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Pityriasis lichenoides in childhood: a retrospective review of 124 patients.

BACKGROUND: Pityriasis lichenoides (PL) occurs in all age groups, although predominantly in younger individuals. OBJECTIVE: We sought to study the clinical features of PL in children followed up at our institution. METHODS: The records of 124 children who were given the diagnosis of PL at our institution between 1993 and 2003 were retrospectively reviewed. RESULTS: PL chronica (PLC) was recorded in 37% of the cases, PL et varioliformis acuta (PLEVA) in 57.3%, and clinical features of both disorders were seen simultaneously in the remaining. The median age of onset was 60 months (range: 6-180 months), although the median age of onset of PLEVA (median: 60 months) was significantly younger than that of PLC (median: 72 months) (P = .03). The age distribution showed peaks at 2 to 3 years (24.8%) and 5 to 7 years (32%). A history of infection or drug intake preceded the skin manifestations in 30% and 11.2% of patients with PLC and PLEVA, respectively. The disease began most commonly during winter (35%) or fall (30%). The median duration was 20 months (range: 3-132 months) in patients with PLC and 18 months (range: 4-108 months) in patients with PLEVA. Involvement was diffuse in 74.2% of the patients, peripheral in 20.2%, and central in the remainder. The disease was recurrent in 77% of the patients (n = 80). Of the patients, 59% had pruritus, whereas 32% reported no symptoms; the remainder had fever, arthralgia, or both. Erythromycin estolate or ethylsuccinate was administered to 79.7% of the affected children; 66.6% of these showed at least a partial response. LIMITATIONS: The analyzed data were collected retrospectively and biopsies were not performed in all patients. CONCLUSIONS: PL is not an uncommon disease in childhood, with age peaks in the preschool and early school-age years. It is usually recurrent, and shows a seasonal variation with onset most often in the fall or winter. In childhood PL, erythromycin is an effective initial treatment choice.

Adolescent↗

Hepatic safety of erythromycin acistrate in 1549 patients with respiratory tract or skin infections.

Erythromycin acistrate is a new 2'-acetyl esther prodrug of erythromycin, whose structure resembles that of erythromycin estolate. However, in toxicological studies, it does not have the problems of hepatotoxicity. To assess its effects on hepatic functions in clinical practice, the liver parameters of patients with respiratory tract or skin infections were monitored during therapy. In total 1549 patients were treated for 7-14 days. In addition, 127 patients with suspected viral infections served as controls. There were no significant differences in serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyltransferase (gamma-GT) or alkaline phosphatase (APHOS) values between the erythromycin acistrate or control groups at the beginning or end of therapy. ASAT values increased moderately in 2.4% and clearly in 0.3% of patients treated, but also decreased in 2.0%. ALAT values were moderately increased in 9.9%, clearly increased in 0.6% and normalized in 3.5% of the patients. gamma-GT values increased moderately in 3.5% and and clearly in 0.3%, but decreased to normal in 3.3% of the patients. APHOS was moderately elevated in 1.0% of the patients and normalized in 1.3%. The correlation of changes between the different liver enzymes was poor. Only ten patients (0.6%) had two or more clearly elevated liver enzyme values by the end of the therapy, of whom five had increased liver enzyme activities before the treatment, two had underlying disease explaining the changes and in only three patients out of 1549 (0.2%) could hepatic changes be attributed to erythromycin acistrate therapy. These changes were reversible. The results demonstrate the hepatic safety of erythromycin acistrate in clinical practice. Concomitant food intake did not affect the safety profile.

Adolescent↗

Randomized, double blind comparison of brand and generic antibiotic suspensions: I. A study of taste in adults.

BACKGROUND: A belief that brand oral liquid medications taste better than their generic counterparts may influence prescribing habits among pediatricians. METHODS: We undertook a prospective, randomized, double blinded, comparative evaluation of the taste of brand and generic erythromycin ethylsuccinate, cephalexin monohydrate, erythromycin ethylsuccinate/sulfisoxazole, penicillin V potassium and trimethoprim-sulfamethoxazole in 42 adult volunteers. Subjects tasted one class of brand and generic antibiotics and rated them according to smell, texture, taste and aftertaste. RESULTS: At least one generic preparation of cephalexin, erythromycin ethylsuccinate/sulfisoxazole and penicillin V potassium was rated equal in taste to the respective brand name products. However, brand erythromycin estolate and trimethoprim-sulfamethoxazole name brand suspensions rated significantly higher than the other products tested. CONCLUSIONS: Based on our results brand name oral antibiotic formulations do not necessarily taste better than their generic counterparts.

