Informe diário de evidências COVID-19: busca realizada em 20 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 20, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos.

Pertussis Accompanying Recent Mycoplasma Infection in a 10-Year-Old Girl / 감염과화학요법

Recently, the incidence of pertussis has been increasing; however, reports on mixed infection of pertussis with other respiratory pathogens are rare in highly immunized populations. We report the case of a 10-year-old girl who presented with cough, post-tussive emesis, and fever. She was subsequently diagnosed with bronchopneumonia. Although she had received five doses of diphtheria-tetanus-acellular pertussis vaccine, polymerase chain reaction of her nasopharyngeal aspirate confirmed Bordetella pertussis infection. In addition, serologic testing for Mycoplasma pneumoniae was also positive. The patient was treated with roxithromycin without any complications. This is the first report of mixed B. pertussis and M. pneumoniae infection in Korea. To avoid under-diagnosis, pertussis should be considered in patients with chronic cough even when other respiratory pathogens have been documented.

Bronchiolitis Obliterans Associated with Stevens-Johnson Syndrome: A Case Report

We report a case of bronchiolitis obliterans associated with Stevens-Johnson syndrome. A 59-year-old man presented with respiratory distress that gradually worsened over 3 months. He had been diagnosed with Stevens-Johnson syndrome 3 months before admission. He had no history of previous airway disease. On physical examination, expiratory breathing sounds were not audible, and a chest X-ray revealed a hyperinflated lung. A pulmonary function test indicated a severe obstructive pattern. Computed tomography scans of inspiratory and expiratory phases of respiration showed oligemia and air trapping, and both were more prominent on expiration view than on inspiration view. The pathogenesis of bronchiolitis obliterans associated with Stevens-Johnson syndrome is largely unknown.

Infecciones de transmisión sexual por Ureaplasma urealyticum y Mycoplasma hominis / Sexually-transmitted infections in Ureaplasma urealyticum and Mycoplasma hominis

Ureaplasma urealyticum y Mycoplasma hominis son bacterias anaerobias facultativas, que se asocian con la colonización e infección genital en los seres humanos adultos, aunque también pueden aislarse en individuos asintomáticos, lo que sugiere que pueden comportarse como patógenos oportunistas. El objetivo de este trabajo consistió en determinar la prevalencia de estos microorganismos en pacientes consultantes al Servicio de Enfermedades de Transmisión Sexual y Sida del Instituto Nacional de Epidemiología de la ciudad de Mar del Plata. Se realizó un estudio epidemiológico de tipo retrospectivo de 312 muestras de pacientes adultos de ambos sexos consultantes entre los años 2001 y 2006. La distribución por sexos fue 67.3% mujeres y 32.7% hombres, con edades comprendidas entre 15 y 71 años. La prevalencia de infección por Ureaplasma urealyticum fue de 51.9 % y la de Mycoplasma hominis de 25.6 %. La detección de estos microorganismos en forma simultánea para un mismo paciente fue de 30.2 %. La doxiciclina fue el antibiótico que mayor sensibilidad presentó frente a estos aislamientos. Candida albicans resultó el microorganismo más asociado a la presencia concomitante de U. urealyticum y M. hominis. De acuerdo con los datos obtenidos resulta necesario intensificar la detección de estos microorganismos potencialmente patógenos para monitorear su circulación en la población...

