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Dermatologists treat a variety of uncomplicated skin and skin structure infections (uSSSIs) such as folliculitis, impetigo, erysipelas, cellulitis, furuncles, carbuncles, and non-perirectal abscesses. Most uSSSIs are caused by Staphylococcus aureus and Streptococcus pyogenes. The new extended-spectrum cephalosporins (cefdinir, cefpodoxime) offer efficacy against most Gram-positive and Gram-negative pathogens. Despite recently published guidelines, many physicians do not prescribe cephalosporins for uSSSIs out of concern that these agents will produce a hypersensitivity reaction in patients allergic to penicillin. Although the rate of cephalosporin reaction in penicillin-allergic patients is often quoted as up to 10%, this rate does not take into account the 1% to 3% risk for allergy to cephalosporin alone and the nonspecific increased risk of penicillin-allergic patients to develop hypersensitivity to other drugs. When these additional risks are considered, the likelihood of a reaction in known penicillin-allergic patients, especially to most third-generation and extended spectrum cephalosporins, becomes less than 1%. Cephalosporins with side chains unlike those of penicillin or ampicillin side chains are less likely to result in an allergic reaction in penicillin or ampicillin-allergic patients than cephalosporins with similar side chains. Although both cefdinir and cefpodoxime are considered to carry a very low risk of cross reactivity with penicillin or ampicillin, the former demonstrates better activity against S. aureus. Among the late-generation cephalosporins, cefdinir is the most potent oral agent when tested against oxacillin-susceptible staphylococci, 4- to 16-fold more active than cefprozil and cephalexin, respectively.
Because of increasing resistance to older antimicrobial agents, newer drugs need to be evaluated for the treatment of skin and skin-structure infections (SSSIs). This double-masked, randomized, comparative, multicenter study enrolled patients aged 13 years or older with SSSIs to receive either cefdinir 300 mg BID or cephalexin 500 mg QID for 10 days. Nine hundred fifty-two patients (474 in the cefdinir group and 478 in the cephalexin group) took part, primarily white males between 18 and 65 years of age. There were two follow-up visits, with efficacy determined at the test-of-cure visit, 7 to 16 days posttherapy. Many patients were not microbiologically assessable, primarily because of negative cultures at study admission. Patients who required surgical intervention (e.g., incision and drainage) at the site of infection more than 24 hours after the initiation of drug therapy were defined as treatment failures. Significantly more isolated pathogens were resistant to cephalexin than to cefdinir. In the 178 efficacy-assessable cefdinir-treated patients, the rate of pathogen eradication was 93% (200/215), and the rate of successful clinical response was 88% (157/178), compared with 89% (221/247) and 87% (177/204), respectively, in the 204 efficacy-assessable cephalexin-treated patients. Using confidence-interval analysis, the microbiologic and clinical response rates of the cefdinir-treated patients were statistically equivalent to those of the cephalexin-treated patients. At the follow-up visits, patients were questioned about any adverse events occurring since their previous visit. Any untoward symptom occurring during or within 2 days after completion of drug treatment was considered an adverse reaction if the investigator judged it to be definitely, probably, or possibly related to the study drug. One hundred twenty-three (26%) cefdinir-treated patients and 77 (16%) cephalexin-treated patients experienced at least one adverse reaction, a statistically significant difference. Study drug was discontinued for adverse reactions in 20 (4%) cefdinir-treated patients and 13 (3%) cephalexin-treated patients; in the two groups, 10 and 7 patients, respectively, were discontinued for diarrhea. Cefdinir taken BID was as effective as cephalexin taken QID in the treatment of mild-to-moderate SSSIs and was well tolerated by most patients. The increased antibacterial activity of cefdinir must be balanced against the higher rate of diarrhea seen in patients treated with this drug.
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To evaluate prevalence of ss-lactamase nonproducing ampicillin-resistant (BLNAR) strains of Haemophilus influenzae with mutations in ftsI gene encoding penicillin-binding protein 3 (PBP3) among children with otitis media.
We analyzed the National Ambulatory Medical Care Survey, 2002-2006 (N = 1114), which occurred in US physicians' offices. The patients were children aged 6 months to 12 years who were diagnosed with AOM. The time comparisons were the 30-month periods before and after the guideline. The main outcome was the encounter rate at which no antibiotic-prescribing was reported. Secondary outcomes were the identification of factors associated with encounters at which no antibiotic-prescribing was reported and antibiotic- and analgesic-prescribing rates.
