Search PubMed⌕ Search

Biomedical subjects

J M McCarty

Publications and source records attributed to J M McCarty.

At least 19 recordsLinked to original sources

PEPCK mRNA localization in proximal tubule and gene regulation during metabolic acidosis.

To identify the nephron segments expressing PEPCK in control and acidotic conditions, PEPCK mRNA was localized in rat kidney using the technique of reverse transcription and polymerase chain reaction (RT-PCR) in individual microdissected S1 S2, and S3 segments of the rat proximal tubule. In controls, the number of tubules expressing PEPCK mRNA was greatest in the S3 segment, moderate in the S2 segment, and least in the S1 segment of the proximal tubule. After NH4Cl feeding, strong signals for PEPCK mRNA were detected in all three proximal tubule segments. In situ hybridization demonstrated expression of PEPCK mRNA only in the medullary rays in controls. After NH4Cl, PEPCK mRNA was expressed throughout the cortex, confirming the RT-PCR results. These data demonstrate the ability of the rat kidney cortex to modulate the expression of PEPCK mRNA during metabolic acidosis by recruitment of additional cells in the proximal nephrons. Studies with cultured LLC-PK1-F+ cells indicated that increased PEPCK gene transcription at acid pH required a cis-acting element (enhancer) in the more distal 5' flanking region of the promoter.

Acidosis↗

Five days of cefprozil versus 10 days of clarithromycin in the treatment of an acute exacerbation of chronic bronchitis.

BACKGROUND: Shorter than traditional 7- to 14-day treatment regimens have demonstrated efficacy in treatment of an acute exacerbation of chronic bronchitis (AECB). OBJECTIVE: Perform a clinical efficacy study comparing 5 days of cefprozil therapy to 10 days of clarithromycin in treating an AECB. METHODS: A multicenter, randomized, double-blind study comparing efficacy and safety of cefprozil, 500 mg twice daily, for 5 days with clarithromycin, 500 mg twice daily, for 10 days in treatment of 295 subjects with AECB. Concomitantly, among all treated subjects, 39% (115 of 295) had a history of chronic obstructive pulmonary disease/emphysema; 21% (62 of 295) had a history of asthma/reactive airway disease; and 31% (90 of 295) had environmental allergies. RESULTS: There were no statistically significant differences among clinically evaluable subjects' cure rates; 82% (109 of 133) treated with cefprozil versus 85% (105 of 123) treated with clarithromycin were cured at test-of-cure visit (95% confidence interval, -12.0 to 5.1%). Clinical cure rates at end of study were 80% and 81%, respectively (95% confidence interval, -10.8 to 7.9%). Before treatment, 99% (85 of 86) of Gram-positive organisms isolated were susceptible to cefprozil and 78% (67 of 86) were susceptible to clarithromycin. A total of 84% (96 of 114) of Gram-negative organisms were susceptible to cefprozil and 63% (72 of 114) were susceptible to clarithromycin. Of clinically evaluable Streptococcus pneumoniae-infected subjects, 100% (11 of 11) of cefprozil subjects and 93% (14 of 15) of clarithromycin subjects experienced clinical cure. The most frequently reported adverse effects were nausea, 5% (7 of 150), and diarrhea, 9% (14 of 150), for cefprozil. For clarithromycin, the adverse effects were nausea, 8% (11 of 145); diarrhea, 12% (18 of 145); taste perversion, 8% (11 of 145); and dry mouth, 5% (7 of 145). CONCLUSIONS: Five days of cefprozil is as effective as 10 days of clarithromycin for treatment of an AECB.

Adult↗

Neuronal nitric oxide synthase: expression in rat parietal cells.