Detection and the antibiotic susceptibility analysis of mycoplasma and chlamydia in urogenital tract infections of 327 cases patients with tubal infertility / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the effects of mycoplasma and chlamydia infections on tubal infertilityand to assess the antibiotic susceptibility and resistance of female urogenital, and consequently to guide clinical rational drug use.</p><p><b>METHODS</b>327 tubal infertility women as infertility group and 286 healthy pregnant women as control group were randomly selected, detected chlamydia trachomatis (CT), ureaplasma urealyticum (UU) and mycoplasma hominis (MH) in cervical secretions and drug resistance of UU and MH.</p><p><b>RESULTS</b>CT infection rates (14.99%), UU infection rates (23.24%), UU + MH infection rates (29.05%),CT + UU + MH infection rates (9.17%) and total infection rates (88.99%) in infertility group is higher than those (order: 2.80%, 6.99%, 8.39%, 4.55%, 29.02%) in the control group, comparisons of two groups are statistically significant differences (P < 0.05), the susceptibility of UU to roxithromycin (sensitivity is 96.05%), josamycin (sensitivity is 96.05%), tetracycline (sensitivity is 82.89%), vibramycin( sensitivity is 92.11%) and clarithromycin (sensitivity is 96.05%) were relatively high and low to ciprofloxacin and acetyl spiramycin. The susceptibility of MH to josamycin (sensitivity is 95.83%), vibramycin (sensitivity is 91.67%), minocin (sensitivity is 83.33%) and actinospectacin (sensitivity is 75.00%) were relatively high and low to erythromycin, azithromycin, roxithromycin and clarithromycin. UU + MH was only sensitive to josamycin (sensitivity is 90.52%), high resistance (77.89% -91.58%) to erythromycin, azithromycin, acetyl spiramycin, ciprofloxacin, ofloxacin, azithromycin and clarithromycin.</p><p><b>CONCLUSION</b>Infection of CT, UU, MH and tubal infertility have certain relevance,the rates of CT, UU and MH infection in tubal infertility patients higher than fertile people. For many commonantibacterial drugs, UU, MH and UU + MH has strong resistance, the etiology detection and using adapted antibios should be taken seriously in clinical treatment.</p>

An empirical study of treating chronic sinusitis with low dose Roxithromycin / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#Observe the therapeutic effect of low dose Roxithromycin in treating chronic sinusitis and further discuss the mechanism of Roxithromycin facile endothelial cell apoptosis.@*METHOD@#All 47 patients who suffer chronic sinusitis at out-patient clinic from 2006. 10 to 2008. 03 were administered low dose Roxithromycin. Follow up all the patients and get polypi at 3-month and 6-month. AO/EB was employed to detect the apoptosis of endothelial cell.@*RESULT@#At 3-month and 6-month the improvement of ventilation are 37.25 +/- 12.21, 63.15 +/- 22.78; Decrease of nasal discharge are 42.12 +/- 13.56, 74.45 +/- 28.79; alleviation of headache are 18.98 +/- 7. 66, 34.47 +/- 14.11; Improvement of olfactory are 21.23 +/- 8.41, 38.18 +/- 16.54; Apoptotic index are (39.54 +/- 6.86)% and (62.34 +/- 8.67)%, which are significantly different (P<0.05).@*CONCLUSION@#Low dose Roxithromycin has good long term curative effect in treating chronic sinusitis. Low dose Roxithromycin can greatly urge the apoptosis of endothelial cell.

Pharmacokinetics and relative bioavailability study of roxithromycin tablet in Chinese healthy volunteers by LC-MS/MS / 生物医学工程学杂志

This is a study of assessing the comparative bioavailability of roxithromycin produced by two companies in 36 healthy volunteers. On the basis of informed consent, 36 healthy male volunteers received each medicine at the roxithromycin dose of 150mg in a cross-over study. There was a 1-week washout period among the doses. Plasma concentrations of roxithromycin were monitored by an LC-MS/MS for over a period of 72 hours after administration. In this study, roxithromycin was generally well tolerated. After an oral administration of roxithromycin capsule, the pharmacokinetic parameters of roxithromycin, such as AUC(0-72 h) (66 076 microg x L x h(-1) and 70 334 microg x L x h(-1) for test and reference capsule, respectively) and AUC(0-infinity) (68 153 microg x L x h(-1) and 72 362 microg x L x h(-1)) were significantly similar. For test and reference capsule, the values of C(max) were 6 631.5 microg x L(-1) and 7 033.9 microg x L(-1) respectively, of T1/2 were 15.39 +/- 4.61 h and 16.06 +/- 5.56 h, and of T(max) were 1.3 +/- 0.9 h and 1.4 +/- 0.7 h respectively. The relative bioavailability F was 94.9% +/- 22.4% of tested formulation. The values of 90% confidence interval around the ratios (test/reference) (obtained by analysis of variance, ANOVA) were 88.3%-101.2% for C(max), 86.2%-98.9% for AUC(0-72) h, being within the predefined acceptable range for the conclusion of bioequivalence. The results of statistical analysis suggest that the two formulations be bioequivalent.

