RESUMO
OBJECTIVE: To compare dispensed oral antibiotic prescription rates (DAPRs) after implementation of pneumococcal conjugate vaccine (PCV) in high antibiotic-prescribing clinics (HPC) with low antibiotic-prescribing clinics (LPC) in 2 distinct ethnic groups of children (Jewish and Bedouin children) <5 years of age. METHODS: Clinics with ≥50 insured children, active both pre-PCV (2005-2009) and post-PCV (2010-2018) implementation, were included. HPC and LPC were defined by DAPRs above or below the median in each age and ethnic group. Monthly dispensed antibiotic prescription rate (DAPR) trends (adjusted for age and ethnicity) were calculated using interrupted time series. Mean yearly incidence rate-ratios (late PCV13 vs pre-PCV) were calculated. RESULTS: Bedouin HPC had the highest pre-PCV overall-DAPR per 1000 child-years ± SD (2520.4 ± 121.2), followed by Jewish HPC (1885.5 ± 47.6), Bedouin LPC (1314.8 ± 81.6), and Jewish LPC (996.0 ± 19.6). Shortly after PCV implementation, all DAPRs and amoxicillin/amoxicillin-clavulanate DAPRs declined in all groups except Jewish LPC, stabilizing within 4-5 years post-PCV. The rates and magnitudes of declines were directly proportional to the pre-PCV DAPR magnitudes, achieving near-complete closure of the pre-PCV DAPR gaps between the 4 groups (rates during late-PCV13 ranging from 1649.4 ± 23.5 [Bedouin HPC] to 1200.3 ± 72.4 [Jewish LPC]). CONCLUSIONS: PCVs are a powerful tool in reducing outpatient antibiotic consumption among young children, especially in HPC, resulting in partial closure of DAPR gap between HPC and LPC. The higher impact on HPC suggests that PCV-associated declines of respiratory disease may strongly contribute to a judicious antibiotic approach in clinics with high antibiotic consumption.
Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Criança , Humanos , Lactente , Pré-Escolar , Vacinas Pneumocócicas/uso terapêutico , Antibacterianos/uso terapêutico , Vacinas Conjugadas , Combinação Amoxicilina e Clavulanato de Potássio , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controleRESUMO
OBJECTIVE: To determine the association between parents' level of education and delay in vaccination among infants and toddlers. STUDY DESIGN: A case-control study done in 2015-2016. Charts of 2- to 4-year-old children vaccinated in 5 neighborhood Maternal-Child Health Centers (MCHCs) in southern Israel were examined for demographic variables. Five vaccination opportunities between age 7 months and 18 months were selected to test for delays. In each MCHC, children vaccinated at the longest time-period after planned vaccination dose (fifth quintile) were compared with those vaccinated during the middle quintile. Using this relative delay approach rather than absolute delay approach permitted us to adjust the findings to the prevailing environmental and to cultural and programmatic variations between the various neighborhoods. Each of the planned vaccination visits and overall, demographic and health behavior-related variables that were significantly associated to delays by univariate analysis were tested by multivariate analysis and further adjusted by using stepwise logistic regression, using goodness of fit measures. RESULTS: Data for 2072 subjects were collected (398-426 per MCHC). Fathers' education was not associated with delays. In contrast, mothers' education was inversely associated with the probability of vaccination delay by 4%-9% (depending on the vaccination visit) for each year of schooling beyond 10 years. CONCLUSION: Using the relative delay approach, we demonstrated that maternal education, measured by schooling years, was independently inversely associated with risk of vaccination delay. This suggests that education can be regarded as an important positive component of the overall disease prevention planning at national and global levels.
