilus influenzae; Humans; Levofloxacin; Microbial Sensitivity Tests; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination

Haemophilus influenzae is a human-specific pathogen responsible for respiratory tract infections, meningitis, and sepsis. The study aimed to characterize antibiotic resistance in H. influenzae strains isolated from patients with lower respiratory tract infections over 15 years in Poland. The minimum inhibitory concentrations (MICs) of clinically relevant antibiotics were determined by broth microdilution method. Screening for beta-lactam resistance was performed in all isolates following EUCAST recommendation. Finally, relevant changes in penicillin-binding protein 3 (PBP3) were detected by PCR screening. Of the 1481 isolates collected between 2005 and 2019, 12.6%, 0.2%, 17.1%, and 0.2% were resistant to ampicillin, amoxicillin/clavulanate, cefuroxime, and ceftriaxone, respectively. Among them, 74.4% (1102/1481) of isolates were categorized as BLNAS (β-lactamase negative, ampicillin-susceptible), 13.0% (192/1481) as BLNAS with modified PBP3 (mutations in ftsI gene), 2.6% (39/1481) as BLNAR (β-lactamase negative, ampicillin-resistant), and 0.2% had PBP3 modifications typical for high-BLNAR. Production of β-lactamase characterized 9.7% of isolates (8.6% BLPAR-β-lactamase-positive, ampicillin-resistant, and 1.1% BLPACR-β-lactamase-positive, amoxicillin-clavulanate resistant). Three isolates with PBP3 modifications typical for high-BLNAR proved resistant to ceftriaxone (MIC > 0.125 mg/L). Resistance to ciprofloxacin, chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole was observed in 0.1%, 0.5%, 1.6%, and 24.7% of isolates, respectively. This is the first report of Polish H. influenzae isolates resistant to third-generation cephalosporins. Polish H. influenzae isolates demonstrate similar susceptibility trends as in many other countries. The substantial proportion of β-lactam-resistant isolates and the emergence of those resistant to third-generation cephalosporins are of great concern and should be under surveillance.

Topics: Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Anti-Bacterial Agents; beta-Lactamases; Ceftriaxone; Drug Resistance, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Poland; Respiratory Tract Infections

Here, we report the frequency of capsulated ampicillin-resistant Haemophilus influenzae strains isolated from children in Tunisia, particularly capsular serotype b, by polymerase chain reaction (PCR) to determine the molecular mechanisms underlying ampicillin resistance.. We considered 22 capsulated H influenzae strains selected from a series of 91 ampicillin-resistant H influenzae strains isolated from children between 2010 and 2011 in Tunisia. The capsular serotypes of these strains were identified by slide agglutination and PCR.. By PCR, 19 (20.88%) serotype b, 1 (1.1%) serotype a, 2 (2.2%) serotypes d and f and 69 (75.82%) non-typeable strains were found among the 91 ampicillin-resistant H influenzae strains. 100% of the assumption between the consequences of antigenic examinations and PCR was found. The serotype b strains showed biotypes I, II, III, IV, VI, and VIII. The other capsulated strains showed biotypes IV and VIII. Thirteen of the serotype b strains created β-lactamase (14.28%). The 19 serotype b ampicillin-resistant H influenzae strains were subdivided into 3 bunches as indicated: The gathering of the β-lactamase positive, ampicillin-resistant where 11 strains (57.89%) were β-lactamase positive blaTEM-1 (+) and ftsI (+). The second gathering of the β-lactamase negative, ampicillin-resistant strains, where 6 isolates (31.58%) were β-lactamase negative blaTEM-1 (-) and ftsI (-), and lastly, the gathering of the β-lactamase positive, amoxicillin-clavulanate resistant where 2 isolates (10.52%) were β-lactamase positive blaTEM-1 (+) and ftsI (-).. PCR should be used in our country because it may contribute to decreasing the probability of transmission of these strains, especially those showing the two mechanisms of resistance among children in Tunisia.

Topics: Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Ampicillin Resistance; Anti-Bacterial Agents; beta-Lactamases; Child; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Antigens, Bacterial; Biofilms; Chinchilla; Cohort Studies; Ear, Middle; Female; Gastrointestinal Microbiome; Haemophilus Infections; Haemophilus influenzae; Haemophilus Vaccines; Immunization; Male; Otitis Media

Implementation of EUCAST susceptibility testing in an Australian hospital laboratory demonstrated higher rates of aminopenicillin and amoxicillin/clavulanate resistance in Haemophilus influenzae than previously recognized. This study aimed to better define the variability in the detection of β-lactam resistance based on EUCAST and CLSI disc diffusion (DD) methodology, by comparison with the recommended reference method, broth microdilution (BMD), and by concordance with genomic analysis.. A total of 100 random H. influenzae isolates were assessed for ampicillin and amoxicillin/clavulanate susceptibility by EUCAST and CLSI DD and BMD. WGS was used to analyse the ftsI gene of a subset of isolates with β-lactam resistance, other than that due to isolated β-lactamase production.. Of the 100 isolates, 32 were categorized as either β-lactamase negative, ampicillin resistant (BLNAR) (n = 18) or β-lactamase positive, amoxicillin/clavulanate resistant (BLPACR) (n = 14) by EUCAST DD. All 18 EUCAST BLNAR isolates were genotypically confirmed by WGS. Five of 18 BLNAR isolates were concordant by CLSI DD, 12 by EUCAST BMD and 4 by CLSI BMD. Nine of 14 EUCAST BLPACR isolates were confirmed by WGS; the remaining 5 were 1 mm below the EUCAST DD breakpoint. Only one isolate was detected as BLPACR by CLSI DD. Group III mutations associated with high-level ampicillin resistance were identified in 10/32 isolates.. The EUCAST DD susceptibility method is more reliable than either CLSI or BMD for the detection of genotypically defined BLNAR resistance. However, accurate categorization of amoxicillin/clavulanate resistance remains problematic. Continuous and reproducible surveillance of resistance is needed; for this to be possible, robust susceptibility methods are required.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Australia; beta-Lactamases; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests

Concerns about non-typeable Haemophilus influenzae (NTHi) in otitis media (OM) have grown after the introduction of pneumococcal conjugate vaccine (PCV). We aim to better understand the clinical role of NTHi in pediatric OM.. Middle ear fluid samples from children <18 years with OM were obtained from 2010 to 2015. For culture-positive episodes (Streptococcus pneumoniae, H. influenzae, Moraxella catarrhalis, and Streptococcus pyogenes), patients' demographic and clinical information were reviewed and analyzed.. A total of 783 episodes were included with 31.8% of isolates as positive. S. pneumoniae was recovered in 69.4%, NTHi in 24.6%, M. catarrhalis in 5.6%, and S. pyogenes in 4.0% of culture-positive episodes. The proportion of pneumococcal OM has declined since 2012 (P for trend <0.005), but NTHi OM rose simultaneously (P for trend = 0.009). Factors associated with increased risk of NTHi infection included less spontaneous otorrhea (OR 0.15, 95% CI 0.06-0.39, P < 0.001), absence of fever (OR 0.30, 95% CI 0.14-0.66, P = 0.003), concurrent sinusitis (OR 2.91, 95% CI 1.36-6.20, P = 0.006), previous ventilation tube insertion (OR 12.02, 95% CI 3.15-45.92, P < 0.001) and recurrent OM (OR 3.43, 95% CI 1.01-11.71, P = 0.049). The susceptibility of NTHi to amoxicillin/clavulanate was 82.0%.. NTHi OM has trended upward in the post-PCV era. Concurrent sinusitis, previous ventilation tube insertion, and recurrent OM were associated with NTHi OM implicated a correlation between NTHi and complex OM. In consideration of NTHi infection, we suggest amoxicillin/clavulanate as the first-line therapy for OM among Taiwanese children.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child, Preschool; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Microbial Sensitivity Tests; Moraxella catarrhalis; Otitis Media; Pneumococcal Vaccines; Prospective Studies; Recurrence; Risk Factors; Spain; Streptococcus pneumoniae; Streptococcus pyogenes; Vaccines, Conjugate

This study is a retrospectively recruited case series. We report three infants with acute conjunctivitis induced by β-lactamase-positive, ampicillin/clavulanic acid-resistant strains of Haemophilus influenzae (BLPACR). Patients with BLPACR-positive cultures were recruited from among 5,107 patients with inflammatory diseases of the ocular surface who underwent examinations, including bacterial culturing of conjunctival sac or corneal scrapings, between 2000 and 2015. Three BLPACR-positive patients were recruited, including a 10-month-old boy, a 4-month-old girl, and a 7-month-old girl. All three demonstrated BLPACR conjunctivitis. The clinical findings in these patients included fever, mucopurulent discharge, lid swelling, and conjunctival hyperemia. Samples of conjunctival swabs were obtained from all three infants, and BLPACR was isolated from all these conjunctival swabs. Antimicrobial susceptibility testing showed sensitivity to levofloxacin and resistance to ampicillin, cefaclor, and clarithromycin. We conclude that in infantile BLPACR conjunctivitis, simultaneous investigation for the determination of causative organism and antibiotic susceptibility testing are crucial aspects of the medical treatment.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactamases; Conjunctivitis, Bacterial; Drug Resistance, Multiple, Bacterial; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Levofloxacin; Male; Microbial Sensitivity Tests; Retrospective Studies; Topoisomerase II Inhibitors

To determine antibiotic susceptibility in isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2014-16 from Russia.. MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.. A total of 279 S. pneumoniae and 279 H. influenzae were collected. Overall, 67.0% of S. pneumoniae were penicillin susceptible by CLSI oral/EUCAST and 93.2% by CLSI intravenous (iv) breakpoints. All were fluoroquinolone susceptible, with amoxicillin, amoxicillin/clavulanic acid and ceftriaxone susceptibility ≥92.8% by CLSI and PK/PD breakpoints. Isolates showed lower susceptibility to cefuroxime, cefaclor, macrolides and trimethoprim/sulfamethoxazole by CLSI criteria: 85.0%, 76.7%, 68.8% and 67.7%, respectively. Generally, susceptibility was slightly lower by EUCAST criteria, except for cefaclor, for which the difference in susceptibility was much greater. Penicillin-resistant isolates had low susceptibility (≤60%) to all agents except fluoroquinolones. All 279 H. influenzae were ceftriaxone susceptible, 15.4% were β-lactamase positive and ≥97.5% were amoxicillin/clavulanic acid susceptible (CLSI, EUCAST and PK/PD breakpoints). Four isolates were fluoroquinolone non-susceptible by current EUCAST criteria. A major discrepancy was found with azithromycin susceptibility between CLSI (99.3%) and EUCAST and PK/PD (2.2%) breakpoints. Trimethoprim/sulfamethoxazole was poorly active (62.7% susceptible).. Susceptibility to penicillin (oral), macrolides and trimethoprim/sulfamethoxazole was low in S. pneumoniae from Russia. However, isolates were fully susceptible to fluoroquinolones and ≥92.8% were susceptible to amoxicillin, amoxicillin/clavulanic acid and ceftriaxone. Isolates of H. influenzae only showed reduced susceptibility to ampicillin, cefaclor, clarithromycin and trimethoprim/sulfamethoxazole. Some differences were detected between CLSI, EUCAST and PK/PD breakpoints, especially with cefaclor, cefuroxime and macrolides. These data suggest further efforts are required to harmonize international breakpoints.

