amoxicillin-potassium-clavulanate-combination and Pneumococcal-Infections

Children attending day care centers (DCCs) frequently carry antibacterial-resistant organisms in their nasopharynx, leading to acute otitis media (AOM) that may be refractory to antibacterial treatment. The development and spread of resistant organisms are facilitated in DCCs as a result of the following: (i) large numbers of children; (ii) frequent close person-to-person contact; and (iii) a wide use of antimicrobial medications. Intensive antimicrobial usage provides the selection pressure that favors the emergence of resistant organisms, while DCCs provide an ideal environment for transmission of these organisms. The American Academy of Pediatrics and American Academy of Family Physicians' guidelines recommend high-dose amoxicillin/clavulanic acid (rather than amoxicillin alone) as the first therapeutic choice in the treatment of AOM in children attending DCCs. The introduction of the 7-valent pneumococcal conjugated vaccine (PCV7) had a major role in decreasing the number of episodes of Streptococccus pneumoniae AOM secondary to the serotypes included in the vaccine. It also had a major role in reducing the nasopharyngeal carriage of vaccine-type S. pneumoniae (and in particular of antibacterial-resistant organisms), preventing, in this way, its spread to contacts in the community. However, the recent observation of increased rates of antibacterial-resistant non-vaccine serotype S. pneumoniae may erode the success of PCV7.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child; Child Day Care Centers; Child, Preschool; Drug Resistance, Bacterial; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Infant; Infant, Newborn; Meningococcal Vaccines; Otitis Media; Pharynx; Pneumococcal Infections; Pneumococcal Vaccines; Practice Guidelines as Topic; Streptococcus pneumoniae

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

The time the free drug serum concentration of antibiotic remains above the pathogen MIC (T > MIC) determines bacteriological efficacy and emergence or selection of resistance for penicillin and amoxicillin with or without clavulanate. Multiple studies in animal and in-vitro models now support this conclusion. The size of the T > MIC (the pharmacokinetic/-dynamic target) is > 40-50% to maximise antibacterial effect and pathogen eradication for Streptococcus pneumoniae and probably also Haemophilus influenzae. The size of the T > MIC for optimal antibacterial effect is changed by host immune status but not by bacterial inoculum or mechanism of resistance. There is good animal evidence to support the prediction that, as long as the target T > MIC is achieved, strains of S. pneumoniae with amoxicillin MICs of 0.016 mg/L will respond to amoxicillin in the same way as those with MICs of 1-2 mg/L. Emergence of resistance to amoxicillin/clavulanate in S. pneumoniae is related to low T > MIC (< 20%) and also to the degree of population heterogeneity to amoxicillin. Selection of resistant strains of S. pneumoniae is also related to T > MIC. Monte Carlo simulations based on the pharmacokinetics of amoxicillin with or without clavulanate in humans are needed to best predict the likely efficacy of different amoxicillin dosing regimens. This approach adequately allows the considerable pharmacokinetic variability in amoxicillin handling by infected patients to be accounted for as well as differences in pathogen beta-lactam susceptibility.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Mice; Microbial Sensitivity Tests; Pneumococcal Infections; Rats; Streptococcus pneumoniae; Time Factors

The pharmacokinetic (PK) and pharmacodynamic (PD) profile of an antimicrobial agent provides important information that can be used to maximize bacteriologic and clinical efficacy, minimize selective pressure for the development of antimicrobial resistance, and determine an optimal dosing regimen. Judicious selection of an antimicrobial based on local susceptibility data and PK and PD parameters is imperative in this era of increasing resistance among Streptococcus pneumoniae, a leading cause of community-acquired respiratory tract infections. The beta-lactam antimicrobials display time-dependent bacterial killing with minimal to no persistent effects. Ketolides and fluoroquinolones display concentration-dependent bacterial killing, and tetracyclines and macrolides display time-dependent killing. All have prolonged persistent effects (e.g., postantibiotic effect) that retard or prevent bacterial regrowth when free drug levels fall below the minimum inhibitory concentration (MIC). New high-dose and/or extended-release formulations of traditional antimicrobials have been added to the current armamentarium for treatment of community-acquired respiratory tract infections. These formulations include amoxicillin-clavulanate potassium powder for oral suspension 90/6.4 mg/kg per day divided every 12 hours (Augmentin ES-600; GlaxoSmithKline, Research Triangle Park, NC), amoxicillin-clavulanate potassium extended-release tablets 2 x 1,000 mg/62.5 mg every 12 hours (Augmentin XR; GlaxoSmithKline), clarithromycin extended-release tablets 2 x 500 mg once daily (Biaxin XL; Abbott Laboratories, North Chicago, IL), and cefaclor extended-release tablets 375 mg or 500 mg every 12 hours (Ceclor CD; Eli Lilly Pharmaceuticals, Indianapolis, IN). Of these agents, only amoxicillin-clavulanate potassium powder for oral suspension and amoxicillin-clavulanate potassium extended-release tablets were designed to treat infections caused by penicillin-resistant pneumococci (penicillin MIC < or =2 microg/mL). Extended-release clarithromycin does not provide higher daily doses than its immediate-release counterpart; rather, it allows for once-daily dosing of this agent because of its slower absorption following oral administration. Extended-release cefaclor is considered clinically equivalent to 250 mg of immediate-release cefaclor pulvules administered 3 times daily; it cannot be used interchangeably with 500 mg 3-times-daily dosages of other cefaclor formulations. Thus, despite provid

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Delayed-Action Preparations; Humans; Pneumococcal Infections; Powders; Respiratory Tract Infections; Streptococcus pneumoniae

Acute bacterial rhinosinusitis (ABRS) is a secondary bacterial infection of the nose and paranasal sinuses, usually preceded by a viral upper respiratory infection or allergy, with symptoms that have not improved after 10 days or that have worsened after 5 to 7 days. Streptococcus pneumoniae and Haemophilus influenzae are the most common causes of ABRS in adults. Increasing rates of antimicrobial resistance among S. pneumoniae and beta-lactamase production among H. influenzae are formidable challenges to the successful treatment of infections caused by these organisms. To this end, various formulations of amoxicillin-clavulanate have been developed, the most recent of which is pharmacokinetically enhanced and provides a total daily dose of 4,000 mg of amoxicillin and 250 mg of clavulanate. This formulation has been shown to be safe and effective in the treatment of infections caused by penicillin-resistant S. pneumoniae (minimum inhibitory concentration 2 microg/mL); the clavulanate component provides adequate coverage of beta-lactamase-producing pathogens.