Administration, Oral↗

Treatment of Group A streptococcal pharyngitis in children. Results of a prospective, randomized study of four antimicrobial agents.

Penicillin V, benzathine/procaine penicillin G, cefadroxil monohydrate, and erythromycin estolate were randomly assigned for therapy of group A streptococcal pharyngitis in 198 children. All patients improved with in 24 hours of initiating therapy. Reinfection with a new group A streptococcal serotype occurred in 13 patients, 12 developing 7 to 12 days after stopping therapy and 11 becoming symptomatic. Relapse with the same organism occurred in 16 patients, only 5 (31%) of whom were symptomatic. Antibody titer rises, antibiotic resistance of group A organisms, presence of penicillinase-producing staphylococci, and lack of compliance were not related to recurrent infections. There were no significant differences between the failure rates of the four test drugs: penicillin V, 12%; benzathine/procaine penicillin G, 12%; cefadroxil monohydrate, 5%; and erythromycin, 2%.

Adolescent↗

Intravenous amodiaquine and oral amodiaquine/erythromycin in the treatment of chloroquine-resistant falciparum malaria.

In eastern Thailand, 14 adults with moderately severe falciparum malaria were treated with intravenous amodiaquine dihydrochloride, loading dose 10 mg base/kg infused over 4 h followed by three further intravenous infusions of 5 mg base/kg at 24, 48, and 72 h. All patients were clinically cured--mean fever clearance time 37.8 h (range 24-60), mean parasite clearance time 64.9 h (18-164). There were no serious toxic effects. 33 patients aged over 5 years with uncomplicated falciparum malaria were given oral amodiaquine dihydrochloride (mean total dose 41 mg base/kg over 3 days) combined with erythromycin estolate (mean dose 48 mg base/kg daily for 5 days). 2 patients failed to respond. In the other 31 patients mean fever clearance time was 55.9 h (range 10-104) and mean parasite clearance time was 65.4 h (40-120). In both studies, more than half the patients followed-up had recurrent parasitaemia but reinfection could not be excluded. Parasites isolated from 18 patients were highly resistant to chloroquine in vitro.

Administration, Oral↗

Safety and efficacy of azithromycin in the treatment of community-acquired pneumonia in children.

OBJECTIVE: To compare the safety and efficacy of azithromycin with amoxicillin/clavulanate or erythromycin for the treatment of community-acquired pneumonia, including atypical pneumonia caused by Mycoplasma pneumoniae and Chlamydia pneumoniae. METHODS: Multicenter, parallel group, double blind trial in which patients 6 months to 16 years of age with community-acquired pneumonia were randomized 2:1 to receive either azithromycin for 5 days or conventional therapy for 10 days (amoxicillin/clavulanate if < or =5 years of age or erythromycin estolate if >5 years of age). Patients from 23 geographically diverse sites were evaluated for clinical outcomes and/or adverse events at Days 3 to 5, Days 15 to 19 and 4 to 6 weeks posttherapy. Microbiology (culture or polymerase chain reaction) was done at baseline and Days 15 to 19 for bacteria, Chlamydia pneumoniae and Mycoplasma pneumoniae. Serology for C. pneumoniae and M. pneumoniae was done at baseline and 4 to 6 weeks posttherapy. RESULTS: Of 456 patients enrolled during 17 consecutive months, 420 were evaluable. Clinical success at Study Days 15 to 19 was 94.6% in the azithromycin group and 96.2% in the comparative treatment group (P = 0.735) and at 4 to 6 weeks posttherapy 90.6 and 87.1%, respectively (P = 0.330). Evidence of infection was identified in 46% of 420 evaluable patients (1.9% bacteria, 29.5% M. pneumoniae and 15% C. pneumoniae). Microbiologic eradication was 81% for C. pneumoniae and 100% for M. pneumoniae in the azithromycin group vs. 100 and 57%, respectively, in the comparator group. Treatment-related adverse events occurred in 11.3% of the azithromycin group and 31% in the comparator group (P < 0.05). CONCLUSION: Azithromycin used once daily for 5 days produced a satisfactory therapeutic outcome similar to those of amoxicillin/clavulanate or erythromycin given three times a day for 10 days for treatment of community-acquired pneumonia. Azithromycin had significantly fewer side effects than comparator drugs.

Adolescent↗

[Importance of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired pneumonia].