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Amoxicillin would still be advocated therefore as being a suitable first-line agent, while reduced susceptibility of Prevotella strains remains a matter of concern with penicillins. Amoxicillin/clavulanate, clindamycin, and metronidazole are useful alternatives in combating the anaerobic bacteria involved in dentoalveolar infection.
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Farnesol is a promising adjuvant agent against S. aureus skin infections treated with beta-lactam antibiotics. Further, 5% xylitol inhibited glycocalyx production by S. aureus cells and consequently had a suppressive effect on the colonization of S. aureus on the horny cells of AD lesions.
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Open label noncomparative trial.
Seven extended-spectrum beta-lactamases related to TEM and four enzymes derived from SHV-1 were transferred to a common Escherichia coli host so that the activity of a variety of beta-lactams could be tested in a uniform genetic environment. For most derivatives, penicillinase activity was 10% or less than that of strains making TEM-1, TEM-2, or SHV-1 beta-lactamase, suggesting that reduced catalytic efficiency accompanied the broader substrate spectrum. Despite this deficit, resistance to aztreonam, carumonam, cefdinir, cefepime, cefixime, cefmenoxime, cefotaxime, cefotiam, cefpirome, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, cefuroxime, and E1040 was enhanced. For strains producing TEM-type enzymes, however, MICs of carumonam, cefepime, cefmenoxime, cefotiam, cefpirome, and ceftibuten were 8 micrograms/ml or less. Susceptibilities of cefmetazole, cefotetan, cefoxitin, flomoxef, imipenem, meropenem, moxalactam, temocillin, FCE 22101, and Sch 34343 were unaffected. FCE 22101, imipenem, meropenem, and Sch 34343 were inhibitory for all strains at 1 microgram/ml or less. In E. coli an OmpF- porin mutation in combination with an extended-spectrum beta-lactamase enhanced resistance to many of these agents, but generally by only fourfold. Hyperproduction of chromosomal AmpC beta-lactamase increased resistance to 7-alpha-methoxy beta-lactams but not that to temocillin. When tested at 8 micrograms/ml, clavulanate was more potent than sulbactam or tazobactam in overcoming resistance to ampicillin, while cefoperazone-sulbactam was more active than ticarcillin-clavulanate or piperacillin-tazobactam, especially against TEM-type extended-spectrum beta-lactamases.
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In order to investigate penicillin resistance (Pcr) in Streptococcus pneumoniae from clinical sources in Japan, a total 1,127 strains of S. pneumoniae was collected at random from 36 institutions participating to "Working group for Pcr S. pneumoniae" around the country in 1993-1994. These strains were isolated more frequently from sputum (38.2%), throat (31.4%), nasal discharge (16.4%), and otorrhea (5.7%). A small number of isolates from blood (19 strains; 1.8%), cerebrospinal fluid (11 strains; 1.0%), and pleural fluid (2 strains; 0.2%) were included respectively. Patients from whom S. pneumoniae was isolated have mostly been associated with children < or = 12 years of age and adults 60 < or = years olds. These isolates were tested for susceptibility to penicillin G, ampicillin, oxacillin, cefixime, cefdinir, imipenem, panipenem, erythromycin, clindamycin, minocycline, and vancomycin by an agar dilution method using Mueller Hinton agar supplemented with 10% sheep blood. Strains with the MICs > or = 0.125 micrograms/ml for penicillin G were defined as a Pc resistance. Of the 1,127 strains, 471 strains (41.8%) were identified as a Pc resistance. Pcr S. pneumoniae were almost resistant to other beta-lactams, including ampicillin, oxacillin, ceftizoxime, cefixime, cefdinir. Although, the MICs of imipenem and panipenem ragned from 0.004-2.0 micrograms/ml with 2 peaks distributions, these antibiotics inhibited the growth of most of Pcr S. pneumoniae at the lowest concentrations of < or = 0.5 microgram/ml. Only vancomycin resistant strain was not detected in these isolates. Most of the Pcr strains were simultaneously resistant to macrolides and minocycline. Further more, isolation frequencies of Pcr S. pneumoniae in west Japan, were relatively high compared with those of east Japan.