Topics: Acute Disease; Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Therapy, Combination; Haemophilus influenzae; Humans; Penicillin Resistance; Pneumococcal Infections; Rhinitis; Sinusitis; Streptococcus pneumoniae

Genital tract infections in females secondary to Streptococcus pneumoniae (pneumococcus) are unusual. Tubo-ovarian abscess resulting from such an infection is a rare occurrence and diagnosis is not always easy. This report demonstrates the problems of recognizing this condition and summarizes the pathomechanism, investigations leading to a diagnosis and the subsequent management.. A rare case of a tubo-ovarian abscess caused by pneumococcus, occurring in a previously healthy 48-year-old woman, is presented. The tubo-ovarian abscess may have developed insidiously and probably had an acute exacerbation prior to presentation.. This case is unusual in that there were no identifiable initiating events for the source of the pneumococcal infection. Early recognition of a tubo-ovarian abscess is important in order to prevent the associated morbidity and mortality. This condition has the propensity to mimic a neoplasm.

Topics: Abscess; Amoxicillin-Potassium Clavulanate Combination; Climacteric; Diagnosis, Differential; Drug Therapy, Combination; Fallopian Tube Diseases; Female; Humans; Laparotomy; Middle Aged; Ovarian Diseases; Pneumococcal Infections; Streptococcus pneumoniae

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

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

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

Antibiotic-resistant pneumococci are difficult to eradicate from middle ear fluid (MEF) and the nasopharynx (NP). Bacteriologic eradication from the NP and MEF during acute otitis media (AOM) by 3 common antibiotic drugs was prospectively evaluated. In 19 (16%) of 119 MEF culture-positive patients, an organism susceptible to the treatment drug (Haemophilus influenzae, Streptococcus pneumoniae, or both) was isolated from the initial MEF, whereas resistant S. pneumoniae was present in the NP; in 9 (47%) patients, the initial resistant NP organism (identified by serotyping, resistance to the administered drug, and pulsed-field gel electrophoresis) replaced the susceptible MEF organism within only a few days after initiation of treatment. In regions where resistant pneumococci are prevalent, antibiotics may not only fail to eradicate the organisms, but they may often induce MEF superinfection with resistant pneumococci initially carried in the NP. This is an important mechanism by which, in recently treated patients, AOM infections often become refractory to treatment.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child; Drug Resistance, Microbial; Drug Therapy, Combination; Ear, Middle; Female; Humans; Male; Nasopharynx; Otitis Media; Pneumococcal Infections; Serotyping; Streptococcus pneumoniae; Superinfection; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

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

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Child; Child, Preschool; Diarrhea; Double-Blind Method; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Gastroenteritis; Humans; Infant; Male; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae

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

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

To compare dispensed oral antibiotic prescription rates (DAPRs) after implementation of pneumococcal conjugate vaccine (PCV) in high antibiotic-prescribing clinics (HPC) with low antibiotic-prescribing clinics (LPC) in 2 distinct ethnic groups of children (Jewish and Bedouin children) <5 years of age.. Clinics with ≥50 insured children, active both pre-PCV (2005-2009) and post-PCV (2010-2018) implementation, were included. HPC and LPC were defined by DAPRs above or below the median in each age and ethnic group. Monthly dispensed antibiotic prescription rate (DAPR) trends (adjusted for age and ethnicity) were calculated using interrupted time series. Mean yearly incidence rate-ratios (late PCV13 vs pre-PCV) were calculated.. Bedouin HPC had the highest pre-PCV overall-DAPR per 1000 child-years ± SD (2520.4 ± 121.2), followed by Jewish HPC (1885.5 ± 47.6), Bedouin LPC (1314.8 ± 81.6), and Jewish LPC (996.0 ± 19.6). Shortly after PCV implementation, all DAPRs and amoxicillin/amoxicillin-clavulanate DAPRs declined in all groups except Jewish LPC, stabilizing within 4-5 years post-PCV. The rates and magnitudes of declines were directly proportional to the pre-PCV DAPR magnitudes, achieving near-complete closure of the pre-PCV DAPR gaps between the 4 groups (rates during late-PCV13 ranging from 1649.4 ± 23.5 [Bedouin HPC] to 1200.3 ± 72.4 [Jewish LPC]).. PCVs are a powerful tool in reducing outpatient antibiotic consumption among young children, especially in HPC, resulting in partial closure of DAPR gap between HPC and LPC. The higher impact on HPC suggests that PCV-associated declines of respiratory disease may strongly contribute to a judicious antibiotic approach in clinics with high antibiotic consumption.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child; Child, Preschool; Humans; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccines, Conjugate

The aim of the study was to evaluate the activity of Raphamin in a model of non-lethal pneumococcal infection caused by Streptococcus pneumoniae 3 in BALB/c mice. The drug or placebo was administered intragastrically 3 days prior to infection, 2 h before and 2 h post infection, and then for 3 full days, alone or in combination with antibiotic (amoxicil-lin/clavulanic acid). Raphamin monotherapy significantly decreased bacterial load in the lungs in comparison with placebo (p<0.05) which was comparable to the effect in antibiotic alone or combined with Raphamin. Raphamin prevented reproduction of Streptococcus pneumoniae in the lower respiratory tract and its combination with the antibiotic was safe and did not reduce the efficacy of amoxicillin/clavulanic acid.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Clavulanic Acid; Mice; Pneumococcal Infections; Streptococcus pneumoniae