Roxithromycin Suppresses MUC5B/8 Mucin Genes and Mucin Production in Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Macrolide antibiotics are known to inhibit mucus hypersecretion in patients with chronic airway diseases, but its action mechanism is unclear. Several reports demonstrated that macrolides significantly inhibited gene expression of MUC2, MUC4 and MUC5AC in the airway epithelial cells, but little is known about its inhibitory effect for the other important airway mucins. In upper airway tracts, MUC5B and MUC8 are other important secreted mucin genes. Therefore, this study was aimed to investigate the effects of roxithromycin on the IL-1beta-induced gene expression and mucin production of MUC5B and MUC8 in NCI-H292 cells and cultured human nasal polyp epithelial cells. SUBJECTS AND METHOD: The effects of roxithromycin on the IL-1beta-induced MUC5B and MUC8 expression were analyzed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Roxithromycin attenuated the IL-1beta-induced MUC5B and MUC8 gene expression and mucin production with a dose-dependent pattern in NCI-H292 epithelial cells and cultured human nasal polyp epithelial cells. CONCLUSION: Roxithromycin exerts direct inhibitory effects on the gene expression of MUC5B and MUC8 in airway epithelial cells. These novel findings may explain the clinical efficacy of 14-membered macrolides in the treatment of chronic airway inflammations.

Co-prescribing Patterns of Contraindicated Drugs for the Elderly Patients in Busan / 한국역학회지

PURPOSE: To estimate the prevalence of co-prescribing contraindicated drugs for elderly patients in Busan. METHODS: We used the Health Insurance Review Agency (HIRA) claims database. Study population consisted of elderly patients who visited clinics or hospitals in Busan metropolitan city from January 1, 2000 to December 31, 2001. Contraindicated drugs were defined as 162 combinations of contraindicated drugs announced by the Korea Ministry of Health and Welfare in 2004. The co-prescription of contraindicated drugs was defined as prescribing two or more contraindicated drugs in combination in the same prescription. The prevalence of co-prescribing contraindicated drugswas estimated as proportion of co-prescribed patients out of the study patients. We estimated and age-adjusted prevalence and its 95% confidence interval of co-prescription of contraindicated drugs among the elderly patients in Korean population in 2001. RESULTS: The study elderly patients were 262,952 with 2,483,227 prescriptions. Among the study patients 1,208 (4.6%) were prescribed contraindicated drugs in combination. A total of 16,255 patients were estimated as the number of co-prescribed patients among the Korean elderly in 2001. Age-standardized prevalence of co-prescription to the Korean elderly was estimated to be 45 per 10,000 persons. The most frequently prescribed combinations were cisapride & amitriptyline, roxithromycin & ergoloid mesylate, and terfenadine & erythromycin, and the frequency were 325 (16.8%), 149 (7.7%), and 132 (6.8%),respectively. CONCLUSIONS: The contraindicated drugs were co-prescribed to the elderly patients in Korea. Many of these co-prescriptions should be avoided if unnecessary. The patients should be carefully monitored if they were inevitably prescribed the contraindicated drugs.

Emergence of macrolide resistance and clinical use of macrolide antimicrobials in children / 소아과

Macrolide antimicrobial agents including erythromycin, roxithromycin, clarithromycin, and azithromycin are commonly used in the treatment of respiratory tract infections in children. Newer macrolides that have structural modifications of older drug erythromycin show improved change in the spectrum of activity, dosing, and administration. However, recent studies reported that increasing use of macrolide antibiotics is the main force driving the development of macrolide resistance in streptococci. In particular, azithromycin use is more likely to select for macrolide resistance with Streptococcus pneumoniae than is clarithromycin use, a possible reflection of its much longer half life. Recently, erythromycin resistance rates of S. pneumoniae and Streptococcus pyogenes are rapidly increasing in Korea. Two main mechanisms of acquired macrolide resistance have been described, altered binding site on the bacterial ribosome encoded by the ermB gene and active macrolide efflux pump encoded by the mef gene. Relationship between the susceptibility of S. pneumoniae and the response to macrolides has been shown in studies of acute otitis media, but less clear in cases of pneumonia. This article reviews the spectrum of activity, pharmacokinetic properties, mechanisms of action and resistance, and clinical implication of resistance on the treatment of respiratory tract infections in children.