OBJECTIVES: To determine the importance of Mycoplasma pneumoniae and Chlamydia pneumoniae in community-acquired pneumonia (CAP) of children from different latitudes and to compare clinical outcome using azithromycin (AZM) versus either amoxicillin-clavulanate (A-C) or erythromycin estolate (EE). METHODS: Ambulatory patients with CAP were identified at either the Children's Medical Center of Dallas, Texas or the Hospital del Niño of Panama City, Panama. Children 6 months to 15 years of age were enrolled and randomized to receive either AZM for 5 days or a 10 day course of either A-C or EE, for those younger or older than 5 years of age, respectively. Mycoplasma pneumoniae and C. pneumoniae were identified by measuring acute and convalescent serum antibody titers and by performing nasopharyngeal (NP) and oropharyngeal (OP) swabs for culture and polymerase chain reaction (PCR) testing. RESULTS: Overall 335 patients (168 in Dallas and 167 in Panama) were evaluated from February 1996 through December 1997. Acute M. pneumoniae infection was detected in 12 (7%) patients each in Dallas and Panama. Acute C. pneumoniae infection was observed in 10 (6%) children at each site. Infection caused by these "atypical" microorganisms occurred more frequently in children older than 5 years of age (23% vs 9%, P = 0.001, RR 2.5, 95% CI 1.4-4.3). No distinctive pattern of clinical or radiologic abnormalities was seen in relation to etiology. Clinical cure was achieved in 43 of 44 children infected by these bacteria regardless of treatment assignment. CONCLUSION: Mycoplasma pneumoniae and C. pneumoniae are common etiologic agents of CAP in older children from different latitudes. Children with CAP present with similar clinical and radiologic findings to those caused by other etiologic agents. Outcome was excellent for the three treatment regimens studied.

Adolescent↗

A comparison of the in-vitro activity of some 5-nitroimidazoles and other compounds against Giardia intestinalis.

The activities of 11 5-nitroimidazole compounds have been compared against Giardia intestinalis in vitro using a 3H-thymidine incorporation assay. All the compounds were at least equipotent to, or more active than metronidazole with the exception of panidazole. Satranidazole, ronidazole and S75 0400 A were all about five times more active than metronidazole and warrant further study as potential chemotherapeutic agents for man. No major differences in the response to these compounds was found between two stocks of Giard. intestinalis with the exception of flunidazole. Several other antiprotozoal drugs showed activity against Giard. intestinalis. Berberine sulphate, paromomycin sulphate, erythromycin estolate and sulphasalazine, all of which have been used to treat human patients, showed no activity in vitro.

Giardia↗

Use of a low-density microarray for studying gene expression patterns induced by hepatotoxicants on primary cultures of rat hepatocytes.

In the field of gene expression analysis, DNA microarray technology is having a major impact on many different areas including toxicology. For instance, a number of studies have shown that transcription profiling can generate the information needed to assign a compound to a mode-of-action class. In this study, we investigated whether compounds inducing similar toxicological endpoints produce similar changes in gene expression. In vitro primary rat hepatocytes were exposed to 11 different hepatotoxicants: acetaminophen, amiodarone, clofibrate, erythromycin estolate, isoniazid, alpha-naphtylylisothiocyanate, beta-naphtoflavone, 4-pentenoic acid, phenobarbital, tetracycline, and zileuton. These molecules were selected on the basis of their variety of hepatocellular effects observed such as necrosis, cholestasis, steatosis, and induction of CYP P450 enzymes. We used a low-density DNA microarray containing 59 genes chosen as relevant toxic and metabolic markers. The in vitro gene expression data generated in this study were generally in good agreement with the literature, which mainly concerns in vivo data. Furthermore, gene expression profiles observed in this study have been confirmed for several genes by real-time PCR assays. All the tested drugs generated a specific gene expression profile. Our results show that even with a relatively limited gene set, gene expression profiling allows a certain degree of classification of compounds with similar hepatocellular toxicities such as cholestasis, necrosis. The clustering analysis revealed that the compounds known to cause steatosis were linked, suggesting that they functionally regulate similar genes and possibly act through the same mechanisms of action. On the other hand, the drugs inducing necrosis and cholestasis were pooled in the same cluster. The drugs arbitrarily classified as the CYP450 inducers formed individual clusters. In conclusion, this study suggests that low-density microarrays could be useful in toxicological studies.

Animals↗

Evaluation of hepatotoxic potential of drugs by inhibition of bile-acid transport in cultured primary human hepatocytes and intact rats.