Data related to carriage of Streptococcus pneumoniae (Spn) and antimicrobial resistance patterns in middle-aged and older adults are limited. We assessed the carriage of Spn, and its antibiotic resistance patterns, among participants ≥50 years of age living in the city of Novi Sad during the second year of COVID-19 pandemic.. Analysis of prospectively collected data among participants with or without symptoms of upper respiratory tract infection who visited their elected physicians in the Primary Health Care Centre of Novi Sad (outpatient facility) was conducted from May 18, 2021 to December 7, 2021. Both nasopharyngeal (NP) and oropharyngeal (OP) samples from each participant were collected.. A total of 1042 samples from 521 study subjects (1 NP and 1 OP sample from each person) were collected. Sixteen samples from the same number of persons (3.1%, 95% confidence interval: 1.76%-4.94%) were culture positive for the presence of Spn. Overall, the median age of study participants was 71 years (range, 50-93 years; 90th percentile, 77 years), and most (197/521, 37.8%) of them were 70-79 years of age. A majority of the study subjects were: females (324/521; 62.2%), sampled during May and June 2021 (376/521, 72.2%), those who did not have contact with children aged 0-10 years in the family (403/521; 77.4%), without smokers in the household (443/521; 85.0%), and those who did not receive vaccine against Spn (519/521; 99.6%). Out of 16 Spn positive samples, for six participants, Spn carriage serotypes were obtained and there were four vaccine (6A, 11A, 15B, and 18C) serotypes, and two (6C and 35F) non-vaccine serotypes. Remaining 10 (62.50%) samples were non-typeable isolates of pneumococci. Among four vaccine serotypes, two (6A and 18C) were represented in PCV13, and 18C along with the other two (11A and 15B) in PPSV23 vaccine. The highest level of resistance of Spn isolates was observed for erythromycin, (10 or 62.50%), and tetracycline, (7 or 43.75%), one isolate showed resistance to penicillin, ampicillin, and amoxicillin/amoxicillin-clavulanic acid, while none of them were resistant to ceftriaxone, trimethoprim/sulfamethoxazole and levofloxacin. There were three multi-drug resistant isolates; one was identified as 6C (non-vaccine serotype), and two other were non-typeable isolates of Spn.. In this first study conducted in Serbia on Spn carriage in adults ≥50 years of age, we found low prevalence of Spn carriage and identified 6 serotypes of Spn, four of which were represented in vaccines. These results may support future Spn colonization studies among middle-aged and older adults.

Topics: Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Carrier State; Ceftriaxone; Child; COVID-19; Delivery of Health Care; Erythromycin; Female; Humans; Infant; Levofloxacin; Middle Aged; Nasopharynx; Outpatients; Pandemics; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Serbia; Serogroup; Streptococcus pneumoniae; Tetracyclines; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumococcal conjugate vaccines (PCVs) reduce respiratory infections in young children, the main antibiotic consumers. Following PCV implementation, dispensed antibiotic prescription (DAP) rates in young children were expected to decline.. Computerized data on DAP for children <5 years were examined during a 13-year period (including 4 pre-PCV years). All DAPs from clinics with ≥50 insured children, active both pre- and post-PCV implementation were included. Interrupted time-series with segmented regression was applied to analyze monthly DAP rate trends, adjusted for age, ethnicity, and season. Incidence rate ratios (IRRs) of DAPs during the late PCV13 period versus 4 years pre-PCV were calculated both as absolute rate ratios (aIRRs) and relative to expected rates (rIRRs).. Of 1 090 870 DAPs, 57% were in children <2 years. All-DAP rates peaked in the cold season. Post-PCV7/PCV13 implementation, all DAP rates abruptly and significantly declined, reaching a plateau within 5 years. This was largely driven by amoxicillin/amoxicillin-clavulanate (75% of DAPs). Age <2 years and Bedouin ethnicity were significantly associated with higher pre-PCV DAP rates but with faster and greater decline post-PCV, achieving near elimination of gaps between ages and ethnic groups. Overall reduction (95% CIs) in DAP rates per 1000 was estimated between aIRR (344.7 [370.9-358.4]) and rIRR (110.4 [96.9-123.7]) values.. Shortly following PCV implementation, overall DAP rates showed an abrupt, steep decline, stabilizing within 5 years, in parallel to post-PCV respiratory infection trends previously described in this population, suggesting causality. The variable patterns of certain drug categories suggest additional influences beyond PCV.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Arabs; Child; Child, Preschool; Humans; Incidence; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Vaccines, Conjugate

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

Streptococcus pneumoniaeis one of the key pathogens responsible for otitis media (OM), the most common infection in children and the largest cause of childhood antibiotic prescription. Novel therapeutic strategies that reduce the overall antibiotic consumption due to OM are required because, although widespread pneumococcal conjugate immunization has controlled invasive pneumococcal disease, overall OM incidence has not decreased. Biofilm formation represents an important phenotype contributing to the antibiotic tolerance and persistence ofS. pneumoniaein chronic or recurrent OM. We investigated the treatment of pneumococcal biofilms with nitric oxide (NO), an endogenous signaling molecule and therapeutic agent that has been demonstrated to trigger biofilm dispersal in other bacterial species. We hypothesized that addition of low concentrations of NO to pneumococcal biofilms would improve antibiotic efficacy and that higher concentrations exert direct antibacterial effects. Unlike in many other bacterial species, low concentrations of NO did not result inS. pneumoniaebiofilm dispersal. Instead, treatment of bothin vitrobiofilms andex vivoadenoid tissue samples (a reservoir forS. pneumoniaebiofilms) with low concentrations of NO enhanced pneumococcal killing when combined with amoxicillin-clavulanic acid, an antibiotic commonly used to treat chronic OM. Quantitative proteomic analysis using iTRAQ (isobaric tag for relative and absolute quantitation) identified 13 proteins that were differentially expressed following low-concentration NO treatment, 85% of which function in metabolism or translation. Treatment with low-concentration NO, therefore, appears to modulate pneumococcal metabolism and may represent a novel therapeutic approach to reduce antibiotic tolerance in pneumococcal biofilms.