Ciprofloxacin-resistant Escherichia coli isolates (n = 1,858) from outpatient midstream urine specimens at 40 North American clinical laboratories in 2004 to 2005 were frequently resistant to ampicillin (79.8% of isolates) and trimethoprim-sulfamethoxazole (66.5%); concurrent resistance to cefdinir (9.0%) or nitrofurantoin (4.0%) was less common. Only 10.8% of isolates were resistant to ciprofloxacin alone. Fluoroquinolone-resistant isolates of E. coli from urine were frequently multidrug resistant.
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Facial vein thrombophlebitis is an uncommon complication of sinusitis. In cases where periorbital swelling complicating sinusitis is diagnosed, clinical findings of swelling and erythema extending beyond the orbital region into the cheek should alert the physician about this unusual complication and the need for further contrast-enhanced imaging and venography. The radiologist must be particularly careful in the evaluation of vascular structures of the face and neck in these children. CT and MRI with contrast material and MR venography are studies that clearly demonstrate the vascular anatomy and possible complications. However, MR venography confirms flow abnormalities within the venous system with the advantage of avoiding radiation exposure to the pediatric patient.
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Fever was reduced and GABHS was eradicated more rapidly from children treated with cefdinir as compared to amoxicillin.
Cephalosporins were found to be more effective than penicillins in the eradication of group A beta-hemolytic streptococcal (GABHS) from tonsillar tissues. This study investigated the effect of amoxicillin and cefdinir therapies on the rate of eradication of GABHS from the tonsils of children with acute pharyngo-tonsillitis (PT).
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Comparative, investigator-blinded multicenter trial.
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In this randomized, double-blind, placebo-controlled trial, we randomly assigned Malawian children, 6 to 59 months of age, with severe acute malnutrition to receive amoxicillin, cefdinir, or placebo for 7 days in addition to ready-to-use therapeutic food for the outpatient treatment of uncomplicated severe acute malnutrition. The primary outcomes were the rate of nutritional recovery and the mortality rate.
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The mucoadhesive microcapsules were prepared by using various concentrations of three different mucoadhesive polymers, namely, chitosan, Carbopol 934P, and methyl cellulose as wall materials and cefdinir as the core material employing orificeionic gelation method. The prepared microcapsules were characterized by scanning electron microscope (SEM) and Fourier transform infrared spectrometry (FT-IR). The prepared microcapsules were found to be spherical with particle size ranging from 765±20 to 985±10 μm and encapsulation efficiencies in the range of 55%-92%. The formulation containing Carbopol 934P as mucoadhesive polymer was found to be best with particle size 946±10 μm. The ex vivo wash-off test showed that the mucoadhesion after 1 h was 80% and the in vitro drug release was extended for more than 12 h. FT-IR spectra indicate that there was no interaction between drug and the polymers used in the formulation. Cefdinir is better absorbed from the upper part of the gastrointestinal tract, it suffers from low oral bioavailability (20-30%), shorter biological half-life (1-2 h), and less transit time. Thus, it can be concluded that microcapsules prepared using Carbopol 934P have promising properties for use as mucoadhesive carrier to increase the residence time of cefdinir.
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The present report presents two cases of confluent and reticulate papillomatosis. Case 1 was a 24-year-old man who had suffered from skin eruptions for six months, and Case 2 was a 19-year-old woman who had had this disease for three days. In both patients, reticular dark brown papules, accompanied by mild keratosis and infiltration, spread from the trunk to the neck and upper arm. Direct light microscopy did not detect the presence of any fungi, and histopathological examinations confirmed hyperkeratosis, acanthosis, papillomatosis, and mild small-round-cell infiltration. Thus, these patients were diagnosed as confluent and reticulate papillomatosis. Neither one had diabetes or thyroid dysfunction. In Case 1, cefdinir was effective, and in Case 2, minocycline hydrochloride and ketoconazole were effective. To the best of our knowledge, this was the first documented case of confluent and reticulate papillomatosis responding to cefdinir.
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The in vitro activities (MIC and MBC) of telithromycin (HMR 3647) against clinical isolates in Japan were investigated in comparison with those of erythromycin A, clarithromycin, azithromycin, amoxycillin, cefdinir and levofloxacin. Telithromycin was more potent than the reference compounds against erythromycin A-susceptible or resistant Streptococcus pneumoniae isolates possessing either mef (mefA or mefE) genes or the ermB gene. Against erythromycin A-susceptible or inducibly resistant Staphylococcus aureus and erythromycin A-susceptible and intermediate Enterococcus faecalis, telithromycin was highly active.