Assuntos
Escolaridade , Mães/educação , Vacinação/estatística & dados numéricos , Adulto , Estudos de Casos e Controles , Pré-Escolar , Pai , Feminino , Humanos , Esquemas de Imunização , Israel , Judeus , Masculino , Fatores SocioeconômicosRESUMO
OBJECTIVE: To assess rotavirus vaccine and pneumococcal conjugate vaccines (PCVs) cumulative impact on the pediatric emergency department visits and hospitalization rates in children <2 years of age in southern Israel between April 2006 and March 2014. STUDY DESIGN: This prospective, population-based observational study calculated the rates of rotavirus gastroenteritis (RVGE), non-RVGE, community-acquired alveolar pneumonia (CAAP), nonalveolar lower respiratory tract infection, and all-cause hospital visits. PCV7, PCV13, and rotavirus vaccination programs were implemented in Israel in July 2009, November 2010, and January 2011, respectively. RESULTS: From 2006-2009 to 2013-2014, the rates of hospitilizations for RVGE, non-RVGE, CAAP, and nonalveolar lower respiratory tract infection decreased by 78%, 21%, 46%, and 7%, respectively. In outpatients, the respective decreases were 80%, 16%, 67%, and 14%. All-cause outpatient pediatric emergency department visits and hospitalization rates were reduced by 12% and 11%, respectively. During the peak season (October through March), RVGE, non-RVGE, CAAP, and nonalveolar lower respiratory tract infection hospitalization rates decreased significantly by 86%, 44.6%, 23.3%, and 10.5%, respectively. In outpatients, the respective decreases were 81.7%, 73.5%, 13.8%, and 10.7%. The proportion of RVGE and CAAP (grouped) of all-cause hospitalizations and outpatient pediatric ED visits decreased from 19.9% to 12.3% and from 6.9% to 1.8%, respectively. CONCLUSIONS: Rotavirus vaccine and PCV introduction cocontributed to a rapid, considerable reduction in hospital burden in children <2 years of age. Because seasonalities of both diseases overlap, this reduction is particularly helpful in relieving burdens of disease and care during the most cumbersome morbidity season.
Assuntos
Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Fatores Etários , Pré-Escolar , Estudos de Coortes , Intervalos de Confiança , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Incidência , Lactente , Israel/epidemiologia , Masculino , Razão de Chances , Avaliação de Resultados em Cuidados de Saúde , Infecções Pneumocócicas/epidemiologia , Estudos Prospectivos , Medição de Risco , Infecções por Rotavirus/epidemiologia , Distribuição por Sexo , Fatores Sexuais , VacinaçãoRESUMO
Acute otitis media (AOM) microbiology was evaluated in children after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector, 2004; National Immunization Program, 2009). This was a combined prospective and retrospective study conducted in a routine clinical setting in San José, Costa Rica. In the prospective part of the study, which was conducted post-PCV7 introduction (2010-2012), standard bacteriological procedures were used to evaluate the etiology and serotype distribution of middle ear fluid samples collected by tympanocentesis or otorrhea from children aged 3-59 months diagnosed with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture-positive samples. Retrospective data recorded between 1999 and 2004 were used for comparison of bacterial etiology and serotype distribution before and after PCV7 introduction. Statistical significance was evaluated in bivariate analyses at the P-value < 0.05 level (without multiplicity correction). Post-PCV7 introduction, Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in 87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H. influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%) frequently observed in vaccinated (≥ 2 PCV7 doses or ≥ 1 PCV7 dose at >1 year of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were 1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non-susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7 introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S. pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value = 0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9.7%), 6B (9.7%), and 14 (9.7%) pre-PCV7 introduction, and 19F (27.6%), 14 (8.0%), and 35B (8.0%) post-PCV7 introduction. Following PCV7 introduction, a change in the distribution of AOM episodes caused by H. influenzae and pneumococcal serotypes included in PCV7 was observed in Costa Rican children. Pneumococcal vaccines impact should be further evaluated following broader vaccination coverage.
Assuntos