Topics: Adenoids; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Biofilms; Child; Child, Preschool; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Gene Expression Regulation, Bacterial; Humans; Hydrazines; Nitrates; Nitric Oxide; Nitric Oxide Donors; Nitroprusside; Otitis Media; Pneumococcal Infections; Protein Biosynthesis; Sodium Nitrite; Streptococcus pneumoniae; Transcription, Genetic

We aimed to identify the causative organisms and sensitivities in community-acquired paediatric empyema at Starship Children's Hospital and Christchurch Hospital and to determine if current antibiotic recommendations are appropriate.. Retrospective analysis was undertaken of all cases with clinical, radiological, and microbiological evidence of empyema at Starship Children's Hospital and Christchurch Hospital between June 2009 and March 2013 (3.8 years), and January 2009 and May 2014 (5.4 years) respectively.. Ninety-eight children were managed with empyema at Starship Children's Hospital and 30 children at Christchurch Hospital. Staphylococcus aureus was the most common pathogen identified at both sites followed by Streptococcus pneumoniae. A significant proportion had no pathogen identified. Amongst S.aureus isolates, 1/5th were methicillin-resistant, contributing 8% of all culture positive empyema cases. Māori and Pacific groups were over-represented. Cases occurred more often in boys and those <5 years. Blood cultures and S.pneumoniae pleural antigen were important in diagnosis.. Our audit confirms the important role of S.aureus in paediatric empyema in New Zealand and a high rate of this disease, particularly in the North Island. Antimicrobial susceptibilities of the pathogens of empyema demonstrate current initial antibiotic recommendation.

Topics: Adolescent; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cefotaxime; Cefuroxime; Child; Child, Preschool; Cohort Studies; Community-Acquired Infections; Empyema, Pleural; Ethnicity; Female; Floxacillin; Hospitals, Pediatric; Hospitals, Urban; Humans; Infant; Infant, Newborn; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; New Zealand; Pneumococcal Infections; Practice Guidelines as Topic; Retrospective Studies; Seasons; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus pneumoniae; Streptococcus pyogenes

In the last decade, the Streptococcus pneumoniae population has changed, mainly due to the abuse of antibiotics. The aim of this study was to determine the genetic structure of 144 S. pneumonia serotype 14 isolates collected from children with acute respiratory infections during 1997-2012 in China.. All isolated pneumococci were tested for their sensitivity to 11 kinds of antibiotics with the E-test method or disc diffusion. The macrolides resistance genes ermB and mefA, as well as the sulfamethoxazole-trimethoprim resistance gene dihydrofolate reductase (DHFR) were detected by polymerase chain reaction (PCR). The sequence types (STs) were analyzed with multilocus sequence typing (MLST).. From 1997 to 2012, the percentage of serotype 14 S. pneumonia isolates in the whole isolates increased. All of the 144 serotype 14 S. pneumonia isolates were susceptible to amoxicillin-clavulanic acid, vancomycin and levofloxacin. No penicillin resistant isolate was found, and the intermediate rate was as low as 0.7 %. Erythromycin resistance was confirmed among 143 isolates. The ermB gene was determined in all erythromycin resistant isolates, and the mefA gene was positive additionally in 13 of them. The non-susceptibility rate to the tested cephalosporins increased from 1997-2012. All trimethoprim-resistant isolates contained the Ile100-Leu mutation. Overall, 30 STs were identified, among which ST876 was the most prevalent, followed by ST875. During the study period, the percentage of CC876 increased from 0 % in 1997-2000 to 96.4 % in 2010-2012, whereas CC875 decreased from 84.2 to 0 %. CC876 showed higher non-susceptibility rates to β-lactam antibiotics than CC875.. The percentage of serotype 14 S. pneumonia isolates increased over time in China. The increase of resistance to β-lactam antibiotics in this serotype isolates was associated with the spread of CC876.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child, Preschool; China; Drug Resistance, Bacterial; Erythromycin; Humans; Infant; Infant, Newborn; Multilocus Sequence Typing; Pneumococcal Infections; Polymerase Chain Reaction; Respiratory Tract Infections; Serogroup; Streptococcus pneumoniae

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

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

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

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

Topics: Abscess; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cellulitis; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pneumococcal Infections; Streptococcus pneumoniae

Pneumococcal diseases remain a major cause of morbidity and mortality worldwide. Updated data on drug-resistance from different populations may be important to recognize changes in disease patterns. This study assessed current levels of penicillin resistance among Streptococcus Pneumoniae causing pneumonia in Spanish middle age and older adults.. Antimicrobial susceptibility was tested for 104 consecutive isolates of Streptococcus pneumoniae recovered from patients 50 years or older with radiographically confirmed pneumonia in the region of Tarragona (Spain) between 2002 and 2007. According to the minimum inhibitory concentration of tested antimicrobials (penicillin, erythromycin, cefotaxime and levofloxacin) strains were classified as susceptible or resistant. Antimicrobial resistance was determined for early cases (2002-2004) and contemporary cases (2005-2007).. Twenty-seven (25.9%) were penicillin-resistant strains (19 strains with intermediate resistance and 8 strains with high resistance). Penicillin-resistance was higher in 2002-2004 than in 2005-2007 (39.5% vs 18.2%, p = 0.017).Of 27 penicillin-resistant strains, 10 (37%) were resistant to erythromycin, 8 (29.6%) to cefotaxime, 2 (7.4%) to levofloxacin, and 4 (14.8%) were identified as multidrug resistant. Case-fatality rate was higher among those patients who had an infection caused by any penicillin susceptible strain (16.9%) than in those with infections due to penicillin-resistant strains.. Resistance to penicillin among Streptococcus pneumoniae remains high, but such resistance does not result in increased mortality in patients with pneumococcal pneumonia.