Nitric oxide synthases (NOS) are enzymes that catalyze the generation of nitric oxide (NO) from L-arginine and require nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor. At least three isoforms of NOS have been identified: neuronal NOS (nNOS or NOS I), inducible NOS (iNOS or NOS II), and endothelial NOS (eNOS or NOS II). Recent studies implicate NO in the regulation of gastric acid secretion. The aim of the present study was to localize the cellular distribution and characterize the isoform of NOS present in oxyntic mucosa. Oxyntic mucosal segments from rat stomach were stained by the NADPH-diaphorase reaction and with isoform-specific NOS antibodies. The expression of NOS in isolated, highly enriched (>98%) rat parietal cells was examined by immunohistochemistry, Western blot analysis, and RT-PCR. In oxyntic mucosa, histochemical staining revealed NADPH-diaphorase and nNOS immunoreactivity in cells in the midportion of the glands, which were identified as parietal cells in hematoxylin and eosin-stained step sections. In isolated parietal cells, decisive evidence for nNOS expression was obtained by specific immunohistochemistry, Western blotting, and RT-PCR. Cloning and sequence analysis of the PCR product confirmed it to be nNOS (100% identity). Expression of nNOS in parietal cells suggests that endogenous NO, acting as an intracellular signaling molecule, may participate in the regulation of gastric acid secretion.

Animals↗

Clarithromycin in the management of community-acquired pneumonia.

OBJECTIVE: To review the epidemiology and diagnosis of community-acquired pneumonia (CAP) and examine factors that influence the choice of empiric antimicrobial therapy. BACKGROUND: CAP remains a common disease with substantial associated morbidity and mortality. Outpatient management of patients with CAP has become increasingly complex because of the availability of newer antimicrobial agents, evolving patterns of resistance, and the increasing recognition of atypical pathogens. Although Streptococcus pneumoniae remains a commonly encountered pathogen, the development and increasing prevalence of antibiotic resistance has become an area of concern, especially in outpatients. The newer macrolide antimicrobial drugs-clarithromycin and azithromycin-are effective against commonly encountered pathogens, are well tolerated, and have an established tolerability profile, although the low serum levels achieved by azithromycin hinder its use in patients with suspected bacteremia. METHODS: A MEDLINE search was performed of English-language articles published from 1990 to 2000 on the treatment of CAP. This article reviews the treatment of CAP, with emphasis on the use of clarithromycin. CONCLUSION: Although laboratory surveillance studies have reported macrolide-resistant S. pneumoniae, recent evidence defining the mechanism of this resistance, coupled with the pharmacokinetic properties of the macrolide agents, suggests that the actual rate of clinical macrolide resistance is low.

Anti-Bacterial Agents↗

Comparative safety and efficacy of cefdinir vs amoxicillin/clavulanate for treatment of suppurative acute otitis media in children.

OBJECTIVE: Two dosage regimens of cefdinir were compared with amoxicillin/clavulanate for the treatment of suppurative acute otitis media (AOM) in children. METHODS: This was an investigator-blinded, randomized, comparative, multicenter trial, in which tympanocentesis was performed in 384 patients, ages 6 months to 12 years, who had nonrefractory AOM. Patients were randomized to receive one of three 10-day treatment regimens: cefdinir 14 mg/kg daily (QD; n = 128); cefdinir 7 mg/kg twice a day (BID; n = 128); or amoxicillin/clavulanate 40/10 mg/kg/day divided for use three times a day (TID; n = 128). RESULTS: Of the 384 enrolled patients 303 were evaluable for clinical efficacy. Clinical success rates were statistically equivalent for the 3 treatment groups at the end of therapy: 85 of 102 (83.3%) for cefdinir QD; 81 of 101 (80.2%) for cefdinir BID; 86 of 100 (86%) for amoxicillin/clavulanate. Of the 197 evaluable patients from whom a susceptible pathogen was recovered, presumptive eradication rates at end of therapy were equivalent: 55 of 65 (84.6%), 54 of 66 (81.8%) and 55 of 66 (83.3%) for cefdinir QD-, cefdinir BID- and amoxicillin/clavulanate-treated patients, respectively. However, presumptive eradication rates for Streptococcus pneumoniae were significantly lower for cefdinir BID (55.2%) than for amoxicillin/clavulanate (89.5%; P = 0.0019) and marginally lower than for cefdinir QD (80%; P = 0.054). Diarrhea was the most common treatment-associated adverse reaction in all groups but was significantly more common in amoxicillin/clavulanate-treated patients (35%) than in patients who had been treated with cefdinir QD (10%, P<0.001) or cefdinir BID (13%, P<0.001). CONCLUSIONS: A 10-day regimen of cefdinir 14 mg/kg QD or 7 mg/kg BID was as clinically effective overall as a 10-day regimen of amoxicillin/ clavulanate 40/10 mg/kg/day divided TID in the treatment of tympanocentesis-confirmed, nonrefractory AOM in children. These data suggest that cefdinir QD may be a better alternative than cefdinir BID for refractory AOM. Both dosing regimens of cefdinir were associated with significantly fewer gastrointestinal adverse reactions than was amoxicillin/clavulanate.