Topics: Adolescent; Adult; Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Epidemiological Monitoring; Haemophilus Infections; Haemophilus influenzae; Humans; Macrolides; Microbial Sensitivity Tests; Middle Aged; Pneumococcal Infections; Respiratory Tract Infections; Russia; Streptococcus pneumoniae; Surveys and Questionnaires; Young Adult

To determine antimicrobial susceptibility in isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2014-16 from patients with community-acquired respiratory tract infections in Greece.. MICs were determined by CLSI broth microdilution and susceptibility assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.. A total of 99 S. pneumoniae and 52 H. influenzae isolates were collected. Overall, 36.4% of S. pneumoniae were penicillin susceptible by CLSI oral/EUCAST and 88.9% by CLSI intravenous (iv) breakpoints. All were fluoroquinolone susceptible with ≥94% of isolates also susceptible to amoxicillin, amoxicillin/clavulanic acid and ceftriaxone by CLSI and PK/PD breakpoints. Trimethoprim/sulfamethoxazole, cefuroxime, cefaclor and macrolides were less active, with rates of susceptibility of 83.8%, 69.7%, 50.5% and 49.5%, respectively, by CLSI. Generally susceptibility was the same or slightly lower by EUCAST, but the cefaclor difference was much greater. Among H. influenzae, 15.4% of isolates were β-lactamase positive. Susceptibility to amoxicillin/clavulanic acid, ceftriaxone, cefuroxime and the fluoroquinolones was seen in >95% of isolates by CLSI criteria. Susceptibility to azithromycin was seen in 94.2% of isolates using CLSI breakpoints, but clarithromycin susceptibility was lower (61.5%). However, susceptibility to both macrolides was seen in <5% of isolates by PK/PD and EUCAST criteria. Susceptibility to trimethoprim/sulfamethoxazole was seen in 71.2% of isolates.. Owing to the high prevalence of macrolide resistance among S. pneumoniae and the reduced activity of clarithromycin against H. influenzae, it appears that these agents are not appropriate as monotherapy for community-acquired pneumonia in Greece. Amoxicillin/clavulanic acid, on the other hand, maintained excellent in vitro activity and, as opposed to the similarly effective fluoroquinolones, is safe to use in paediatric patients.

Topics: Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Epidemiological Monitoring; Fluoroquinolones; Greece; Haemophilus Infections; Haemophilus influenzae; Humans; Macrolides; Microbial Sensitivity Tests; Middle Aged; Pneumococcal Infections; Respiratory Tract Infections; Streptococcus pneumoniae; Surveys and Questionnaires; Young Adult

Acute osteomyelitis of the clavicle accounts for less than 3% of osteomyelitis cases, with its usual location in the middle third. It may be hematogenous, due to contiguity, or secondary to catheterization of the subclavian vein or neck surgery. The diagnosis is often delayed, and clinical symptoms may simulate obstetric brachial plexus palsy in young children. We report a new case of osteomyelitis of the clavicle in a 30-day-old newborn.

Topics: Abscess; Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Catheterization, Central Venous; Cefotaxime; Clavicle; Female; Fever of Unknown Origin; Follow-Up Studies; Fosfomycin; Fractures, Spontaneous; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Infusions, Intravenous; Male; Osteomyelitis; Pregnancy; Pregnancy Complications, Infectious; Radionuclide Imaging; Sepsis; Streptococcal Infections; Ultrasonography

Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae (H. influenzae) are considered major causes of bacterial acute otitis media (AOM) worldwide, but data from Asia on primary causes of AOM are limited. This tympanocentesis-based, multi-center, cross-sectional study assessed bacterial etiology and antimicrobial susceptibility of AOM in Thailand.. Children 3 to 59 months presenting with AOM (< 72 hours of onset) who had not received prescribed antibiotics, or subjects who received prescribed antibiotics but remained symptomatic after 48-72 hours (treatment failures), were eligible. Study visits were conducted from April 2008 to August 2009. Bacteria were identified from middle ear fluid collected by tympanocentesis or spontaneous otorrhea swab sampling (< 20% of cases). S. pneumoniae and H. influenzae serotypes were determined and antimicrobial resistance was also assessed.. Of the 123 enrolled children, 112 were included in analysis and 48% of the 118 samples were positive for S. pneumoniae (23% (27/118)), H. influenzae (18% (21/118)), Moraxella catarrhalis (6% (7/118)) or Streptococcus pyogenes (3% (4/118)). The most common pneumococcal serotypes were 19F (26%) and 14 (22%). The majority of H. influenzae isolates were encapsulated (18/21), with 13 type b (Hib) representing 62% of all H. influenzae isolate or 11% of all samples (13/118), and there were only 3 non-typeable isolates. Despite high antibiotic resistance, amoxicillin/clavulanate susceptibility was high. No pneumococcal vaccine use was reported.. S. pneumoniae and H. influenzae, both frequently antibiotic resistant, were leading causes of bacterial AOM and there was an unexpectedly high burden of Hib in this population unvaccinated by any Hib conjugate vaccine. Conjugate vaccines effective against pneumococcus and H. influenzae could potentially reduce the burden of AOM in this population.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Cefotaxime; Child, Preschool; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Female; Haemophilus Infections; Haemophilus influenzae type b; Humans; Infant; Male; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae; Suction; Thailand

Urinary tract infections (UTIs) caused by Haemophilus parainfluenzae represent a very small percentage of this kind of pathology in children, and it has scarcely been described in the medical literature. According to previous studies of over 800 urine samples in children under 15 years old, a decrease of 50% (from 0.13% to 0.07%) is estimated in its occurrence over the last two decades. This can be explained by the early detection of UTIs and their early empirical treatment, because this micro-organism shows high sensitivity to antibiotics. Also, the culture media in which this bacterium grows are not included in most current protocols. Here we report a case of a UTI caused by H. parainfluenzae in a 4-year-old boy.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child, Preschool; Haemophilus Infections; Haemophilus parainfluenzae; Humans; Male; Urinary Tract Infections

Since the introduction of type b Haemophilus influenzae vaccination, noncapsulated H. influenzae has become responsible for most cases of invasive H. influenzae diseases. In our two cases of septic arthritis, we isolated strains with β-lactamase-positive amoxicillin-clavulanate resistance (BLPACR). Thus, the increasing prevalence of BLPACR should be taken into account when empirical therapy is chosen for septic arthritis.