Inhibition of canalicular bile acid efflux by medications is associated with clinical liver toxicity, sometimes in the absence of major liver effects in experimental species. To predict the hepatotoxic potential of compounds in vitro and in vivo, we investigated the effect of clinical cholestatic agents on [3H]taurocholic acid transport in regular and collagen-sandwich cultured human hepatocytes. Hepatocytes established a well-developed canalicular network with bile acid accumulating in the canalicular lumen within 15 min of addition to cells. Removing Ca2+ and Mg2+ from the incubation buffer destroyed canalicular junctions, resulting in bile acid efflux into the incubation buffer. Canalicular transport was calculated based on the difference between the amount of bile acid effluxed into the Ca/Mg2+-free and regular buffers with linear efflux up to 10 min. Hepatocytes cultured in the nonsandwich configuration also transported taurocholic acid, but at 50% the rate in sandwiched cultures. Cyclosporin A, bosentan, CI-1034, glyburide, erythromycin estolate, and troleandomycin inhibited efflux in a concentration-dependent manner. In contrast, new generation macrolide antibiotics with lower incidence of clinical hepatotoxicity were much less potent inhibitors of efflux. An in vivo study was conducted whereby glyburide or CI-1034, administered iv to male rats, produced a 2.4-fold increase in rat total serum bile acids. A synergistic 6.8-fold increase in serum total bile acids was found when both drugs were delivered together. These results provide methods to evaluate inhibitory effects of potentially cholestatic compounds on bile-acid transport, and to rank compounds according to their hepatotoxic potential.

Animals↗

Compliance of German pediatric patients with oral antibiotic therapy: results of a nationwide survey.

BACKGROUND: Noncompliance with a prescribed therapy is a common problem in ambulatory pediatrics. OBJECTIVE: To establish a nationwide status quo of compliance of German ambulatory pediatric patients with oral antibiotics prescribed for various bacterial infections. PATIENTS AND METHODS: In this study, organized and financed by the German Society for Pediatric Infectious Diseases, 42 pediatricians in private practice who were selected to represent the 3 main regions of Germany and residence in large cities or small towns, respectively, enrolled consecutive patients who had bacterial infections that required therapy with oral antibiotics. Choice of agent and duration of treatment were left to the study physicians. Compliance was measured by a standardized telephone interview on the penultimate day and a urine bioassay for antibacterial activity on the last day of the planned treatment period. Parents did not know the true purpose of the study. RESULTS: Five hundred eight-four patients were fully evaluable. The most frequent diagnoses included tonsillopharyngitis (n = 231), otitis media (n = 170) and lower respiratory tract infections (n = 114). Most frequently prescribed antibiotics included amoxicillin (n = 102), potassium penicillin V (n = 81) and clarithromycin (n = 67). Overall compliance (positive urine test) on the last day of therapy was 69.5% (406 of 584 patients). Compliance was not significantly influenced by the region of residence or the underlying bacterial infection. It was significantly associated with the antibiotic used (macrolides, 89.0%; penicillins, 62.2%; cephalosporins, 66.4%; P = 0.0001 for macrolides vs. the others). Best compliance was found with clarithromycin (94.0%) and erythromycin estolate (89.8%). Compliance was also significantly better in patients > or =6 years old (77.7%; P = 0.016); with a treatment duration of < or =7 days (77.6%; P = 0.014); when the drug package contained a dose-taking reminder (79.7%; P = 0.003); and when the pediatrician's behavior toward the patient was assessed by the parents as "very sympathetic" or "sympathetic" (72.6%; P = 0.017). Subjecting all variables to logistic regression analysis, we found 3 variables to be significant predictors of treatment compliance: choice of antibiotic (P = 0.0001); patient age (P = 0.0008); and residence in town or city (P = 0.03). CONCLUSIONS: A noncompliance rate of >30% is unsatisfactory. Whereas some variables significantly associated with compliance cannot be influenced (patient age; place of residence in town or city), others are amenable to modifications. These include the physician-patient interaction and the choice of antibiotic. Agents should be preferred that are well-accepted by patients, that enable short-term therapy with few daily doses and with a package that contains a dose-taking reminder.

Administration, Oral↗

X-ray powder diffraction patterns for certain beta-lactam, tetracycline and macrolide antibiotic drugs.

