2006至2009年复旦大学附属儿科医院呼吸道感染患儿5种常见细菌构成比和耐药性分析

目的 了解复旦大学附属儿科医院4年中呼吸道感染患儿呼吸道标本中化脓性链球菌、肺炎链球菌、金黄色葡萄球菌、流感嗜血杆菌和卡他莫拉菌耐药率变化。方法 以2006至2009年在复旦大学附属儿科医院诊断为呼吸道感染的患儿为研究对象,采集咽拭子或痰标本行细菌培养。细菌鉴定采用NCCLS/CLSI 2006至2009年标准及英国BSAC标准。采用琼脂扩散法（KB）对5种常见细菌进行药物敏感实验,结果参照CLSI 2006至2009年标准,肺炎链球菌青霉素药物敏感实验采用E-test检测。结果 2006至2009年呼吸道标本中共分离到细菌3 169株,其中化脓性链球菌1 225株、肺炎链球菌341株、金黄色葡萄球菌297株、流感嗜血杆菌248株、卡他莫拉菌237株。①化脓性链球菌在上呼吸道细菌中构成比为74.5％~78.8％,流感嗜血杆菌和卡他莫拉菌在上下呼吸道细菌中的构成比有逐年上升趋势（P<0.05）。②2006至2009年,化脓性链球菌对红霉素耐药率为86.8％～94.7％,未发现青霉素耐药株;青霉素不敏感肺炎链球菌比例为1.4％~20.8％,4年间差异有统计学意义（P=0.007）,肺炎链球菌对红霉素耐药率为91.1％~97.9％;金黄色葡萄球菌对红霉素耐药率为50.0％~54.9％,耐甲氧西林金黄色葡萄球菌比例为7.7％~11.4％;上述3种细菌对万古霉素均敏感。流感嗜血杆菌和卡他莫拉菌β-内酰胺酶阳性率分别为17.0％~31.3％和83.1％~100％,流感嗜血杆菌对头孢呋辛耐药率较低,卡他莫拉菌对环丙沙星和阿莫西林/克拉维酸高度敏感。结论 化脓性链球菌和肺炎链球菌对青霉素高度敏感。化脓性链球菌、肺炎链球菌及金黄色葡萄球菌对红霉素高度耐药。产酶的流感嗜血杆菌对第2代头孢菌素高度敏感,卡他莫拉菌对喹诺酮类和酶抑制剂复合制剂高度敏感。     

2004年肺炎链球菌、流感嗜血杆菌和卡他莫拉菌耐药监测

目的监测2004年呼吸道常见致病菌肺炎链球菌、流感嗜血杆菌和卡他莫拉菌对抗生素的耐药性。方法抗生素药敏试验采用E_test法和K_B法。结果肺炎链球菌对青霉素不敏感率为32.9%,对头孢克洛、头孢呋辛和头孢曲松分别为25.0%、26.4%和5.7%,对红霉素、阿齐霉素和克林霉素不敏感率>90%;流感嗜血杆菌和卡他莫拉菌对氨苄青霉素耐药率分别为14.3%和56.6%,但前者β_内酰胺酶阳性率为14.3%,而后者为90.8%,两者对其他β_内酰胺酶类耐药率较低。结论呼吸道致病菌对抗生素的耐药性正在增加,连续监测抗生素的耐药性对经验治疗呼吸道感染非常必要。     

急性呼吸道感染住院患儿细菌病原学分析

目的探讨苏州地区住院儿童急性呼吸道感染细菌病原学分布。方法对2005年11月至2007年10月在苏州大学附属儿童医院住院治疗的所有急性呼吸道感染患儿,常规进行深部痰培养,进行病原学分析。结果急性呼吸道感染患儿共3069例,其中881例分离到1种或1种以上致病菌,阳性率为28.7%,最常见的病原菌为肺炎链球菌、流感嗜血杆菌、金黄色葡萄球菌和卡他莫拉菌,阳性率分别为10.1%,4.3%,3.7%和2.7%,连续两年病原总阳性率呈增长趋势。总病原阳性率以1个月至1岁最高,为32.8%。流感嗜血杆菌、卡他莫拉菌、大肠埃希菌、肺炎克雷伯杆菌和真菌检出率以低龄组为主。卡他莫拉菌、流感嗜血杆菌和铜绿假单胞菌四季检出率不同。流感嗜血杆菌男性检出率高于女性。结论肺炎链球菌、流感嗜血杆菌、金黄色葡萄球菌和卡他莫拉菌是小儿急性呼吸道感染常见致病菌。     