Acute Disease↗

A randomized trial of short-course ciprofloxacin, ofloxacin, or trimethoprim/sulfamethoxazole for the treatment of acute urinary tract infection in women. Ciprofloxacin Urinary Tract Infection Group.

PURPOSE: Bladder infections are very common in otherwise healthy women, and short-course antimicrobial treatment appears effective for many episodes of cystitis. This study reports the results of short-course ciprofloxacin, ofloxacin, and trimethoprim/sulfamethoxazole therapy. PATIENTS AND METHODS: We performed a randomized, double-blind study of the efficacy and safety of a 3-day course of oral ciprofloxacin 100 mg twice daily, ofloxacin 200 mg twice daily, or trimethoprim/sulfamethoxazole 160/800 mg twice daily in women with acute, uncomplicated, symptomatic lower urinary tract infection. RESULTS: A total of 866 patients were enrolled, of whom 688 (79%) were evaluated for the efficacy of treatment (229 treated with ciprofloxacin, 228 treated with trimethoprim/sulfamethoxazole, and 231 treated with ofloxacin). The most frequent reason for exclusion was the failure to identify a pretreatment pathogen. The most commonly isolated pathogen was Escherichia coli (81%). Eradication of the pretreatment pathogen at the end of therapy occurred in 94% of ciprofloxacin, 93% of trimethoprim/sulfamethoxazole, and 97% of ofloxacin-treated patients. At follow-up evaluation at 4 to 6 weeks, recurrence rates (relapse or reinfection) were 11% in the ciprofloxacin, 16% in the trimethoprim/sulfamethoxazole, and 13% in the ofloxacin treatment group. Clinical success at the end of therapy was 93% in the ciprofloxacin, 95% in the trimethoprim/sulfamethoxazole, and 96% in the ofloxacin treatment groups. The frequency of all adverse events was 31% for ciprofloxacin, 41% for trimethoprim/sulfamethoxazole, and 39% for ofloxacin-treated patients (P = 0.03). Premature discontinuation of study drug due to an adverse event was more common in trimethoprim/sulfamethoxazole-treated patients (n = 9) compared with those given ciprofloxacin (n = 2) or ofloxacin (n = 1; P = 0.02). CONCLUSION: Ciprofloxacin, ofloxacin, and trimethoprim/sulfamethoxazole had similar efficacy when given for 3 days to treat acute, symptomatic, uncomplicated lower urinary tract infection in women.

Acute Disease↗

Penetration of clarithromycin into middle ear fluid of children with acute otitis media.

OBJECTIVE: To determine the steady state plasma and middle ear fluid concentrations of clarithromycin and its metabolite, 14(R)-hydroxyclarithromycin in 32 pediatric patients with acute otitis media. METHODS: After the sixth dose of a 7.5-mg/kg every-12-h regimen of clarithromycin suspension, tympanocentesis was performed at 2, 4, 8 or 12 hours postdose. Plasma and middle ear fluid samples were assayed for concentrations of clarithromycin and its 14-hydroxy metabolite. RESULTS: Mean middle ear fluid concentrations ranged from 3.0 to 8.3 micrograms/g during the dosing interval for clarithromycin and from 1.5 to 3.8 micrograms/g for 14(R)-hydroxyclarithromycin. The mean middle ear fluid concentrations were consistently greater than corresponding mean plasma concentrations, which ranged from 0.7 to 3.4 micrograms/ml for clarithromycin and from 0.8 to 1.8 micrograms/ml for 14(R)-hydroxyclarithromycin. The ratios of middle ear fluid to plasma concentration appeared to increase during the dosing interval and were 8.8 and 3.8 for clarithromycin and 14(R)-hydroxyclarithromycin, respectively, 12 h after dosing. CONCLUSIONS: Multiple oral doses of clarithromycin suspension produced sustained middle ear fluid concentrations of clarithromycin and 14(R)-hydroxyclarithromycin which exceed the minimum inhibitory concentrations of most otic pathogens.