Topics: Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Arthritis, Infectious; Bacterial Capsules; beta-Lactam Resistance; beta-Lactamases; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant

We sought to determine whether recurrent acute otitis media (rAOM) occurring within 30 days of amoxicillin/clavulanate treatment was caused by bacterial relapse or new pathogens.. Pneumococcal conjugate vaccinated children, age 6-36 months, enrolled in a prospective, longitudinal study experiencing rAOM<1 month after completing amoxicillin/clavulanate therapy were studied. AOM episodes occurred between June 2006 and November 2012. Multilocus sequence typing was used to genotype isolates.. Sixty-six children were in the study cohort; 63 otopathogens were recovered from middle ear fluid after tympanocentesis. Nontypeable Haemophilus influenzae (NTHi) accounted for 47% of initial AOMs versus 15% by Streptococcus pneumoniae (Spn), P<0.0001. NTHi accounted for 42% of rAOM versus 24% by Spn (P value=0.04). NTHi was the main otopathogen that caused true bacteriologic relapses (77%). β-lactamase-producing NTHi and penicillin nonsusceptible Spn were not more common in rAOM than initial AOM infections. Among 21 paired (initial and rAOM events) NTHi isolates genotyped, 13 (61.9%) were the same organism; 1 of 9 (11.1%) of paired Spn isolates was the same (P value=0.017). rAOM occurring within a week of stopping amoxicillin/clavulanate was a different pathogen in 21% of cases, 8-14 days later in 33%, 15-21 days in 41% and 22-30 days in 57% (P=0.04).. In amoxicillin/clavulanate-treated children, NTHi was the main otopathogen that caused true bacteriologic relapses. New pathogens causing rAOM versus persistence of the initial pathogen significantly increased week to week. Neither relapses nor new infections were caused more frequently by β-lactamase producing NTHi or penicillin nonsusceptible Spn.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child, Preschool; Cohort Studies; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Logistic Models; Male; Otitis Media; Pneumococcal Infections; Recurrence; Streptococcus pneumoniae

Haemophilus influenzae frequently colonizes the nasopharynx of children and adults, which can lead to a variety of infections. We investigated H. influenzae carriage in the nasopharynx of 360 children, in terms of (1) the prevalence of strains with decreased susceptibility, and (2) the presence of amino acid substitutions in PBP3. One hundred twenty-three strains were isolated (34.2%, 123/360), 122 of which were classified as nontypable H. influenzae (NTHi). Of these, β-lactamase-nonproducing ampicillin-susceptible strains accounted for 26.2%, β-lactamase-producing-ampicillin-resistant strains for 9.0%, β-lactamase-nonproducing ampicillin-resistant (BLNAR) strains for 40.2%, and β-lactamase-producing amoxicillin-/clavulanic acid-resistant (BLPACR) for 24.6%, respectively. Pulsed field gel electrophoresis (PFGE) patterns were so diverse that they were clustered into 41 groups. The amino acid substitutions in the transpeptidase domain (292 amino acids) of ftsI in BLNAR isolates showed that group IIb accounted for 30.6%, IIc for 8.2%, IId for 16.3%, III for 32.7%, and the others for 12.2%. Moreover, groups IIb (56.7%; 17/30) and III (23.3%; 7/30) were prevalent among BLPACR strains. They were subclassified into more diverse sequence subtypes by analysis of the entire PBP3 (610 amino acids). Groups IIb, IIc, IId, and III exhibited 13, four, six, and four sequence subtypes, respectively. Such a genetic diversity is likely indicative of significant potential for decreased antimicrobial susceptibility in nasopharyngeal-colonizing NTHi strains.

Topics: Amino Acid Substitution; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Ampicillin Resistance; Anti-Bacterial Agents; beta-Lactamases; Child, Preschool; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; Nasopharynx; Republic of Korea

plasmid pB1000 bearing bla(ROB-1) is responsible for high-level β-lactam resistance in Haemophilus influenzae as well as in Pasteurella multocida and Haemophilus parasuis isolates from Spain. Here, we explore the presence of ROB-1 in Italy and investigate the relative contribution of penicillin-binding protein 3 (PBP3) mutations and ROB-1 to the β-lactam resistance phenotype in H. influenzae.. the collection of the Italian Reference Laboratory of H. influenzae was investigated for ROB-1-positive isolates between 2004 and 2009. H. influenzae Rd KW20 was used as recipient for pB1000 electroporation and for mutagenesis of the ftsI gene encoding PBP3.. the presence of plasmid pB1000 in a non-typeable H. influenzae isolated in Italy, BB1059, is reported in this work. This strain is not genetically related to the H. influenzae clinical isolates bearing pB1000 described in Spain. The sequence of ftsI from BB1059 revealed several mutations in the predicted amino acid sequence of PBP3. To determine the relative contribution of pB1000 and PBP3 mutations to the β-lactam resistance phenotype of BB1059, H. influenzae Rd KW20 was transformed with ftsI and/or pB1000 from BB1059. β-Lactam resistance profiles revealed the additive effect of pB1000 and PBP3 mutations conferring resistance to β-lactams, including amoxicillin/clavulanic acid and third-generation cephalosporins.. intra-European spread of plasmid pB1000 among H. influenzae has been shown. The coexistence of plasmid pB1000 and mutations in PBP3 produces an additive resistance phenotype in H. influenzae.