Relative bioavailability of roxithromycin dispersive tablets in healthy volunteers / 生物医学工程学杂志

The relative bioavailability of roxithromycin dispersive tablet in healthy volunteers was evaluated in this study. Its concentration in plasma was detected by high performance liquid chromatography (HPLC) after twenty healthy male volunteers were given each a single dose of 300 mg roxithromycin. The experiment data were obtained using DAS programme. The values of Cmax were 10.16+/-1.46 and 10.34+/-1.66 microg x ml(-1) at 2.33+/-0.61 and 2.28+/-0.62 h respectively; of t1/2 were 9.00+/-1.58 and 8.68+/-1.66 h respectively; of AUC0-->Tn were 143.32 +/-25. 80 and 138.93+/-22. 49 microg x h x ml(-1) respectively; of AUC0-->infinity were 158.63+/-26.86 and 153.77+/-24.75 microg x h x ml(-1) for test and reference drugs. Relative bioavailability of the tested roxithromycin was 103.63%+/-14.04%. The result showed that the two dispersive tablets are bioequivalent.

Effect of Macrolide on the MUC4 Gene Expression in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mucin gene expression and mucin secretion are highly increased by inflammatory airway diseases such as asthma, chronic bronchitis and rhinosinusitis. Macrolide antibiotics is considered one of the effective drugs inhibiting mucus secretion for chronic bronchitis and rhinosinusitis with nasal polyp. However, the anti-secretory effect of macrolide is not clear. This study was designed to investigate whether macrolide can suppress interleukin-1beta (IL-1beta)-induced MUC4 gene expression and mucin secretion in the cultured human nasal polyp epithelial cells and NCI-H292 epithelial cells. SUBJECTS AND METHOD: Nasal polyps were obtained from 20 patients with chronic rhinosinusitis with nasal polyp during endoscopic sinus surgery. We observed the effect of roxithromycin on the IL-1beta-induced MUC4 gene and mucin secretion by reverse transcriptase-polymerase chain reaction (RT-PCR) with enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Roxithromycin attenuated the IL-1beta-induced MUC4 mRNA expression and mucin secretion with a dose dependent pattern in both of the cultured human nasal polyp epithelial cells and NCI-H292 epithelial cells. CONCLUSION: This result suggests that roxithromycin may be considered as an effective anti-hypersecretory agent for its down-regulation of the MUC4 gene.

A Case of Tinea Barbae Caused by Trichophyton mentagrophytes / 대한피부과학회지

We report a case of tinea barbae in a 51-year-old man, who presented with erythematous pustules on the upper lip, and a relatively well-defined pustular patch on his left cheek. Histopathologically, fungal hyphae were found in the hair shaft upon PAS staining. A fungal culture from scales and tissue of the lesions was grown on Sabouraud's dextrose agar and showed typical Trichophyton mentagrophytes. The patient was treated with 250 mg of terbinafine, 10 mg of prednisolone and 300 mg of roxithromycin daily for the first week, then 250 mg of terbinafine combined with topical lanoconazole for 4 weeks. The skin lesions improved 5 weeks after treatment, and recurrence has not been observed.

A Case of Cutaneous alternariosis due to Alternaria alternata / 대한의진균학회지

Alternaria is a common saprophyte that is not usually pathogenic in humans. However, infections by the fungus have occasionally been documented, occurring mostly in immunocompromised patients. We report a case of cutaneous alternariosis caused by Alternaria alternata in a 64-year-old woman presenting with a coin-sized, slightly elevated, dark red plaque on the right wrist without systemic immunosuppression. Macroscopic and microscopic morphology of fungal culture and histopathological differentiation offered diagnostic possibility. Systemic roxithromycin and itraconazole were administered with a dramatic resolution of the lesion.