Acute Disease↗

Development of intralesional therapy with fluorouracil/adrenaline injectable gel for management of condylomata acuminata: two phase II clinical studies.

OBJECTIVES: To evaluate a sustained release chemotherapy for treating condylomata acuminata with an injectable gel containing fluorouracil and adrenaline (5-FU/adrenaline gel). Study 1-- To assess contributions of the components of 5-FU/adrenaline gel to efficacy. Study 2--To assess therapeutic contribution of adrenaline and safety and efficacy of the formulations. DESIGN: Randomised, double blind, placebo controlled studies. SETTING: Private practices and university clinics in the United States. PATIENTS: Men and women with new, recurrent, or refractory external condylomata acuminata. INTERVENTION: Six injections over 8 weeks; follow up visits at weeks 1, 4, 8, and 12. MAIN OUTCOME MEASURES EFFICACY: patient/wart response, times to complete response, recurrence rates. SAFETY: injection reactions, tissue conditions, other adverse events, laboratory studies. RESULTS: Study 1: 132 evaluable patients. Complete response (CR) rate was highest for the 5-FU/adrenaline gel group, followed by the 5-FU/adrenaline solution group, then the 5-FU gel group. 5-FU, adrenaline, and the collagen gel vehicle (in the presence of 5-FU) significantly affected CR and strongly influenced time to CR. The effects of 5-FU and adrenaline were statistically significant. Cutaneous reactions were mild to moderate. Study 2: 187 evaluable patients. Patients treated with 5-FU/adrenaline gel had a significantly higher CR rate and lower cumulative 90 day recurrence rate than those treated with 5-FU gel without adrenaline. Treatments were generally well tolerated, with only three treatment related, serious adverse events. CONCLUSION: 5-FU/adrenaline gel is safe and efficacious for treatment of condylomata acuminata, and when compared with individual or various combinations of components, this formulation provided the greatest therapeutic advantage.

Adolescent↗

Intralesional fluorouracil/epinephrine injectable gel for treatment of condylomata acuminata. A phase 3 clinical study.

BACKGROUND AND DESIGN: A new intralesional sustained-release chemotherapy is under development as a treatment for condylomata acuminata; it is administered as an injectable gel that consists of fluorouracil and epinephrine with a purified bovine collagen as the gellant (fluorouracil/epinephrine gel). In this randomized, double-blind study, we evaluated the safety and efficacy of this intralesional treatment in 401 patients, using 2 active drug formulations (fluorouracil/epinephrine gel and fluorouracil gel alone) and a placebo. Each lesion was injected once a week for up to 6 weeks, and patients were followed up for 3 months. RESULTS: A total of 359 patients with 1926 condylomata underwent evaluation. For all lesions treated with fluorouracil/epinephrine gel, the complete response (CR) rate was 77%. For all patients treated with fluorouracil/epinephrine gel, the CR rate was 61%. The fluorouracil/epinephrine gel was significantly more effective (P < .002) in treating condylomata than the fluorouracil gel without epinephrine (CR rate, 43%); both were superior to placebo (CR rate, 5%). At 3 months after completion of treatment, recurrence rates in patients with CRs were as follows: fluorouracil/epinephrine gel group, 50%; fluorouracil gel group, 58%. No clinically significant drug-related systemic reactions occurred. Finally, the type and severity of local tissue reactions of patients with a positive pretreatment collagen skin test result (6/401 [1.5%]) were similar to those of patients with a negative collagen skin test result. CONCLUSION: The fluorouracil/epinephrine injectable gel is a safe and effective treatment for condylomata acuminata.