中国2岁以下健康婴幼儿鼻咽部携带常见病原菌的血清分型及耐药性分析

目的分析2岁以下健康婴幼儿鼻咽部携带肺炎链球菌的血清型特点,监测肺炎链球菌、流感嗜血杆菌、卡他莫拉菌对常规用药的体外敏感性。方法采用荚膜肿胀试验对肺炎链球菌进行血清分型,E-test法测定肺炎链球菌(451株)、流感嗜血杆菌(168株)、卡他莫拉菌(396株)的体外敏感性,头孢硝噻吩试验检测流感嗜血杆菌、卡他莫拉菌β内酰胺酶的产生情况。结果肺炎链球菌、流感嗜血杆菌和卡他莫拉菌的携带率分别为12.4%、4.6%、10.9%;肺炎链球菌血清分型中19F最多见,其余依次为14、19A和15、6B、23F、6A,且春季和秋冬季无明显差别;PCV7、PCV9、PCV10价疫苗覆盖率均为48.6%,PCV13覆盖率为61.0%,后者明显高于前者;此外,19A的耐药性高于多数血清型(包括19F),23F的耐药性强于其他血清型,6A的耐药性强于6B。不同城市间青霉素耐药肺炎链球菌、青霉素中介肺炎链球菌、青霉素敏感肺炎链球菌所占比例分别为11.6%～28.6%、19.6%～54.4%、32.0%～62.8%。流感嗜血杆菌和卡他莫拉菌对大部分抗菌药物敏感,22.7%和21.0%的卡他莫拉菌对红霉素和阿奇霉素耐药,济南的耐药率高达50.0%和44.8%。卡他莫拉菌β-内酰胺酶阳性率为85.0%～100.0%;未发现β-内酰胺酶阴性氨苄西林耐药的流感嗜血杆菌。结论 2岁以下健康婴幼儿鼻咽部携带肺炎链球菌中以19F最多见,19A耐药性强于其他血清型;肺炎链球菌、流感嗜血杆菌及卡他莫拉菌对常用抗生素的耐药性增加,应引起高度重视。     

2016~2018年儿童呼吸道感染病原菌谱与耐药监测

目的 了解儿童呼吸道感染的病原菌种类、分布特点和耐药情况，为临床提供病原学诊断及合理使用抗菌药物的依据。方法 选取2016年1月至2018年12月因呼吸道感染就诊的15 047例患儿为研究对象，采集患儿痰标本送检，通过Phoenix-100全自动微生物鉴定药敏系统对分离的病原菌进行鉴定和药敏分析。结果 从17 174份送检的痰标本中检出阳性标本2 395份，阳性率为13.95%；共分离出2 584株病原菌，其中革兰阴性菌1 577株（61.03%），革兰阳性菌967株（37.42%），真菌40株（1.55%）。最常见的病原菌依次为流感嗜血杆菌（33.90%）、肺炎链球菌（33.55%）、卡他莫拉菌（19.20%）和金黄色葡萄球菌（3.64%）。2 331例感染阳性患儿中有251例混合感染，以流感嗜血杆菌合并肺炎链球菌感染发生率最高。病原菌检出率以冬春季较高，夏秋季较低（P < 0.05）。各年龄组患儿病原菌检出率比较差异有统计学意义（P < 0.05），其中1个月~ < 1岁组患儿病原菌检出率最高。肺炎链球菌和金黄色葡萄球菌对万古霉素、利奈唑胺和替考拉宁敏感率均为100%，流感嗜血杆菌除对氨苄西林、复方新诺明和头孢呋辛敏感率较低，对其他药物敏感率均较高。结论 儿童呼吸道感染病原菌以流感嗜血杆菌、肺炎链球菌和卡他莫拉菌为主，且常见混合型感染。不同季节、不同年龄段病原菌检出率不同。不同病原菌耐药性有不同特点，临床应依据药敏结果合理选用抗生素。     

化脓性中耳炎病原学研究

为了解小儿化脓性中耳炎主要致病菌及其对抗生素的敏感情况，对５７例化脓性中耳炎患儿的中耳分泌物进行培养后，采用改良的Ｋｉｒｂｙ－Ｂａｕｅｒ纸片琼脂扩散法，对所获得的致病菌进行药物敏感试验。结果：共分离出６０株致病菌，主要有肺炎链球菌和流感嗜血杆菌，各１９株（３１．７％），Ａ族链球菌１０株（１６．７％）；肺炎链球菌对复方新诺明和红霉素的耐药率分别为９４．７％和６３．２％，对青霉素和头孢菌素均敏感，而流感嗜血杆菌对青霉素耐药率为３６．８％，对第１代头孢菌素耐药率则达６０％左右。提示：肺炎链球菌和流感嗜血杆菌是小儿化脓性中耳炎的主要致病菌；前者除对复方新诺明和红霉素耐药率较高外，对β－内酰胺类均敏感，因此青霉素类仍为肺炎链球菌中耳炎的首选药物；流感嗜血杆菌则存在着严重的耐药倾向。     

卡他莫拉菌研究进展

卡他莫拉菌是儿童上颌窦炎、中耳炎、肺炎等呼吸道感染的第3位常见致病菌,仅次于流感嗜血杆菌和肺炎链球菌,目前产酶耐药株比例已超过90%.卡他莫拉菌通过产生BRO 内酰胺酶对青霉素耐药.卡他莫拉菌产生的内酰胺酶分为BRO-1、BRO-2及BRO-3,由染色体基因编码,而且编码基因较易在细菌间转移.与其他已知β内酰胺酶不同,BRO基因是卡他莫拉菌新近获取的外源基因,21个新突变发生于BRO基因的启动子.     