Topics: Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Blood; Cefotaxime; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Erythromycin; Female; Humans; Levofloxacin; Male; Middle Aged; Ofloxacin; Oxacillin; Pneumococcal Infections; Serotyping; Spain; Sputum; Streptococcus pneumoniae

The empiric choice of initial antibiotherapy in osteoarticular infections in infants and children must take into consideration the actual epidemiology of principal pathogens, their respective antibiotic sensitivity profile, their pharmacokinetic and pharmacodynamic properties and the results of efficacy clinical studies. After a review of recent data concerning these four major points, the Paediatric Infectious Diseases Group of the French Society of Paediatrics (GPIP) has proposed guidelines for initial recommended schemes of antimicrobial therapy in acute and non complicated osteoarticular infections in infants and children.

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bone Diseases, Infectious; Child; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Infant; Joint Diseases; Kingella kingae; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Neisseriaceae Infections; Penicillins; Pneumococcal Infections; Pristinamycin; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

We report Hemolytic Uremic Syndrome (HUS) induced by Streptococcus pneumoniae in a 20 month-old girl. She responded well to hemodialysis.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Female; Hemolytic-Uremic Syndrome; Humans; Infant; Pneumococcal Infections; Risk Factors; Streptococcus pneumoniae

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cefotaxime; Child; Child, Preschool; Drug Resistance, Bacterial; Erythromycin; Humans; Infant; Microbial Sensitivity Tests; Penicillin G; Pneumococcal Infections; Serotyping; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination; Turkey

We report the case of a 5-month-old female infant who developed a progressive unilateral retroauricular swelling without further symptoms in the first 5 months of life. The otherwise healthy infant was breast fed and had no history of previous otitis media. The clinical suspicion of silent mastoiditis was confirmed by CT scans and the intraoperative finding of an abscess due to Streptococcus pneumoniae. The onset is unusual, since mastoid pneumatization develops only after birth, and it is presumed that maternal antibodies should protect the infant from serious infections within the first months of life.

Topics: Abscess; Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Combined Modality Therapy; Diagnosis, Differential; Drainage; Female; Humans; Infant; Infusions, Intravenous; Mastoid; Mastoiditis; Pneumococcal Infections; Tomography, X-Ray Computed

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

Topics: Adolescent; Adult; Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Female; Humans; Male; Middle Aged; Pneumococcal Infections; Sinusitis; Treatment Outcome

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 Streptococcus pneumoniae (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).. 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 Streptococcus pneumoniae.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child; Child, Preschool; Epidemiologic Methods; Female; Humans; Infant; Male; Nasopharynx; Otitis Media; Pneumococcal Infections; Sex Factors; Treatment Outcome

A contemporary (2002-2003) national collection of 2100 strains of Streptococcus pneumoniae obtained from 30 sites in the nine United States (US) census regions were tested to determine the comparative antimicrobial properties of amoxicillin/clavulanate and 15 other antimicrobials. The rank order of antimicrobials with the lowest susceptibility rates was: penicillin (67.9%)or=41.1%), trimethoprim/sulphamethoxazole (38.9%), tetracyclines (22.2%) and clindamycin (10.0%). Geographical variation in the susceptibility patterns among US census zones was present with lowest penicillin and erythromycin susceptibility noted for West South Central and West North Central zones (or=+0.9%), sinus isolates (+2.7%), middle ear fluid isolates (+5.5%), penicillin-resistant strains (>or=+5.8%) and strains from patients <2 years of age (>or=+2.4%). Local and global surveillance studies of common respiratory pathogens such as S. pneumoniae remain instrumental to guide clinicians in appropriate empirical treatments and to emphasize the need for prudent antimicrobial use.

Topics: Adolescent; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child; Child, Preschool; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Infant; Microbial Sensitivity Tests; North America; Pneumococcal Infections; Respiratory Tract Infections; Streptococcus pneumoniae

Compared with European countries, the use of antibiotics in Slovenia is moderate. In the period 1999-2002 an 18.67% decrease in outpatient antibiotic consumption was noted. The aim of the present study was to analyse this decrease and its consequences.. The data on outpatient antibiotic consumption were obtained from the Institute of Public Health and Health Insurance Institute of Slovenia and expressed in defined daily doses (DDD)/1000 inhabitant-days. The number of media publications on 'antibiotic drugs' and 'bacterial resistance' during the study period was obtained. In 2000, the prescription of co-amoxiclav and fluoroquinolones was restricted because of a constant increase in the consumption of these drugs. The data on incidence of acute mastoiditis and penicillin resistance among invasive pneumococci were obtained.. The total outpatient consumption of antibacterials increased from 15.21 DDD/1000 inhabitant-days in 1996 to 20.08 in 1999, and decreased to 16.97 in 2003. The consumption of restricted antibiotics decreased from 7.29 in 1999 to 5.25 DDD/1000 inhabitant-days in 2003. There was a positive correlation between antibiotic consumption and the number of newspaper articles (r=0.92), and a negative correlation between the number of diagnostic tests and antibiotic consumption (r=-0.73 for the C-reactive protein test and -0.68 for the streptococcal antigen detection test). Reduced antibiotic consumption was paralleled by a decrease in penicillin resistance among invasive pneumococci. No increase in mastoiditis cases was observed in spite of reduced antibiotic consumption.. Restriction of antibiotic prescription proved to be effective in reducing outpatient antibiotic consumption. The effect was prolonged and affected restricted antibiotics as well as non-restricted drugs.