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Electroporation; Haemophilus Infections; Haemophilus influenzae; Humans; Italy; Male; Mutation, Missense; Penicillin-Binding Proteins; Plasmids; Transformation, Bacterial

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Mutation; Penicillin-Binding Proteins; Taiwan

Acute otitis media is the most common respiratory tract infection in infancy and early childhood that is managed with antimicrobial agents. Ninety-three per cent of the cases diagnosed in Spain are treated with antibiotics, and Streptococcus pneumoniae and untypeable Haemophilus influenzae are the most frequently isolated pathogens. The aim of this work was to evaluate the usefulness of amoxicillin, amoxicillin/clavulanate and ceftriaxone for the empirical treatment of acute otitis media, looking at the pharmacokinetic variability and the antimicrobial susceptibility of paediatric strains of the two main pathogens responsible for AOM in Spain, Streptococcus pneumoniae and Haemophilus influenzae.. Free-drug plasma concentrations were simulated and the probability of target attainment at each minimum inhibitory concentration and the cumulative fraction of response (CFR) were determined. Microbiological susceptibility information was extracted from SAUCE 3 surveillance.. CFR with amoxicillin varied from 83% to 96% against S. pneumoniae and from 78% to 86% against H. influenzae. CFR was always >85% with amoxicillin/clavulanate. With the 3-day ceftriaxone regimen, the probability of achieving free concentrations above MIC at 72 hours significantly increased compared to the single dose, with which CFR ranged from 70% to 84%.. High-dose amoxicillin (at least 80 mg/kg/day) should be the first-line therapy in uncomplicated infections, whereas amoxicillin/clavulanate (40 mg/kg/day) should be the choice when additional coverage for H. influenzae is desired. Administration of 3 daily doses of ceftriaxone increases bacteriological eradication probability when compared with one-day regimen, although additional clinical evaluations are necessary to establish the best target attainment with ceftriaxone.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; beta-Lactam Resistance; Ceftriaxone; Child; Computer Simulation; Dose-Response Relationship, Drug; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Monte Carlo Method; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae

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

The aim of this study was to characterize ampicillin resistance mechanisms in clinical isolates of Haemophilus influenzae from Portugal. Association between specific patterns of amino acid substitutions in penicillin-binding protein 3 (PBP3) (with or without β-lactamase production) and β-lactam susceptibility as well as genetic relatedness among isolates were investigated.. Two-hundred and forty non-consecutive H. influenzae isolates chosen according to their different ampicillin MICs [101 β-lactamase-non-producing ampicillin-resistant (BLNAR) isolates, 80 β-lactamase-producing ampicillin-resistant (BLPAR) isolates and 59 β-lactamase-non-producing ampicillin-susceptible (BLNAS) isolates] were analysed. The β-lactamase-encoding bla(TEM-1) gene was detected by PCR. The ftsI gene encoding PBP3 was sequenced. Genetic relatedness among isolates was examined by PFGE.. Of the 240 H. influenzae isolates, 141 had mutations in the transpeptidase domain of the ftsI gene, including most BLNAR strains (94/101, 93.1%) and a high percentage of BLPAR strains (47/80, 58.8%). As previously reported, the latter have been described as β-lactamase-positive amoxicillin/clavulanic acid resistant (BLPACR). The most common amino acid substitutions were identified near the KTG motif: N526K (136/141, 96.5%), V547I (124/141, 87.9%) and N569S (121/141, 85.8%). The 141 strains were divided into 31 ftsI mutation patterns and included six groups (I, IIa, IIb, IIc, IId and III-like). BLNAR strains were genetically diverse but close genetic relationships were demonstrated among BLPACR strains.. This study shows that the non-enzymatic mechanism of resistance to β-lactams is widespread among H. influenzae isolates in Portugal. Clonal dissemination of BLPACR strains showing high resistance to ampicillin and reduced susceptibility to amoxicillin/clavulanic acid was documented.

Topics: Adolescent; Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; beta-Lactam Resistance; beta-Lactamases; Child; Cluster Analysis; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genotype; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Molecular Typing; Penicillin-Binding Proteins; Polymerase Chain Reaction; Polymorphism, Genetic; Portugal; Sequence Analysis, DNA

Topics: Abdominal Abscess; Adenocarcinoma; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Colorectal Neoplasms; Eikenella corrodens; Female; Gram-Negative Bacterial Infections; Haemophilus Infections; Hernia, Ventral; Humans; Intestinal Obstruction; Intestine, Small; Intraoperative Complications; Ofloxacin; Streptococcal Infections; Surgical Wound Infection; Tissue Adhesions

We report a 48-year-old male admitted to hospital due to a severe alcoholic pancreatitis. At four weeks of evolution of the acute episode, an abdominal CAT scan showed a fluid collection of 20 cm diameter located in the pancreatic tail and 2 small collections in the head. The patient received several antimicrobials and during the seventh week of evolution, while receiving vancomycin, presented fever. A fine needle aspiration of the cyst revealed the presence of Haemophilus parainfluenzae biotype VIII. The patient was treated with amoxicillin-clavulanic acid and a laparoscopic cysto-gastrostomy, with a good clinical response.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Haemophilus Infections; Haemophilus parainfluenzae; Humans; Male; Middle Aged; Pancreatic Pseudocyst; Tomography, X-Ray Computed

Streptococcus pneumoniae and Haemophilus influenzae are most important respiratory pathogens with increasing antimicrobial resistance among the key pathogens responsible for community-acquired respiratory tract infections and have the potential to limit the effectiveness of antibiotics available to treat these infections. In the present study, a total of 18 isolates of Streptococcus pneumoniae and 9 isolates of Haemophilus influenzae were characterised from specimens obtained from patients of acute respiratory tract infections including otitis media, tonsillitis, bronchitis, pneumonia and sinusitis. In the present study, all the Streptococcus pneumoniae isolates were sensitive to coamoxiclav and to cefixime, while they showed variable resistance to the other antibiotics screened. The degree of resistance to various antibiotics was as follows: Streptococcus pneumoniae showed resistance to cotrimoxazole (66.7%), azithromycin (55.6%), erythromycin (16.7%), chloramphenicol (16.7%), clindamycin (11.1%) and penicillin (11.1%). Haemophilus influenzae showed resistance to cefixime 100%, chloramphenicol 88.9%, penicillin 77.8%, erythromycin 77.8%, cefuroxime 77.8%, azithromycin 77.8%, and clindamycin 11.1%. The present study showed the emergence of variable resistance to penicillin, cotrimoxazole and other antibiotics.