Adolescent↗

Murine thrombopoietin mRNA levels are modulated by platelet count.

The activity of the c-Mpl ligand hematopoietic progenitors meets criteria expected for thrombopoietin (TPO). Bio-assays have shown that blood TPO levels are inversely related to platelet mass. We sought to identify the molecular basis for this regulation. To determine if TPO mRNA levels respond to platelet demand, RNA from selected organs of mice with high, normal or low platelet counts was subjected to semiquantitative reverse transcriptase-polymerase chain reaction. Although no differences in TPO mRNA levels between control and treated mice could be detected in liver or kidney, TPO-specific bands were more intense after 25 to 30 polymerase chain reaction cycles in marrow-derived mRNA from thrombocytopenic mice. The TPO-specific bands were less intense in thrombocytotic mouse marrow and spleen than control mouse marrow and spleen after 30 cycles. These data support the hypothesis that TPO levels are regulated, at least in part, by modulating mRNA levels in response to platelet demand.

Animals↗

Interleukin-4 induces endothelial vascular cell adhesion molecule-1 (VCAM-1) by an NF-kappa b-independent mechanism.

While all features of the inflammatory response induced by IL-1 are not observed following IL-4 stimulation, suboptimal concentrations both cytokines result in synergistic VCAM-1 expression in HUVEC. We have shown that, while IL-1 stimulated HUVEC express GM-CSF, tissue factor and VCAM-1, only VCAM-1 is detectable after exposure to IL-4. While kB was found essential for both basal and IL-1-mediated activity of VCAM-1, IL-4 induction was kB-independent. Inducible kB-binding proteins were identified in IL-1-, but not IL-4-stimulated nuclear extracts. Our results indicate that IL-4 exerts its transcriptional effects on the VCAM-1 gene through element(s) which do not require kB.

Cells, Cultured↗

Coordinate regulation of multiple human lymphokine genes by Oct-1 and potentially novel 45 and 43 kDa polypeptides.

The hematologic response to inflammation is critically dependent on the release of a family of glycoproteins termed CSFs. Central to this process is the coordinated T lymphocyte production of three of these proteins, granulocyte macrophage-CSF (GM-CSF), IL-3, and IL-5. In the course of our studies of the transcriptional regulation of IL-3 expression we noted that the same or similar proteins that bound to the downstream-activating region of the human IL-3 gene were also captured using DNA probes derived from sequences present in the GM-CSF and IL-5 genes. In this study, DNA-protein cross-linking techniques and reporter gene analyses were used to define the nuclear proteins that mediate transcriptional enhancement of these genes at one cis-acting site. These studies establish that Oct-1, a member of the POU family of transcription factors, binds to regions of the GM-CSF, IL-3, and IL-5 promoters and contributes to basal T cell gene transcription. In addition, although the c-jun proto-oncogene product was detected in stimulated human T cells, two additional T cell-specific proteins (45 and 43 kDa) bind to the GM-CSF, IL-3, and IL-5 promoters and are functionally and immunologically distinct from c-jun or OAP40 (jun-D). These proteins contribute to transcriptional enhancement of the IL-3 and GM-CSF genes in stimulated T cells. Together, these data suggest that the coordinate regulation of several lymphokine genes is based on responses to shared proteins. These studies further our understanding of the networks of transcriptionally active proteins responsible for the host response to inflammatory stimuli.

Base Sequence↗

Comparative efficacy and safety of cefprozil versus penicillin, cefaclor and erythromycin in the treatment of streptococcal pharyngitis and tonsillitis.