X-ray powder diffraction (XRD) data for eight beta-lactam viz., ampicillin sodium, ampicillin trihydrate, penicillin G procaine, benzathine penicillin, benzyl penicillin sodium, cefalexin, cefotaxime sodium and ceftriaxone sodium; three tetracyclines viz., doxycycline hydrochloride, oxytetracycline dihydrate and tetracycline hydrochloride; and two macrolide viz., azithromycin and erythromycin estolate antibiotic drugs were obtained using a powder diffractometer. The drugs were scanned from Bragg angles (2theta) of 10 degrees to 70 degrees. The obtained data were tabulated in terms of the lattice spacing (A) and relative line intensities (I/I(I)). This new information may be useful for identifying these drugs from confiscated materials, which has been frequently encountered in forensic laboratories.

Anti-Bacterial Agents↗

[Risks of antibacterial agents in pregnancy].

Antimicrobial therapy in the pregnant woman has to consider the potential risks of antibacterial agents for the developing foetus and the mother. Extensive clinical experience shows that penicillins, cephalosporins and erythromycin (except erythromycin estolate) can be considered safe for the developing foetus and for the pregnant woman. Nitrofurantoin is a valid antibacterial option in pregnancy, except in the latter stages. Isoniazid and ethambutol are the safest drugs for the treatment of tuberculosis in pregnancy, but attention must be paid to the potential toxicity of isoniazid for the mother. For several other antimicrobial agents (aminoglycosides, fluoroquinolones, newer macrolides, metronidazole, rifampicin, vancomycin) a potential teratogenic or toxic risk has been documented in animal or human studies: however, their use during pregnancy is justified when there is no safer alternative. A few antibacterials should be absolutely avoided in pregnancy: tetracyclines, cotrimoxazole and chloramphenicol according to a teratogenic risk or a toxic risk for the foetus or the mother, and clindamycin according to its high risk/benefits ratio. The safety data in pregnancy of many other antibacterials, including carbapenems, ketolides and streptogramines, are very limited or lacking. More data on the risks of antibacterial agents are needed for an optimal therapy of bacterial infections in pregnancy.

Anti-Bacterial Agents↗

Surgical management of Rhodococcus equi metaphysitis in a foal.

A chronic Rhodococcus equi metaphysitis involving the distal growth plate of the left third metatarsal bone had induced a longstanding lameness in a young foal. Abnormal hematologic values included mild anemia, hyperfibrinogemia, mild leukocytosis, and neutrophilia. Radiography of the distal portion of MT3 revealed a radiolucent zone on the medial aspect of the growth plate, and small pieces of bone suggestive of sequestra. Treatment with erythromycin estolate and rifampin, aggressive surgical debridement, and cancellous bone grafting helped resolve the bone infection.

Abscess↗

Considerations of antibiotic therapy during pregnancy.

The use of antibiotics in pregnancy requires that the clinician consider both toxicity to and pharmacokinetics for mother and fetus. Although most adverse reactions to antibiotics in the adult are not modified by pregnancy, those to tetracycline and erythromycin estolate are the exceptions. Tetracycline is contraindicated throughout pregnancy because of fetal effects, whereas sulfa preparations, trimethoprim, and chloramphenicol are contraindicated only at specific times during gestation. The pharmacokinetics of antibiotics in the mother are such that lower serum concentrations are achieved for a given dose, which may be important in serious or resistant infections. Fetal kinetics are such that transfer to amniotic fluid and distribution within the fetus may not provide adequate protection for the fetus in cases of chorioamnionitis.

Abnormalities, Drug-Induced↗

Drug interferences with tests performed by a 12-channel autoanalyzer.

The information reported in a variety of sources on drug interferences with routine laboratory tests (serum concentrations of sodim, potassium, carbon dioxide, chloride, glucose, BUN, cholesterol, total protein, albumin, total bilirubin, alkaline phosphatase, and SGOT) performed by a 12-channal autoanalyzer was reviewed. A determination was made whether or not the information was based on an evaluation of original articles, if the study was done in vitro or in vivo, what medium was used, if the drug level causing the interference would be encountered in a patient's serum, and if the reported conclusions were clinically significant. The review narrowed considerably the list of drug interactions with laboratory tests performed by 12-channel autoanalyzer methods. Clinically significant interactions were found for (1) aminosalicylic acid and the test for serum glucose; (2) gamma globulins and cholesterol measurement; (3) sulfonamides and paramethadione and the test for albumin; (4) albumin from placental sources and alkaline phosphatas measurement; (5) erythromycin estolate and aminosalicylic acid and the determination of SGOT; and, possibly (5) medications releasing bromide ions and the measurement of serum chloride. The study showed the need to determine the relevancy of drug interactions to the specific methods used in the laboratory of each medical institution.

Autoanalysis↗