Topics: Ambulatory Care; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Utilization; Fluoroquinolones; Mastoiditis; Penicillin Resistance; Pneumococcal Infections; Retrospective Studies; Slovenia; Streptococcus pneumoniae

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

Using pharmacokinetic/pharmacodynamic principles, pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg twice daily was designed to provide adequate levels of amoxicillin over the 12-h dosing interval to eradicate penicillin-resistant Streptococcus pneumoniae (PRSP, penicillin MICs > or = 2 mg/L) with amoxicillin MICs of at least 4 mg/L. The clinical efficacy of amoxicillin/clavulanate 2000/125 mg was evaluated in patients with respiratory tract infections caused by S. pneumoniae, including isolates with elevated penicillin (2-8 mg/L) MICs. Data from 10 clinical studies were combined: seven randomised (1:1), double-blind, controlled trials (efficacy intent-to-treat [ITT]N = 3376): amoxicillin/clavulanate 2000/125 mg twice daily vs. levofloxacin 500 mg once daily in acute bacterial sinusitis (ABS); levofloxacin 500 mg once daily in acute exacerbations of chronic bronchitis (AECB); clarithromycin 500 mg twice daily in AECB; amoxicillin/clavulanate 875/125 mg twice daily/three times daily and 1000/125 mg three times daily in community-acquired pneumonia (CAP) and three noncomparative studies (efficacy ITT N = 3024): two in ABS, one in CAP. The bacteriological per-protocol (PP) population at follow up (days 14-39) comprised 1295 patients for amoxicillin/clavulanate 2000/125 mg and 241 for comparators. With amoxicillin/clavulanate 2000/125 mg at follow-up, outcome was successful (clinical success and eradication/presumed eradication) in 85/90 (94.4%) patients with S. pneumoniae in comparative studies and 421/445 (94.6%) in noncomparative studies, and with comparators 58/70 (82.9%) were successes. In the amoxicillin/clavulanate 2000/125 mg group at follow up, 52/552 S. pneumoniae isolates were resistant to penicillin. At follow up, 50/52 (96.2%) patients with PRSP were successes, including 6/7 with amoxicillin MICs of 4 mg/L and 7/8 with amoxicillin MICs of 8 mg/L. Success rates for amoxicillin/clavulanate 2000/125 mg against PRSP were similar for CAP (96.0%[24/25]), AECB (100%[3/3]) and ABS (95.8%[23/24]). There were six PRSP isolates in the comparator group (two isolates were from one patient), and three of five patients in this group were successes. In conclusion, amoxicillin/clavulanate 2000/125 mg demonstrated combined clinical/bacteriological success against 50/52 patients with PRSP, including 13/15 strains with amoxicillin MICs of 4-8 mg/L. These results for the pharmacokinetic-enhanced formulation of amoxicillin/clavulanate 2000/125 mg are in

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Double-Blind Method; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Penicillin Resistance; Pneumococcal Infections; Randomized Controlled Trials as Topic; Streptococcus pneumoniae; Treatment Outcome

BB-81384, a novel peptide deformylase (PDF) inhibitor, was characterized in terms of enzyme inhibition profile, antibacterial activity, rodent pharmacokinetics and oral efficacy in murine infection models.. MICs were determined by standard NCCLS broth microdilution. Selectivity of metalloenzyme inhibition was determined with a limited panel of enzymes via standard biochemical assays. Profiling of the pharmacokinetics and select tissue disposition in mice was determined and compared with that of the macrolide, azithromycin. In vivo murine efficacy studies using Streptococcus pneumoniae were conducted using a peritonitis model, as well as lung and thigh burden models of infection.. BB-81384 selectively inhibited PDF with an IC(50) approximately 10 nM and with MICs < 0.5 mg/L against most S. pneumoniae pathogens. Pharmacokinetic analysis revealed good oral bioavailability and moderate clearance and volume of distribution. BB-81384 partitioning to lung tissue was similar in terms of magnitude and kinetics to that of the plasma compartment. Single-administration oral efficacy in a mouse peritonitis model was evident with an ED(50) of 30 mg/kg. BB-81384 reduced the bacterial load by approximately 5 and 3 log units in organ-burden models of lung and thigh infection, respectively.. BB-81384, a novel PDF inhibitor with good activity against S. pneumoniae in vitro, was the first compound of this class to be profiled for oral pharmacokinetics and tissue disposition and to demonstrate oral anti-pneumococcal efficacy in mice.

Topics: Amidohydrolases; Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Azithromycin; Bacteria; Drug Therapy, Combination; Enzyme Inhibitors; Kinetics; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Muscle, Skeletal; Muscular Diseases; Neutropenia; Peritonitis; Piperazines; Pneumococcal Infections; Pneumonia; Streptococcus pneumoniae; Tissue Distribution

Nasopharyngeal cultures were obtained from 60 children with acute otitis media before and after treatment with either 45 or 90 mg of amoxicillin (given as amoxicillin-clavulanate) per kg of body weight per day for 10 days. The number of Streptococcus pneumoniae isolates in the 45-mg/kg group was reduced from 12 to 6 and was reduced from 14 to 1 (P = 0.0261) in the 90-mg/kg group.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Nasopharynx; Otitis Media; Penicillins; Pneumococcal Infections; Streptococcus pneumoniae

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Community-Acquired Infections; Delayed-Action Preparations; Diarrhea; Drug Therapy, Combination; Humans; Pneumococcal Infections; Randomized Controlled Trials as Topic; Sinusitis

The bactericidal activities of ABT-773, a new ketolide, were compared to those of cefuroxime and amoxicillin-clavulanate against 10 strains of Streptococcus pneumoniae containing the ermB gene. MICs and time-kill curves were determined in duplicate per NCCLS guidelines with cation-adjusted Mueller-Hinton broth with 3% lysed horse blood. Viable counts were done at 0, 2, 6, and 24 h. Antibiotic concentrations tested were two and eight times the MIC. ABT-773 MICs ranged from 0.008 to 1.0 micro g/ml. Bactericidal activity was observed with ABT-773 at eight times the MIC against 4 of 10 strains at 24 h compared to 10 of 10 strains with the beta-lactam antibiotics.