Cefprozil is a new oral cephalosporin with an enhanced in vitro spectrum of activity that includes group A beta-hemolytic streptococci (GABHS). Four multicenter randomized clinical trials were conducted to compare the clinical efficacy and safety of cefprozil administered once or twice a day for the treatment of mild to moderate GABHS tonsillitis and pharyngitis. A total of 1597 patients were enrolled in the trials. Patient demographics and severity of infection were similar for all treatment groups. In Study 1, cefprozil administered at 20 mg/kg once daily was clinically, in 68 of 76 patients (89%) and bacteriologically, in 66 of 74 patients (89%) superior to penicillin -51 of 69 (74%) and 46 of 69 (67%)--administered three times a day in patients of two to 12 years of age. In Study 2, the patients enrolled were 13 years of age and older, and cefprozil administered at 20 mg/kg once a day had similar clinical (93% vs. 90%) and bacteriological (95% vs. 94%) response rates as cefaclor administered three times a day. Study 3 demonstrated that cefprozil administered twice daily was similar to penicillin given three times a day, the clinical satisfactory response being 164 of 175 (94%) for cefprozil and 146 of 165 (88%) for penicillin. In Study 4, identical clinical and bacteriologic responses (95%) were observed for cefprozil administered once a day and erythromycin ethylsuccinate administered four times a day in children over two years of age. There were no significant differences in the incidence or severity of drug-related adverse events, which, when reported, were mild and transient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Respiratory epithelial cell expression of human transforming growth factor-alpha induces lung fibrosis in transgenic mice.

Increased production of EGF or TGF-alpha by the respiratory epithelial cells has been associated with the pathogenesis of various forms of lung injury. Growth factors and cytokines are thought to act locally, via paracrine and autocrine mechanisms, to stimulate cell proliferation and matrix deposition by interstitial lung cells resulting in pulmonary fibrosis. To test whether TGF-alpha mediates pulmonary fibrotic responses, we have generated transgenic mice expressing human TGF-alpha under control of regulatory regions of the human surfactant protein C (SP-C) gene. Human TGF-alpha mRNA was expressed in pulmonary epithelial cells in the lungs of the transgenic mice. Adult mice bearing the SP-C-TGF-alpha transgene developed severe pulmonary fibrosis. Fibrotic lesions were observed in peribronchial, peribronchiolar, and perivascular regions, as well as subjacent to pleural surfaces. Lesions consisted of fibrous tissue that included groups of epithelial cells expressing endogenous SP-C mRNA, consistent with their identification as distal respiratory epithelial cells. Peripheral fibrotic regions consisted of thickened pleura associated with extensive collagen deposition. Alveolar architecture was disrupted in the transgenic mice with loss of alveoli in the lung parenchyma. Pulmonary epithelial cell expression of TGF-alpha in transgenic mice disrupts alveolar morphogenesis and produces fibrotic lesions mediated by paracrine signaling between respiratory epithelial and interstitial cells of the lung.

Animals↗

Expression of vascular cell adhesion molecule-1 in kidney allograft rejection.

VCAM-1, a leukocyte adhesion molecule expressed by cytokine-activated endothelial cells in culture, may mediate mononuclear leukocyte infiltration in vessels and interstitium in solid organ allograft rejection. Using the avidin-biotin immunoperoxidase technique and an affinity-purified rabbit polyclonal antisera to recombinant human VCAM (rVCAM Ab) which works in methyl Carnoy's fixed tissues, we studied the expression of this molecule in biopsies of transplanted kidneys (N = 34) with and without features of rejection and allograft nephrectomies (N = 17) as well as nontransplanted control tissues (N = 26). The rVCAM Ab showed a population of reactive endothelial cells limited to sites of prominent subendothelial leukocytic cell infiltration in arteries and veins, and occasional peritubular capillaries (PTC) in rejecting allografts. Endothelial expression of VCAM was rarely identified in biopsies showing interstitial rejection only or cyclosporine toxicity, usually in PTC, and was only rarely encountered in nontransplanted control tissues. Apparent de novo expression of VCAM-1 by arterial smooth muscle cells and mesangial cells was present in cases of severe rejection. In addition, a population of cells (DC) with dendritic morphology was identified by rVCAM Ab within sites of lymphoid cell aggregation in rejecting allografts. Further evidence that these cells represent true DC was obtained by identification of VCAM-1 positive, morphologically similar cells in both germinal centers and interfollicular areas of all seven reactive lymph nodes tested; and by similar staining of these cells in the allografts and lymph nodes by antibodies to nerve growth factor receptor and the complement receptor CR1, previously shown to recognize DC. DCs were generally not seen in uninflamed normal control organs or portions of allografts uninvolved by lymphoid aggregates. Enhanced tubular epithelial cell expression of VCAM-1 was also present in rejecting allografts. All staining could be abolished by absorption of the antisera with VCAM-1 transfected, but not ICAM-1 or ELAM-1 transfected, CHO cells. In situ hybridization studies utilizing a cDNA probe to human VCAM-1 demonstrated mRNA production by glomerular, tubular and vascular cells corresponding to sites where the protein was immunohistochemically localized.(ABSTRACT TRUNCATED AT 400 WORDS)