Antibacterianos , Haemophilus influenzae , Programas de Imunização , Otite Média com Derrame , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae , Doença Aguda , Antibacterianos/classificação , Antibacterianos/uso terapêutico , Pré-Escolar , Costa Rica/epidemiologia , Feminino , Haemophilus influenzae/classificação , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/isolamento & purificação , Humanos , Programas de Imunização/métodos , Programas de Imunização/estatística & dados numéricos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Otite Média com Derrame/epidemiologia , Otite Média com Derrame/microbiologia , Otite Média com Derrame/fisiopatologia , Otite Média com Derrame/prevenção & controle , Paracentese/métodos , Prevalência , Sorotipagem , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , Resultado do Tratamento , Vacinas Conjugadas/administração & dosagemRESUMO
Justificación y objetivo: Streptococcus pneumoniae es globalmente la primera causa de muertes inmunoprevenibles en niños menores de 5 años. Métodos: entre 2007 y 2009 se realizó una vigilancia prospectiva con base poblacional en niños de 28 días a 36 meses en San José, Costa Rica. Se determinaron la incidencia de la enfermedad neumocócica invasora y de neumonía confirmada clínicamente y por radiografía, la distribución de serotipos y la sensibilidad a los antibióticos. Resultados: participaron 8801 sujetos (mediana de edad: 13,0 meses). En 25 niños se detectó enfermedad neumocócica invasora mediante aislamiento en cultivos (22) o mediante reacción de polimerasa en cadena y un cuadro clínico compatible con enfermedad neumocócica invasora. En los casos diagnosticados únicamente por cultivo, la tasa de incidencia de enfermedad neumocócica invasora en niños de 28 días a 36 meses de edad fue de 33,7/100000 por año para los años 1 y 2 combinados. Al considerar los casos adicionales diagnosticados por reacción de polimerasa en cadena, la incidencia aumnetó a 46,/100 000. El serotipo más frecuente fue el 14 (28,6 por ciento), seguido por los serotipos 3, 4, 6A, 19A, 22F. 42,9 por ciento de los aislamientos eran insensibles a la penicilina y al cotrimoxazol. La incidencia de neumonía confirmada clínicamente y de neumonía confirmada por radiografía fue de 1968/100 000 y 551/100 000, respectivamente. Conclusión: la incidencia de enfermedad neumocócica invasora y neumonía en niños de San José es considerable. Estos datos epidemiológicos sirven como línea de base para evaluar la efectividad de nuevas vacunas antineumocócicas conjugadas.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Costa Rica , Infecções Pneumocócicas/diagnóstico , Infecções Pneumocócicas/etiologia , Infecções Pneumocócicas/prevenção & controle , Infecções Pneumocócicas/tratamento farmacológico , Infecções PneumocócicasRESUMO
BACKGROUND: The heptavalent pneumococcal conjugate vaccine (PCV-7) was introduced in high risk children and into the private market in Costa Rica in 2004 (<5% annual birth cohort). The aim of this study was to compare the Streptococcus pneumoniae serotype (ST) distribution, antibiotic resistance patterns and potential coverage before and after partial introduction of PCV-7. METHODS: A comparison between the S. pneumoniae isolates obtained and serotyped from the middle ear fluid (MEF) of Costa Rican children with otitis media between years 1999 and 2003 (before PCV-7 usage) and those isolates obtained from 2004 to 2008. RESULTS: A total of 145 and 218 MEF S. pneumoniae were serotyped between years 1999 and 2003 and 2004 and 2008, respectively. Considering a 19F outbreak observed between years 1999 and 2003, the following statistically significant changes in serotype distribution were detected between 1999 and 2003 and 2004 and 2008: ST 3: 4.8-12.8% (P=0.01); ST 11A: 0-4.1% (P=0.01); ST 14: 3.5-21.1% (P<0.001) and ST 19F: 52.4-18.3% (P<0.05). Comparison of the two study periods demonstrated that during 2004 and 2008 a statistically significant decrease in penicillin non-susceptible serotypes (36.2-20.4% [P=0.003]) and a statistically significant increase in trimethoprim-sulfametoxazole resistant serotypes (54.9-68.5%, respectively [P=0.03]) was observed. Potential pneumococcal vaccines coverage between 1999 and 2003 and between 2004 and 2008 were: for PCV-7: 77.2-60.5%, respectively (P=0.001); for the 10-valent conjugated vaccine (PCV-10): 78.6-61.4%, respectively (P=0.0008) and for the 13-valent conjugated vaccine (PCV-13): 84.8-79.3%, respectively (P=0.2). CONCLUSIONS: Changes in the serotype distribution and antimicrobial susceptibility of MEF S. pneumoniae have been observed in Costa Rican children with OM. Because of the limited use of PCV-7 during the study period, these changes probably cannot be attributed to PCV-7 use. Between 2004 and 2008, PCV-13 offered the highest potential vaccine coverage.