Topics: Amoxicillin-Potassium Clavulanate Combination; Cefuroxime; Cephalosporins; Culture Media; Drug Therapy, Combination; Erythromycin; Humans; Ketolides; Kinetics; Methyltransferases; Microbial Sensitivity Tests; Pneumococcal Infections; Streptococcus pneumoniae

Topics: Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Macrolides; Methyltransferases; Pneumococcal Infections; Streptococcus pneumoniae; Treatment Failure

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Ceftriaxone; Child, Preschool; Combined Modality Therapy; Drug Therapy, Combination; Erythrocyte Transfusion; Hemolytic-Uremic Syndrome; Humans; Incidence; Male; Pneumococcal Infections; Prognosis; Risk Factors; Severity of Illness Index; Treatment Outcome

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

Amoxicillin-clavulanic acid is a first choice treatment for respiratory tract infections caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In a previous study we observed its high efficacy against penicillin-susceptible and intermediate-resistant strains of S. pneumoniae. We aimed to study the efficacy of this antibiotic against three strains of S. pneumoniae (susceptible, intermediate and resistant to penicillin) in a mouse model of pneumonia, and to determine the influence of the time of starting treatment and the in vitro postantibiotic effect. We also determined the serum levels of the antimicrobial agent in the mice, and correlated the pharmacodynamic parameters (Cmax/MIC, AUC/MIC and T>MIC) with the survival rate to establish the best predictor of efficacy. MICs with amoxicillin-clavulanic acid were 0. 03 mg/l, 0.25 mg/l and 2 mg/l for the penicillin-susceptible, -intermediate and -resistant strains, respectively. The ED90 were approximately 5 mg/kg for susceptible strains, 25 mg/kg for the intermediate and 50 mg/kg for the resistant strains. We observed a lower survival rate (approximately 55%) when the treatment began 31 h after infection than when it began 5 h (100%) and 19 h (approximately 90-100%) afterwards. Serum levels were dose dependent and the correlation with the pharmacodynamic parameters showed a significant association between survival and the T>MIC (r = 0.946). In vitro postantibiotic effects with 1, 4 and 10 times the MIC were 0.96 to 1.69 h for susceptible strains, 0.38 to 1.23 h for intermediate, and 1.52 to 2. 20 h for resistant strains. These results show the high efficacy of this antibiotic combination against strains with variable susceptibility to penicillin, with this activity being related mainly to the T>MIC of the microorganism. The postantibiotic effect would prolong the effect of the antibiotic in the dosing interval. These parameters and antimicrobial effects are important in terms of the clinical application of this antimicrobial agent.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Drug Therapy, Combination; Mice; Microbial Sensitivity Tests; Pneumococcal Infections; Streptococcus pneumoniae; Survival Analysis

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

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

The purpose of the present investigation was to determine if the efficacy of amoxicillin-clavulanate against penicillin-resistant Streptococcus pneumoniae could be improved by increasing the pediatric amoxicillin unit dose (90 versus 45 mg/kg of body weight/day) while maintaining the clavulanate unit dose at 6.4 mg/kg/day. A rat pneumonia model was used. In that model approximately 6 log10 CFU of one of four strains of S. pneumoniae (amoxicillin MICs, 2 microg/ml [one strain], 4 microg/ml [two strains], and 8 microg/ml [one strain]) were instilled into the bronchi of rats. Amoxicillin-clavulanate was given by computer-controlled intravenous infusion to approximate the concentrations achieved in the plasma of children following the administration of oral doses of 45/6.4 mg/kg/day or 90/6.4 mg/kg/g/day divided every 12 h or saline as a control for a total of 3 days. Infusions continued for 3 days, and 2 h after the cessation of infusion, bacterial numbers in the lungs were significantly reduced by the 90/6.4-mg/kg/day equivalent dosage for strains for which amoxicillin MICs were 2 or 4 microg/ml. The 45/6.4-mg/kg/day equivalent dosage was fully effective only against the strain for which the amoxicillin MIC was 2 microg/ml and had marginal efficacy against one of the two strains for which amoxicillin MICs were 4 microg/ml. The bacterial load for the strain for which the amoxicillin MIC was 8 microg/ml was not reduced with either dosage. These data demonstrate that regimens which achieved concentrations in plasma above the MIC for at least 34% of a 24-h dosing period resulted in significant reductions in the number of viable bacteria, indicating that the efficacy of amoxicillin-clavulanate can be extended to include efficacy against less susceptible strains of S. pneumoniae by increasing the amoxicillin dose.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Microbial Sensitivity Tests; Penicillin Resistance; Pneumococcal Infections; Rats; Rats, Sprague-Dawley; Respiratory Tract Infections; Streptococcus pneumoniae

High doses of amoxicillin, equivalent to those produced by 500- and 750-mg oral doses in humans (area under the plasma concentration-time curve), were effective against a penicillin-resistant strain of Streptococcus pneumoniae in an experimental respiratory tract infection in immunocompromised rats; this superior activity confirms the results of previous studies. An unexpected enhancement of amoxicillin's antibacterial activity in vivo against penicillin-resistant and -susceptible S. pneumoniae strains was observed when subtherapeutic doses of amoxicillin were coadministered with the beta-lactamase inhibitor potassium clavulanate. The reason for this enhancement was unclear since these organisms do not produce beta-lactamase. The differential binding of clavulanic acid and amoxicillin to penicillin-binding proteins may have contributed to the observed effects.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Area Under Curve; Colony Count, Microbial; Drug Therapy, Combination; Lung; Male; Penicillin Resistance; Pneumococcal Infections; Rats; Respiratory Tract Infections; Streptococcus pneumoniae

Topics: Amoxicillin-Potassium Clavulanate Combination; beta-Lactam Resistance; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Pneumococcal Infections; Streptococcus pneumoniae