Arteries↗

Comparative safety and efficacy of clarithromycin and amoxicillin/clavulanate in the treatment of acute otitis media in children.

Clarithromycin is a new macrolide antibiotic with a wide spectrum of activity that includes the pathogens commonly causing pediatric otitis media. This randomized, investigator-blinded, multicenter trial compared the safety and efficacy of clarithromycin and amoxicillin/clavulanate in the treatment of acute otitis media in patients ages 6 months to 12 years. A total of 338 patients with acute otitis media diagnosed by otoscopy were randomized to receive clarithromycin 7.5 mg/kg twice daily, maximum 500 mg twice daily (n = 161), or amoxicillin/clavulanate 13.3 mg/kg three times daily, maximum 500 mg three times daily (n = 177), for 10 days. Treatment groups were comparable with respect to demographics, severity of infection and number of previous episodes. Efficacy was assessed by clinical examination performed within 48 hours of finishing study medication. A successful clinical response was seen in 90% (121 of 135) of evaluable clarithromycin patients vs. 92% (133 of 145) of evaluable amoxicillin/clavulanate patients (P = 0.681). Clinical failure or relapse (Posttreatment Days 0 to 4) occurred in 10% (14 of 135) of clarithromycin-treated patients vs. 8% (12 of 145) of amoxicillin/clavulanate-treated patients. Gastrointestinal adverse events were the most commonly reported in both groups. Of these events diarrhea was the most frequent, occurring in 12% (19 of 161) of clarithromycin and 32% (57 of 177) of amoxicillin/clavulanate-treated patients (P < 0.001). These results indicate that the efficacy of clarithromycin oral suspension was comparable with amoxicillin/clavulanate oral suspension in the treatment of acute otitis media in children. Clarithromycin was better tolerated than amoxicillin/clavulanate with a lower incidence of gastrointestinal side effects.

Acute Disease↗

Treatment of pharyngitis and tonsillitis with cefprozil: review of three multicenter trials.

Cefprozil is a new oral cephalosporin with an in vitro spectrum of activity that includes group A beta-hemolytic streptococci (Streptococcus pyogenes). Three multicenter, randomized trials were conducted for comparing the clinical efficacy and safety of cefprozil administered once or twice daily with that of cefaclor, penicillin, or erythromycin ethylsuccinate administered three or four times daily in the treatment of mild-to-moderate tonsillopharyngitis. In the cefprozil-cefaclor trial, the pathogen eradication rate for evaluable patients receiving cefprozil was 83%, which was significantly better than that for patients receiving cefaclor (76%) (P = .035). The rate of satisfactory clinical response was similar with cefprozil (89%) and cefaclor (84%). The overall response rate was significantly better with cefprozil (80%) than with cefaclor (72%, P = .018). Differences in response rates were not noted when analyzing only patients 2-12 years of age. In the cefprozil-penicillin trial, the eradication rate of bacteriologic pathogens was similar in patients receiving cefprozil (91%) and in patients receiving penicillin (87%). A satisfactory clinical response was seen in 95% of the evaluable cefprozil-treated patients, which was significantly better than the rate of satisfactory clinical response seen in the penicillin-treated patients (88%; P = .023). In addition, during-therapy cultures for penicillin-treated patients yielded a significantly higher rate of beta-lactamase-producing Staphylococcus aureus than did those for the group of cefprozil-treated patients (13% vs. 4.5%, respectively; P = .046). Significantly more clinically symptomatic bacteriologic failures occurred in the penicillin group (P = .037).(ABSTRACT TRUNCATED AT 250 WORDS)

Cefaclor↗