Topics: Acute Disease; Adolescent; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child; Child, Preschool; Drug Resistance, Microbial; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Microbial Sensitivity Tests; Pneumococcal Infections; Respiratory Tract Infections; Streptococcus pneumoniae

Resistant strains of non-typeable Haemophilus influenzae (NTHi) are one of the principal causes of recurrent acute otitis media (otitis prone), rhinosinusitis, and pneumonia in young children. Beta-lactamase-nonproducing ampicillin-resistant (BLNAR) strains are particularly common in Japan, and beta-lactamase-producing amoxicillin-clavulanate resistant (BLPACR) strains are now emerging. We investigated the nasopharyngeal carriage status of these resistant strains among children attending a same day care center during a 10-year period.. From 1999 to 2008, we obtained nasopharyngeal swab specimens from young children attending a same day care center and examined the incidence of resistant strains of NTHi. Antimicrobial resistance of NTHi was identified based on PCR analysis of mutation of the penicillin binding protein (PBP) genes. Pulsed-field gel electrophoresis (PFGE) was performed to examine the clonal relationship of each resistant strain.. The prevalence of resistant strains of NTHi among the children attending this day care has significantly increased during the past 10 years and most of this day care children recently have resistant strains with PBP gene mutations in their nasopharynx. Genetically BLPACR (gBLPACR) strains have rapidly increased since 2007 and PFGE analysis demonstrated that all gBLPACR were clonally identical. This is the first report of apparent clonal dissemination of gBLPACR strains of NTHi occurring in a certain environment such as day care.. The rapidly increasing prevalence of resistant strains, in particular gBLPACR, in this day care center may predict a high incidence of these resistant bacteria from clinical isolates in the near future and potential serious medical problems worldwide.

Topics: Amoxicillin-Potassium Clavulanate Combination; beta-Lactamases; Carrier State; Child Day Care Centers; Child, Preschool; Disease Outbreaks; Drug Resistance, Bacterial; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Incidence; Infant; Japan; Male; Microbial Sensitivity Tests; Polymerase Chain Reaction; Retrospective Studies

Nineteen beta-lactamase-negative ampicillin-resistant (BLNAR) and 2 beta-lactamase-positive amoxicillin-clavulanic acid-resistant Canadian Haemophilus influenzae strains were characterized. All 21 isolates were found to have the N526K mutations in their ftsI genes, and their ampicillin MIC(50) values were 4-8 times that of beta-lactamase-negative ampicillin-susceptible strains. The difficulty in detection of BLNAR strains was discussed.

Topics: Adolescent; Aged; Aged, 80 and over; Amino Acid Substitution; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Ampicillin Resistance; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Canada; Child, Preschool; DNA, Bacterial; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Middle Aged; Mutation, Missense; Penicillin-Binding Proteins

We investigated the efficacy of 2 formulations of Augmentin on experimental pneumonia due to Haemophilus influenzae (HI) in rabbits. Two strains were used (H128 and 401285) with amoxicillin/clavulanic acid MICs of 1/0.5 mg/l and 4/2 mg/l. Pneumonia was induced in immunocompetent rabbits by inoculation of 10 log(10) CFU HI. The treatments were infused by using computer controlled pumps in order to mimic the human pharmacokinetic (PK) profile of either conventional Augmentin treatment (875/125 mg twice daily) or the sustained release formulation (SR: 2000/125 mg twice daily). After 2 d of treatment, the bacterial concentrations in the lungs were similar for both strains and both treatments: isolate H128, conventional Augmentin reduced bacterial numbers to 3.8+/-2.1 log(10) CFU/g and Augmentin SR to 3.1+/-2.4 log(10) CFU/g; isolate 401285, conventional Augmentin to 3.5+/-2. Thus, both treatments demonstrated similar efficacy against H. influenzae pneumonia in this model, even when induced by a strain with an amoxicillin/clavulanic acid MIC of 4/2 mg/l. These results support current breakpoints for conventional Augmentin against H. influenzae and suggest that Augmentin SR is at least as effective against these isolates.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Haemophilus Infections; Haemophilus influenzae; Male; Microbial Sensitivity Tests; Pneumonia, Bacterial; Rabbits

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Fluoroquinolones; Haemophilus Infections; Haemophilus influenzae; Humans; Pulmonary Disease, Chronic Obstructive; Time Factors

We recommend amoxacillin/clavulanate, cephalosporins and macrolides rather than penicillin as the first-line drug in chronic sinusitis with nasal polyps. In cases where there is no improvement of symptoms, cultures should be taken from the middle meatus, followed by appropriate selection of second-line antibiotics according to the sensitivity test results.. To investigate the causative bacteria and the antimicrobial susceptibility in patients with chronic sinusitis and nasal polyps in Korea.. The bacteriology and antimicrobial susceptibility of maxillary sinus aspirates from 81 patients were evaluated.. Aerobes were isolated from 58.0% of the cultures from the middle meatus and from 48.1% of those from the maxillary sinus. Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pneumoniae were the most prevalent aerobic pathogens. Anaerobes were isolated from 8.6% of the cultures from the middle meatus and from 18.5% of the cultures from the maxillary sinus. The predominant anaerobic organisms were Prevotella and Peptostreptococcus in adults but none of them were cultured in children. A high rate of concordance of the middle meatus and maxillary sinus was noted. Monomicrobial infection was most commonly observed. Ampicillin-resistant H. influenzae isolates were cultured in 46% of the cases. Penicillin resistance rates were 93% for Staph. aureus; 25% of Strep. pneumoniae were intermediate and 25% were resistant.