The in vivo activities of amoxicillin and amoxicillin-clavulanate against 17 strains of Streptococcus pneumoniae with penicillin MICs of 0.12-8.0 mg/liter were assessed in a cyclophosphamide-induced neutropenic murine thigh infection model. Renal impairment was produced by administration of uranyl nitrate to prolong the amoxicillin half-life in the mice from 21 to 65 min, simulating human pharmacokinetics. Two hours after thigh infection with 10(5) to 10(6) CFU, groups of mice were treated with 7 mg of amoxicillin per kg of body weight alone or combined with clavulanate (ratio, 4:1) every 8 h for 1 and 4 days. There was an excellent correlation between the MIC of amoxicillin (0.03 to 5.6 mg/liter) and (i) the change in log10 CFU/thigh at 24 h and (ii) survival after 4 days of therapy. Organisms for which MICs were 2 mg/liter or less were killed at 1.4 to 4.2 and 1.6 to 4.1 log10 CFU/thigh at 24 h by amoxicillin and amoxicillin-clavulanate, respectively. The four strains for which MICs were >4 mg/liter grew 0.2 to 2.6 and 0.6 to 2. 3 logs at 24 h despite therapy with amoxicillin and amoxicillin-clavulanate, respectively. Infection was uniformly fatal by 72 h in untreated mice. Amoxicillin therapy resulted in no mortality with organisms for which MICs were 1 mg/liter or less, 20 to 40% mortality with organisms for which MICs were 2 mg/liter, and 80 to 100% mortality with organisms for which MICs were 4.0-5.6 mg/liter. Lower and higher doses (0.5, 2, and 20 mg/kg) of amoxicillin were studied against organisms for which MICs were near the breakpoint. These studies demonstrate that a reduction of 1 log10 or greater in CFU/thigh at 24 h is consistently observed when amoxicillin levels exceed the MIC for 25 to 30% of the dosing interval. These studies would support amoxicillin (and amoxicillin-clavulanate) MIC breakpoints of 1 mg/liter for susceptible, 2 mg/liter for intermediate, and 4 mg/liter for resistant strains of S. pneumoniae.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Animals; Drug Therapy, Combination; Female; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Penicillins; Pneumococcal Infections; Streptococcus pneumoniae

This study tested 212 pneumococcal isolates from 9 institutions for their susceptibilities to penicillin, ampicillin, amoxycillin, amoxycillin/clavulanate, cefaclor, cefuroxime, cefotaxime, imipenem, tetracycline, erythromycin, and clarithromycin using NCCLS-standardized microdilution. Penicillin-insusceptibility was 12.3% [5.7% intermediate (0.12-1 microgram/ml) and 6.6% high-level (> or = 2 micrograms/ml)], tetracycline-insusceptibility (> or = 4 micrograms/ml) 31.1%, and erythromycin-insusceptibility (> or = 0.5 microgram/ml) 31.1% as well. Erythromycin-insusceptible isolates showed cross-insusceptibility to clarithromycin. Penicillin-susceptible isolates were susceptible to all beta-lactams. MICs of all beta-lactams rose with those of penicillin for penicillin-insusceptible isolates. Ampicillin and penicillin were equally potent against penicillin-insusceptible isolates, imipenem, cefotaxime, and amoxycillin +/- clavulanate were more potent (generally 5, 1, and 1 doubling dilution, respectively), and cefuroxime and cefaclor less potent (generally 1 and 6 doubling dilutions, respectively). Most penicillin-insusceptible isolates were high-level resistant to cefaclor (> or = 32 micrograms/ml). Although MICs of all beta-lactams rose with those of penicillin, resistance to penicillin was not absolute in terms of cross-resistance. Most penicillin-intermediate and high-level penicillin-resistant isolates remained fully susceptible and intermediate, respectively, to amoxycillin +/- clavulanate, cefotaxime, and imipenem, but not to cefuroxime. Penicillin-susceptible isolates were 76.9%, 42.3%, and 34.6% co-insusceptible to tetracycline, erythromycin, and tetracycline plus erythromycin, respectively. Most penicillin-, tetracycline-, and erythromycin-insusceptible isolates were of capsular types 23 >> 6 > 19 > 32, 19 > 6 > 28 > 23, and 19 > 6 > 14 > 23, respectively. Compared to winter 1994-1995, insusceptibility to penicillin, tetracycline, and erythromycin rose by some 4%, 4%, and 13%, respectively.

Topics: Adolescent; Adult; Amoxicillin-Potassium Clavulanate Combination; Ampicillin Resistance; Anti-Bacterial Agents; Belgium; Cephalosporin Resistance; Child; Child, Preschool; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Macrolides; Middle Aged; Penicillin Resistance; Pneumococcal Infections; Population Surveillance; Streptococcus pneumoniae; Tetracycline Resistance; Thienamycins

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Infective Agents; Cefuroxime; Cephalosporins; Doxycycline; Drug Therapy, Combination; Fluoroquinolones; Humans; Naphthyridines; Ofloxacin; Outpatients; Penicillin G; Penicillins; Piperazines; Pneumococcal Infections; Quinolones; Roxithromycin; Streptococcus pneumoniae

Primary peritonitis caused by Streptococcus pneumoniae is a rare but serious complication of childbirth. We present here three cases of young women who developed abdominal pain after childbirth. All of the patients had fever with abdominal pain, diarrhea and clinical signs of peritonitis. In two cases a laparotomy was performed to remove pus. Cultures taken were positive for Streptococcus pneumoniae. Culture of vaginal swabs and blood cultures were also positive for the same pathogen. For the third patient, both vaginal swabs and blood cultures were positive for Streptococcus pneumoniae, antibiotic therapy only was administered. Outcome was favorable for all. We discuss the pathogenesis, clinical presentation, management and the usefulness for systematic search "for" Streptococcus pneumoniae in vaginal swabs.

Topics: Abdominal Pain; Adult; Amikacin; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteremia; Cilastatin; Diarrhea; Drug Therapy, Combination; Female; Fever; Humans; Imipenem; Laparotomy; Penicillins; Peritonitis; Pneumococcal Infections; Protease Inhibitors; Puerperal Infection; Thienamycins; Treatment Outcome; Vagina

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Child; Child, Preschool; Clavulanic Acids; Drug Resistance, Microbial; Drug Therapy, Combination; Europe; Female; Humans; Infant; Israel; Male; Microbial Sensitivity Tests; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae; United States