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The clinical efficacy and safety of clarithromycin (CAM) and cefdinir (CFDN) were evaluated in 65 pediatric outpatients with group A beta-hemolytic streptococcal tonsillopharyngitis. Treatment was "effective" or better in 26 (78.8%) children receiving CAM and in 27 (87.1%) receiving CFDN based on antigen clearance and the "Criteria for Evaluation in Clinical Trials of Antibacterial Agents in Children" proposed by Japan Society of Chemotherapy (p = NS). The causative organisms were eradicated in 94.7% and 93.8% of subjects in the CAM and CFDN groups, respectively (p = NS). Adverse drug reactions were limited to moderate diarrhea in one patient in each group, and subsided during treatment. Causative organisms exhibited good susceptibility to CAM and CFDN. These results suggest excellent efficacy, safety and usefulness of CAM and CFDN in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitsis in children.
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Assessing elderly patients suspected of the HI infection, and organized management for treatment are essential to improving outcome.
The effect of serum on the bactericidal activity of cefdinir, and the ability of the antibiotic to modify the interaction of bacteria with human polymorphonuclear neutrophils were assessed. In the presence of antibiotic, serum-resistant Escherichia coli were sensitised to the bactericidal activity of normal human serum. Cefdinir enhanced opsonophagocytic killing of Escherichia coli and Staphylococcus aureus at suprainhibitory concentrations. Significant potentiation of killing occurred with the combination of inhibitory concentrations of cefdinir, neutrophils and sub-optimal levels of serum opsonins. Pre-exposure of Escherichia coli, but not Staphylococcus aureus, to cefdinir enhanced phagocytic uptake and killing of the antibiotic-damaged bacteria. These results indicate that cefdinir-mediated phenotypic modification of Escherichia coli renders the bacteria susceptible to serum antibacterial activity and phagocytic uptake and intracellular killing.
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Of 447 children enrolled, 230 were clinically and bacteriologically evaluable (74% 2 years old or younger; 57% treated for AOM in previous 3 months). Bacteriologic eradication, based on repeat tympanocentesis on days 4-6, was achieved in 74% (170 of 230) of children; 76% (201 of 266) of AOM pathogens were eradicated. Eradication of penicillin-susceptible, -intermediate and -resistant S. pneumoniae was 91% (50 of 55), 67% (18 of 27) and 43% (10 of 23), respectively (P < 0.001); eradication of H. influenzae was 72% (90 of 125). Overall clinical response at days 12-14 was 83% (76 and 82% for children with S. pneumoniae and Haemophilus influenzae, respectively). Sustained clinical response at days 25-28 was 85%. Clinical response was 83% for culture-positive children versus 96% for culture-negative children at baseline tympanocentesis (P < 0.001).
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The clinical efficacy of cefditoren pivoxil (CDTR-PI) was evaluated for 43 pediatric patients with acute otitis media or acute sinusitis. The causative organisms were identified and their susceptibilities to 6 oral beta-lactam antibiotics were measured; ampicillin (ABPC), cefaclor (CCL), cefdinir (CFDN), cefditoren pivoxil (CDTR-PI), cefteram pivoxil (CFTM-PI) and cefpodoxime proxetil (CPDX-PR). The ages of 43 patients were distributed from 4 months to 10 years and 7 months, and especially children under 4 years accounted for 72% (31 cases). In 22 cases (51%), Haemophilus influenzae or Streptococcus pneumoniae were identified as the pathogens, but in 18 cases, no causative organisms were defined. Treatment by CDTR-PI was successful in 12 cases out of 15 evaluable cases in which H. influenzae or S. pneumoniae were identified as the main causative organisms. From the susceptibility testing of them, some strains of H. influenzae were found to be ABPC-resistant and some strains of S. pneumoniae were benzylpenicillin (PCG)-resistant. To support above clinical evaluation of CDTR-PI, susceptibility testings on clinically isolated H. influenzae (81 strains) and S. pneumoniae (79 strains) were performed using above mentioned 6 oral beta-lactam antibiotics. The MIC80s against H. influenzae were; CDTR-PI 0.06 microgram/ml, CCL 2 micrograms/ml, CPDX-PR 0.125 microgram/ml, CFTM-PI 0.03 microgram/ml, CFDN 1 microgram/ml and ABPC 1 microgram/ml. Those against S. pneumoniae were; CDTR-PI 0.5 microgram/ml, CCL > 4 micrograms/ml, CPDX-PR 2 micrograms/ml, CFTM-PI 1 microgram/ml, CFDN 2 micrograms/ml and ABPC 1 microgram/ml. From those results, it was concluded that CDTR-PI or CFTM-PI may be preferable for the treatment of acute otitis media and acute sinusitis in children.