Topics: Adolescent; Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Infective Agents; Bacteria, Anaerobic; Bacterial Infections; Bacteriological Techniques; Cephalosporins; Child; Chronic Disease; Female; Haemophilus Infections; Humans; Macrolides; Male; Maxillary Sinus; Maxillary Sinusitis; Microbial Sensitivity Tests; Nasal Mucosa; Nasal Polyps; Penicillin Resistance; Pneumococcal Infections; Staphylococcal Infections; Statistics as Topic; Treatment Outcome

The growing resistance of Streptococcus pneumoniae to penicillin can be overcome by increasing the dose of the penicillin administered. This generated the recommendation that the adult dose of amoxicillin for the treatment of acute maxillary sinusitis (AMS) be increased from 1.5 g/day to 4.0 g/day. The objective of this study was to investigate whether the higher dose of amoxicillin is more effective than the previously recommended dose in eradicating S. pneumoniae from the nasopharynx of patients who present with AMS. Nasopharyngeal cultures obtained from 58 patients with AMS were studied: 30 received amoxicillin 1.5 g/day given in divided doses three times a day for 10 days (amoxicillin/clavulanic acid 4:1 formulation) and 28 were treated with amoxicillin 4.0 g/day given in divided doses twice a day for 10 days (amoxicillin/clavulanic acid 16:1 formulation). Seventy-one potentially pathogenic organisms were isolated: S. pneumoniae (27 isolates), Haemophilus influenzae non-type b (25), Moraxella catarrhalis (5), Streptococcus pyogenes (5) and Staphylococcus aureus (9). The number of S. pneumoniae isolates in the 1.5 g/day group was reduced from 14 to 9 (2 intermediately resistant and 3 highly resistant). In contrast, the number of S. pneumoniae isolates in the 4.0 g/day group was reduced from 13 to 2 (1 highly resistant) (P<0.05). No differences were noted in the eradication rate of other groups of isolates, which were all susceptible to amoxicillin/clavulanic acid. These data illustrate the superiority of 4.0 g/day amoxicillin/clavulanic acid compared with 1.5 g/day amoxicillin/clavulanic acid in the eradication of S. pneumoniae from the nasopharynx.

Topics: Acute Disease; Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacterial Infections; Dose-Response Relationship, Drug; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Maxillary Sinusitis; Middle Aged; Moraxella catarrhalis; Moraxellaceae Infections; Nasopharynx; Pneumococcal Infections; Staphylococcal Infections; Streptococcal Infections; Streptococcus pyogenes

A gerbil model of acute otitis media induced by Streptococcus pneumoniae plus Haemophilus influenzae was used to assess the efficacy of amoxicillin/clavulanic acid (A/C) (1.5/0.3, 2.5/0.5 and 10/2 mg/kg) and erythromycin (2.5, 10, 20 and 50 mg/kg) with or without acetaminophen. The amoxicillin/clavulanic acid MIC was 1/0.5 mg/l for both organisms and the erythromycin MICs were 0.12 and 4 mg/l for S. pneumoniae and H. influenzae, respectively. The organisms were inoculated directly into the middle ear (ME) and antibiotic treatment started 2 h post-inoculation and continued at 8h intervals for three doses. Acetaminophen was administered at 50 mg/kg. Samples for bacterial counting were obtained from the ME on day 2. Amoxicillin/clavulanic acid peri-MIC concentrations in ME were effective in eradicating both organisms. Despite the inflammation induced by S. pneumoniae, erythromycin did not eradicate H. influenzae at ME concentrations (2.4 mg/l for erythromycin 50 mg/kg) higher than those obtained in humans but lower than the MIC.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Disease Models, Animal; Drug Therapy, Combination; Erythromycin; Gerbillinae; Haemophilus Infections; Haemophilus influenzae; Microbial Sensitivity Tests; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae

Topics: Amoxicillin-Potassium Clavulanate Combination; Congenital Abnormalities; Dilatation, Pathologic; Disease Susceptibility; Drug Therapy, Combination; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Kidney; Pedigree; Pyelonephritis; Recurrence; Urinary Tract Infections

The roles of beta-lactamase and alterations in penicillin-binding protein in the development of amoxicillin and amoxicillin/clavulanate resistance in two beta-lactamase-positive, amoxicillin/clavulanate-resistant (BLPACR) strains of Haemophilus influenzae were investigated. Seven beta-lactamase-negative, ampicillin-resistant (BLNAR) strains were also studied for comparison of their resistance mechanisms. All strains had been recovered from patients in Japan. The TEM type beta-lactamase of the two BLPACR strains had 100% homology with the amino acid sequences of published TEM-1 beta-lactamase, showing that amoxicillin/clavulanate resistance was not associated with mutations in this beta-lactamase. However, these strains, as well as the seven BLNAR strains, had multiple mutations in ftsI, which encodes penicillin binding protein 3 (PBP3). The transformation of H. influenzae Rd strain with amplified ftsI genes from two BLPACR and two BLNAR strains enabled the selection of amoxicillin/clavulanate-resistant transformants with the same mutations as their parent strains. We concluded that amoxicillin/clavulanate resistance in the two BLPACR strains was due to changes in PBP3. The possibility of the presence of an extended spectrum beta-lactamase was excluded in the BLPACR strains studied.

Topics: Amino Acid Substitution; Amoxicillin-Potassium Clavulanate Combination; Bacterial Proteins; beta-Lactamases; Carrier Proteins; DNA, Bacterial; Drug Resistance, Bacterial; Drug Therapy, Combination; Haemophilus Infections; Haemophilus influenzae; Hexosyltransferases; Microbial Sensitivity Tests; Muramoylpentapeptide Carboxypeptidase; Mutation; Penicillin-Binding Proteins; Peptidyl Transferases; Transformation, Bacterial

This study determined the postantibiotic effect (PAE) of ABT-773 versus that of amoxicillin-clavulanate against clinical isolates of Streptococcus pneumoniae and Haemophilus influenzae. The PAEs of ABT-773 and amoxicillin-clavulanate ranged from 2.3 to 6.0 h and 0 to 2.2 h against S. pneumoniae and from 2.7 to 9.1 h and 0 to 0.8 h against H. influenzae, respectively.