Assuntos
Otite Média/epidemiologia , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Antibacterianos/farmacologia , Criança , Pré-Escolar , Costa Rica/epidemiologia , Farmacorresistência Bacteriana , Orelha Média/microbiologia , Feminino , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Otite Média/microbiologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/administração & dosagem , Sorotipagem , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/imunologiaRESUMO
BACKGROUND: Streptococcus pneumoniae (SP) is the leading cause of vaccine-preventable death in children <5 years of age, globally. This surveillance determined incidence rates of invasive pneumococcal disease (IPD), clinical and chest radiograph-confirmed pneumonia (CXR+Pn); and SP serotype distribution and antimicrobial susceptibility in children in San José, Costa Rica. METHODS: This was a 2-year prospective, population-based surveillance conducted in 2007-2009 in children aged 28 days to 36 months presenting to participating healthcare centers. Eligibility criteria for study inclusion were as follows: temperature ≥ 39.0°C within 24h and/or clinical suspicion of IPD or pneumonia. RESULTS: 8801 subjects were enrolled. Median age: 14.5 months. A total of 25 children had invasive pneumococcal disease with S. pneumoniae isolated from nonduplicative cultures (22) or detected solely by PCR and a clinical picture consistent with IPD (3). Sources of positive cultures (some children had >1 positive culture) were: blood (20), pleural fluid (4), and cerebrospinal fluid (3). Of the 3 cases detected solely by PCR, 2 were from cerebrospinal fluid and 1 from pleural fluid. The overall IPD incidence rates for culture-positive only cases for children aged 28 days to <3 years was 33.7/100,000 per year for years 1 and 2 combined. Age stratification of culture-positive only subjects showed a peak during year 1 (106.8/100,000) in children 28 days to <6 months of age group, and in year 2 (45.5/100,000) in children 12 months to <24 months of age group. Most common serotypes were 14 (28.6%), followed by 3, 4, 6A, 19A, and 22F (9.5% each). Of 22 nonduplicative IPD isolates, 42.9% were penicillin- and trimethoprim/sulfamethoxazole nonsusceptible isolates. Consideration of PCR-positive cases increases the incidence of IPD for children aged 28 days to <3 years to 46.0/100,000. Overall incidence of clinical pneumonia and CXR+Pn was 1968/100,000 and 551/100,000, respectively. CONCLUSIONS: There is a considerable burden of IPD and pneumonia in children in San José. These epidemiologic data serve as a baseline to evaluate the effectiveness of the incorporation of new conjugate pneumococcal vaccines into the National Immunization Program in Costa Rican children.
Assuntos
Infecções Pneumocócicas/epidemiologia , Pneumonia Pneumocócica/epidemiologia , Vigilância da População/métodos , Streptococcus pneumoniae/isolamento & purificação , Antibacterianos/farmacologia , Pré-Escolar , Costa Rica/epidemiologia , Meios de Cultura , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Infecções Pneumocócicas/microbiologia , Pneumonia Pneumocócica/microbiologia , Reação em Cadeia da Polimerase/métodos , Estudos Prospectivos , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genéticaRESUMO
OBJECTIVES: To determine the involvement of human metapneumovirus (HMPV) in childhood community-acquired alveolar pneumonia (CAAP) and compare the demographic, clinical, and laboratory features of HMPV-associated CAAP and CAAP associated with other respiratory viruses. STUDY DESIGN: Nasopharyngeal wash specimens obtained prospectively over a 4-year period from children age < 5 years evaluated in the emergency department with radiologically diagnosed CAAP and from healthy controls were tested for HMPV by reverse-transcriptase polymerase chain reaction and for respiratory syncytial virus (RSV), adenovirus, influenza and parainfluenza viruses by direct immunofluorescence and culture. RESULTS: HMPV was detected in 108 of 1296 patients (8.3%) versus RSV in 23.1%, adenovirus in 3.4%, influenza A virus in 2.9%, and parainfluenza viruse in 2.9%. During the period of peak activity (November to May), HMPV was detected in 95 of 1017 patients (9.3%) and in 3 of 136 controls (2.2%) (P = .005). The patients with HMPV were older than those with RSV (P < .001) with a more common history of acute otitis media requiring tympanocentesis (P = .032), wheezing (P = .001) and gastrointestinal symptoms (P < .001) and a lower hospitalization rate (P = .005). CONCLUSIONS: The high detection rate suggests an important role for HMPV in childhood CAAP. Our findings identify demographic and clinical features of HMPV-positive CAAP and its age-related impact on hospital admissions.