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Beta-lactamase-producing (BLP) strains having the bla gene were identified in 16 isolates (2.5%). PGM strains were identified in 279 isolates (43.3%). There were 242 PGM1-non-BLP strains (37.6%) with mutations in the variable mutated locus of ftsI, 35 PGM2-non-BLP strains (5.4%) with mutations in the highly mutated locus of ftsI and 2 BLP-PGM strains (0.3%) with mutations in ftsI that produced beta-lactamase. BLP-non-PGM strains producing beta-lactamase without mutations in ftsI were identified in 14 isolates (2.2%). MICs of PGM1-non-BLP strains to AMP were 0.5-2.0 microg/ml. The MIC90 of CDN to the PGM1-non-BLP strains was the lowest (0.06 microg/ml). The proportion of PGM1-non-BLP strains increased rapidly during 1999-2002 and then decreased in 2003. In contrast, the proportion of PGM2-non-BLP strains increased in 2003.
The spectrum and potency of cefdinir, an orally administered cephalosporin, was reevaluated for the uncomplicated skin and soft tissue infection (uSSTI) indication using contemporary isolates from 2004 to 2005. Cefdinir continues to have high rates of susceptibility against methicillin-susceptible staphylococci (100.0%), beta-hemolytic streptococci (groups A and B; 100.0%), viridans group streptococci (88.9%), Escherichia coli (93.2%), and Klebsiella pneumoniae (90.0%). No diminished activity was detected since the last evaluation (1997-2002 isolates), and cefdinir remains significantly more potent (4- to 16-fold) than cephalexin, even when using surrogate agents of cephalexin susceptibility that were suspect for estimating true clinical utility. Activity greater than cephalexin (4-fold) was also noted for cefdinir against community-associated methicillin-resistant Staphylococcus aureus isolates. Cefdinir should be considered as a viable option for the therapy uSSTI caused by indicated species.
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Cefditoren and other orally administered cephalosporins are infrequently included in resistance surveillance studies. Here we evaluated 359 contemporary (2004-2006) strains of Streptococcus pneumoniae, including penicillin-intermediate (12.0%) and -resistant (22.8%) subsets from United States patients by reference broth microdilution methods. Cefditoren was the most potent cephalosporin tested (MIC(50), 0.015 mg/L), including against penicillin-intermediate strains (MIC(50), 0.12 mg/L), and was two-, four- and eight-fold more active than cefuroxime, cefdinir and cefprozil, respectively. Penicillin-resistant strains were largely resistant to all tested ss-lactams. We confirm the continued spectrum and potency for cefditoren against S. pneumoniae that surpasses that of other orally administered cephalosporins.
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A COX inhibitor had an effect on vascular permeability in CNV and may have improved exudative changes.
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We conducted a retrospective cohort study of children aged 6 months to 6 years and received their first diagnosis of UTI in a network of 27 outpatient pediatric practices between July 1, 2001, and May 31, 2006. We examined the relationship between antimicrobial resistance in UTI isolates and exposure to specific antimicrobial agents (amoxicillin, amoxicillin-clavulanate, cefdinir, trimethoprim-sulfamethoxazole, and azithromycin) in the previous 120 days. We developed multivariable logistic regression models for resistance to ampicillin, amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, and first-generation and third-generation cephalosporins, adjusting for potential confounders such as age, number of siblings, recent hospitalizations, and child care exposure.
The purpose of this study was to evaluate various oral antimicrobial agent levels in tooth extraction sites.
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To examine the microbiologic and clinical efficacy of a 5-day course of cefdinir in the treatment of tympanocentesis-documented acute otitis media (AOM).