Topics: Amoxicillin-Potassium Clavulanate Combination; Drug Resistance, Microbial; Drug Therapy, Combination; Erythromycin; Haemophilus Infections; Haemophilus influenzae; Humans; Ketolides; Microbial Sensitivity Tests; Pneumococcal Infections; Streptococcus pneumoniae

The efficacy of amoxicillin/clavulanate and cefuroxime was determined in a gerbil model of otitis media with a mixed Streptococcus pneumoniae plus Haemophilus influenzae middle ear (ME) infection. Results were compared with those obtained in a previous single H. influenzae model. All untreated animals inoculated with the mixed inoculum developed acute otitis media (AOM), whereas 86.7% of those inoculated with H. influenzae developed otitis media with effusion (OME). Antibiotics eradicated H. influenzae from the ME more efficiently in AOM than in OME, and this difference was highly significant (P80% of animals developed culture-negative OME.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Animals; Cefuroxime; Cephalosporins; Colony Count, Microbial; Disease Models, Animal; Drug Therapy, Combination; Female; Gerbillinae; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Otitis Media; Otitis Media with Effusion; Pneumococcal Infections; Streptococcus pneumoniae

FAILURES OF ANTIBIOTIC TREATMENT: The number of failures after treatment of acute middle ear infections with the 2 main antibiotics prescribed (amoxicillin and the combination amoxicillin-clavulanic acid) is on the rise. These failures appear to be related to increased resistance of the 2 principal pathogens, pneumococci and Hemophilus influenzae. A NEW FORMULATION: In order to reduce the rate of failure, it has been necessary to both increase the dose of penicillin to overcome the reduced susceptibility of pneumococci to penicillin and to prescribe a beta-lactam because of the frequent isolation of beta-lactamase producing Hemophilus influenzae. A new formulation has been developed where the amoxicillin-clavulanic acid dose is 14 to 1. This allows a daily dose of 80 mg/kg for amoxicillin and 6.4 mg/kg for clavulanic acid. In one open multicentric study including 51 pediatric patients aged 3 to 48 months with acute middle ear infections, it was demonstrated that this new formulation can be very effective in eradicating the causal agents of acute middle ear infections, including pneumococci and penicillin-resistant Hemophilus. RECOMMENDATIONS FOR GOOD EFFICACY: Amoxicillin must always be prescribed, either alone or in combination with clavulanic acid, at the dose of 45 to 50 mg/kg b.i.d. the amoxicillin-clavulanic acid combination should be preferred for children under 2 years due to the risk of beta-lactamase producing Hemophilus.

Topics: Amoxicillin-Potassium Clavulanate Combination; Chemistry, Pharmaceutical; Drug Therapy, Combination; Haemophilus Infections; Haemophilus influenzae; Humans; Otitis Media; Penicillin Resistance; Streptococcus pneumoniae

A gerbil model of otitis media induced by a beta-lactamase producing and non-serotypeable isolate of Haemophilus influenzae was used to assess the in-vivo efficacy of co-amoxiclav and cefuroxime at low (5 mg/kg) and high (20 mg/kg) doses. The MIC of the antibiotics tested against the pathogen was 1 mg/L (1/0.5 mg/L for co-amoxiclav). The organism was inoculated (+/-10(6) cfu) by transbullar challenge directly in the middle ear and antibiotic treatment was commenced 2 h post-inoculation and continued at 8 h intervals for three doses. Only high dose co-amoxiclav significantly reduced the number of culture-positive specimens as compared with untreated animals or with other treatment groups (91.7% as compared with 36.7% for high dose cefuroxime). The results obtained in any treatment group were related to middle ear antibiotic level/MIC. Antibiotic concentrations in the middle ear 90 min after administration were about 10% of serum levels at 15 min, probably related to a slight inflammatory response. Only after high dose co-amoxiclav did the concentration in the middle ear exceed the MIC by a factor of four. In otitis media with effusion, if indicated, antibiotics active in vitro should be administered in high doses and, to avoid side effects, probably in short courses.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; beta-Lactamases; Cefuroxime; Cephalosporins; Disease Models, Animal; Drug Therapy, Combination; Female; Gerbillinae; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Otitis Media with Effusion; Treatment Outcome

Susceptibility of 206 H. influenzae isolates was evaluated by disk diffusion method for 11 antimicrobial agents. No isolates were found to be resistant to third-generation cephalosporins, amoxicillin+clavulanic acid, gentamicin and ciprofloxacin. Four untypable isolates (1.9%) were beta-lactamase producing ampicillin-resistant; one of these was also resistant to chloramphenicol. The rate of resistance against rifampin was 0.5 percent.

Topics: Adolescent; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Ampicillin Resistance; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Cephalosporin Resistance; Cephalosporins; Child; Child, Preschool; Chloramphenicol; Chloramphenicol Resistance; Ciprofloxacin; Clavulanic Acids; Drug Resistance, Microbial; Drug Therapy, Combination; Gentamicins; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Italy; Serotyping

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Cefotaxime; Cellulitis; Clavulanic Acids; Conjunctivitis, Acute Hemorrhagic; Conjunctivitis, Bacterial; Drug Therapy, Combination; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male

Twenty patients, all admitted to hospital with acute purulent exacerbations of chronic bronchitis associated with Haemophilus influenzae, Streptococcus pneumoniae or beta-lactamase producing Branhamella catarrhalis were treated twice daily for ten days with amoxycillin/clavulanate. Ten patients were first given 1000 mg amoxycillin with 200 mg potassium clavulanate intravenously bd for three days, before crossing to the standard oral regimen of 1000 mg amoxycillin + 250 mg potassium clavulanate bd. Clinical results on day 10 were excellent in 16/20 patients, but 14 patients developed recurrences or reinfections within a week of the end-of-treatment, five of them with beta-lactamase producing B. catarrhalis. Bacteriological and kinetic studies showed that the branhamella beta-lactamases were inhibited by 0.25 mg/l clavulanic acid and that the mean sputum concentration of clavulanic acid was 0.16 mg/l, that of amoxycillin being 0.92 mg/l. The importance of the follow-up of such infections is stressed.

Topics: Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Bacterial Infections; beta-Lactamase Inhibitors; Bronchitis; Chronic Disease; Clavulanic Acids; Drug Combinations; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Kinetics; Male; Middle Aged; Moraxella; Recurrence; Sputum; Streptococcal Infections; Streptococcus pneumoniae

Topics: Adolescent; Adult; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactamases; Child; Clavulanic Acids; Cystic Fibrosis; Drug Combinations; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Sputum