Assuntos
Metapneumovirus , Infecções por Paramyxoviridae/epidemiologia , Pneumonia Viral/virologia , Pré-Escolar , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/virologia , Comorbidade , Feminino , Humanos , Lactente , Masculino , Numismática , Reação em Cadeia da Polimerase , Estudos Prospectivos , Alvéolos Pulmonares/virologiaRESUMO
BACKGROUND: Because the microbiology and susceptibility patterns of middle ear fluid pathogens in children with otitis media change over time, an active surveillance is recommended to establish appropriate therapeutic guidelines. OBJECTIVE: To analyze the microbiology and susceptibility pattern of middle ear pathogens obtained from Costa Rican children with acute otitis media (AOM), recurrent otitis media (ROM) and therapeutic failure otitis media (OMTF) between 2002 and 2007. PATIENTS AND METHODS: 1108 children aged 2-92 months who participated in various otitis media clinical trials between the years 2002 and 2007. RESULTS: Among the study population, 880 were children with AOM (61% <24 months of age), 138 were children with ROM (54% <24 months of age) and 90 were children with OMTF (67% <24 months of age). Bilateral otitis media was more frequent in children with OMTF (44%) than in children with AOM (37%) (P=0.19) and ROM (27%) (P=0.009). Presence of siblings <8 years of age was more frequently observed in children with OMTF (73%) than in children with ROM (65%) (P=0.0001) and AOM (47%) (P=0.000002). Overall Streptococcus pneumoniae (44%) was the most common pathogen isolated followed by Haemophilus influenzae (37%), Moraxella catarrhalis (11%) and Streptococcus pyogenes (4%). S. pneumoniae was the most common pathogen in AOM (44%) and ROM (47%), however, H. influenzae was the most common pathogen in OMTF (40%). Among all H. influenzae, an increase in the number of ß-lactamase producing strains was observed from 5.2% in 2001 to 14% (P=0.04) in 2007 and this was associated with an increase in the use of amoxicillin. An increase in the number of M. catarrhalis was also observed, from 3% (9/350) in 2001 to 11% (71/628) (P=0.000003) in 2007. During the study period the incidence of penicillin non-susceptible S. pneumoniae was 42/211 (20%) in children with AOM; 5/35 (17%) in children with ROM and 5/17 (42%) in children with OMTF. M. catarrhalis cases increased from 8% in 2004 to 17% in 2007 (P=0.0005) and S. pyogenes decreased from 7% in 2002-2004 to 1% in 2005-2007 (P=0.001). CONCLUSIONS: In Costa Rica, S. pneumoniae remains the most common pathogen in children with AOM and ROM whereas non-typable H. influenzae remains the most common pathogen in children with OMTF. A significant increase in the number of ß-lactamase positive H. influenzae and M. catarrhalis has been observed in recent years.
Assuntos
Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Otite Média com Derrame/epidemiologia , Otite Média com Derrame/microbiologia , Doença Aguda , Antibacterianos/uso terapêutico , Distribuição de Qui-Quadrado , Pré-Escolar , Estudos de Coortes , Costa Rica/epidemiologia , Feminino , Seguimentos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Incidência , Lactente , Masculino , Testes de Sensibilidade Microbiana , Otite Média/tratamento farmacológico , Otite Média/epidemiologia , Otite Média/microbiologia , Otite Média com Derrame/tratamento farmacológico , Estudos Retrospectivos , Medição de Risco , Resultado do TratamentoRESUMO
BACKGROUND: After the introduction of the seven valent-pneumococcal conjugated vaccine into our National Immunization Program, it is important to establish and track local serotype distribution in order to evaluate its impact specially because serotype replacement phenomena has been described.To describe the clinical, epidemiological and antimicrobial resistance patterns of Costa Rican children with otitis media caused by Streptococcus pneumoniae serotype 3. METHODS: Middle ear fluid samples were obtained from Costa Rican children with otitis media who participated in various antimicrobial clinical trials between 1992 and 2007. Streptococcus pneumoniae was identified according to laboratory standard procedures. Strains were serotyped and antimicrobial susceptibility to penicillin, amoxicillin, cefuroxime, ceftriaxone, azithromycin and levofloxacin was determined by E-test. RESULTS: Throughout 1992-2007 a total of 1919 tympanocentesis were performed in children with otitis media (median age: 19 months) and yielded a total of 1208 middle ear isolates. The most common pathogens were: Streptococcus pneumoniae, 511 isolates (49%); Non-Typable Haemophilus influenzae, 386 isolates (37%); Moraxella catarrahalis, 100 isolates (9.5%); and Streptococcus pyogenes, 54 isolates (5%). Streptococcus pneumoniae serotyping was performed in 346/511 isolates (68%) recovered during years 1999-2006. The most common serotypes were 19F (101/30.0%), 14 (46/13.7%), 3 (34/10.1%), 6B (30/8.9%) and 23F (23/6.8%). Analysis performed per years showed a higher prevalence of serotype 3 Streptococcus pneumoniae during the study period 2004 and 2005. During the entire study period (1999-2006) serotype 3 was most commonly isolated in children older than 24 months (61.2% vs 40.6%;P = 0.05) and showed a lower rate of penicillin non-susceptibility (4.0% vs 18%; P = 0.003). CONCLUSION: Streptococcus pneumoniae serotype 3 is an important pathogen in Costa Rican children with otitis media, especially in children older than 24 months of age (P = 0.05). Most serotype 3 isolates were susceptible to penicillin, cephalosporins, macrolides and quinolones.