Incidencia, diagnóstico, manejo y evolución de las neumonías atípicas en el Hospital Militar Cap. (Av) Guillermo Hernández Jacobsen: enero 1999-mayo 2006 / Incidence, diagnosis, management and development of atypical pneumonia at the Military Hospital Cap. (Av)Guillermo Hernández Jacobsen: january 1999-may 2006

Se realiazó un estudio descriptivo, retrospectivo y observacional mediante la revisión de 35 historias médicas de pacientes hospitalizados con Neumonía Atípica entre enero de 1999 y mayo de 2006. El grupo etáreo más afectado fue el de 15 a 39 años de edad, que representa el 54.2 por ciento. Los síntomas más frecuentes fueron de origen respiratorio, como son tos (32.5 por ciento) y disnea (26.25 por ciento). El 22.8 por ciento resultó positivo para Mycoplasma y el 20 por ciento para Chlamydia. Al momento del ingreso, se manejó con amtibioticoterapia basada en Levofloxacina en un 29.7 por ciento. Claritromicina en un 16.2 por ciento. Se observo evolución satisfactoria en el 82.8 por ciento de los casos en estudio.

Retraction: Roxithromycin Treatment of Tsutsugamushi Disease (Scrub Typhus) in Children / 소아과

No abstract available.

The effect of milk on plasmatic and tissue levels of macrolides: in vivo study in rats

The ingestion of milk with drugs, particularly some antibiotics, is frequently recommended in order to decrease possible gastrointestinal discomfort. The objective of this sutdy was to assess the interference of milk in the absorption and tissue levels of macroline antibiotics (erythromycin, clarithromycin, roxithromycin and azithromycin). Forty female rats received surgically-implanted PVC sponges on their backs. One week later, granulomatous tissue was observed and the animals were divided into eight groups, which received erythromycin, clarithromycin, roxithromycin and azithromycin with and without milk. One hour after administration of antibiotic, the animals were sacrificed. The serum and tissue samples were submitted to microbiological assay with Micrococcus luteus ATCC 9341, in order to determine drug concentration. Milk did not cause any reduction in the serum and tissue levels of azithromycin and clarithromycin (p>0.05, t-test). However, ingestion of milk reduced by approximately 28.7% the roxithromycin (p<0.0001, t-test) and by 34.1% the rythromycin (p<0.0001, t-test) serum concentrations. Similar effects were observed on tissue levels. Milk ingestion caused a reduction of approximately 20.8% in the roxithromycin (p<0.0001, t-test) and 40% in the erythromycin (p<0.0001, t-test) tissue levels. We concluded that erythromycin and roxithromycin should be not administered with milk

A Case of Acute Respiratory Distress Syndrome by Nosocomial Mycoplasma Pneumonia Associated with Cold Agglutinin Disease in Primary CNS Lymphoma / 감염과화학요법

Although Mycoplasma pneumonia is frequently observed in immunocompromized patient if, rarely results in acute respiratory distress syndrome (ARDS). The cold agglutinin is positive in 33-76% of patients with M. pneumonia infection. We experienced a case of ARDS due to mycoplasma pneumonia associated with cold agglutinin disease in primary CNS lymphoma. He was a 60-year old primary CNS lymphoma patient with mycoplasma pneumonia and cold agglutinin disease who rapidly progressed to ARDS after 1 cycle of chemotherapy. He completely recovered with roxithromycin, levofloxacin, and ventilator supports. After recovery 2nd cycle of combination chemotherapy and brain radiation therapy was given and, CNS lymphoma is in complete remission until now.

A Case of Acute Respiratory Distress Syndrome by Nosocomial Mycoplasma Pneumonia Associated with Cold Agglutinin Disease in Primary CNS Lymphoma / 감염과화학요법

Although Mycoplasma pneumonia is frequently observed in immunocompromized patient if, rarely results in acute respiratory distress syndrome (ARDS). The cold agglutinin is positive in 33-76% of patients with M. pneumonia infection. We experienced a case of ARDS due to mycoplasma pneumonia associated with cold agglutinin disease in primary CNS lymphoma. He was a 60-year old primary CNS lymphoma patient with mycoplasma pneumonia and cold agglutinin disease who rapidly progressed to ARDS after 1 cycle of chemotherapy. He completely recovered with roxithromycin, levofloxacin, and ventilator supports. After recovery 2nd cycle of combination chemotherapy and brain radiation therapy was given and, CNS lymphoma is in complete remission until now.