儿童呼吸道病原菌的抗生素耐药问题

在过去的２０年中，儿童呼吸道病原菌的耐药问题日益严重，对氨苄青霉素耐药的流感嗜血杆菌广泛流行，大多数临床分离到的卡他莫拉菌产生β－内酰胺酶，因此有可能对氨苄青霉素及阿莫西林耐药。Ａ族β型溶血性链球菌在体外仍对青霉素保持敏感，然而青霉素耐受青霉素治疗失败的报道在增多，其红霉素耐药菌株在很多国家流行。与此同时肺炎链球菌的青霉素耐药率于８０年代后期在世界各地急剧升高，青霉素结合蛋白得到进一步修饰的肺炎链球菌株已经出现，即使是广谱的第三代头孢菌素对它也缺乏效力。这些变化应该引起临床儿科医生的注意并对目前临床抗生素的使用加以探讨。     

学龄前儿童肺炎链球菌和卡他莫拉菌携带状态及影响因素分析北大核心CSCD

目的了解学龄前儿童肺炎链球菌和卡他莫拉菌的携带状态及影响因素。方法采用分层整群抽样方法抽取广东省佛山市顺德区7所幼儿园中共2031名健康儿童为研究对象,对所有儿童进行鼻拭子采样并分离鉴定肺炎链球菌和卡他莫拉菌。分析儿童肺炎链球菌和卡他莫拉菌的不同携带状态与其人口学特征、医院/社区相关因素的关系。结果学龄前儿童鼻腔肺炎链球菌携带率为21.81%,卡他莫拉菌携带率为52.44%,肺炎链球菌和卡他莫拉菌的共携带率为14.87%。对应分析表明,低年龄班、外市户籍、现居住农村、居住面积小、有呼吸道感染史且无抗生素使用史、有过敏性皮肤病、无医院相关暴露史与儿童肺炎链球菌和卡他莫拉菌的共携带显著相关(P<0.05)。结论学龄前儿童存在肺炎链球菌和卡他莫拉菌的共携带现象;年龄小、不良的居住环境、有呼吸道感染史且无抗生素使用史、有过敏性皮肤病、无医院相关暴露史是学龄前儿童肺炎链球菌和卡他莫拉菌共携带的重要危险因素。[中国当代儿科杂志,2022,24(8):874-880]     

2003-2004年广州地区儿童肺炎链球菌、流感嗜血杆菌抗生素敏感性调查

目的了解2003-2004年广州地区儿童呼吸道感染常见病原肺炎链球菌和流感嗜血杆菌对常用抗生素的敏感性,以便有效指导临床合理用药和预防.方法对2003-2004年在广州市儿童医院就诊的1565例上呼吸道感染儿童鼻咽分泌物进行培养,分离肺炎链球菌和流感嗜血杆菌;采用纸片扩散法及E-test方法对分离株进行常用抗生素敏感性检测.结果从1565例呼吸道感染儿童鼻咽部分离肺炎链菌球共172株,流感嗜血杆菌484株.172株肺炎链球菌对常用抗生素耐药株数（耐药率）分别为：青霉素55（32.0%）、阿莫西林/克拉维酸19（11.1%）、头孢曲松56（32.6%）、头孢呋辛31（18.1%）、头孢克洛68（39.5%）、红霉素142（82.6%）、四环素135（78.5%）、氯霉素42（24.4%）、复方磺胺甲基异噁唑150（87.2%）、克林霉素119（69.2%）、氧氟沙星5（3.1%）;肺炎链球菌的青霉素不敏感株对β-内酰胺类、红霉素、复方磺胺甲基异噁唑耐药率明显高于青霉素敏感株,且多重耐药率在90%以上.484株流感嗜血杆菌中,143株β-内酰胺酶阳性,产酶率为29.5%,484株流感嗜血杆菌的耐药株数（耐药率）分别为：氨苄西林194（40.1%）,阿莫西林/克拉维酸16（3.4%）、头孢曲松20（4.1%）、头孢呋辛9（1.9%）、头孢克洛27（5.6%）、复方磺胺甲基异噁唑272（56.2%）、四环素252（52.1%）、氯霉素84（17.4%）、阿奇霉素10（2.1%）、氧氟沙星3（0.6%）.结论广州地区儿童呼吸道肺炎链球菌和流感嗜血杆菌耐药形势严峻,与该地区前3年资料比较,肺炎链球菌对青霉素敏感性有所增加,但对头孢曲松耐药性增加,青霉素不敏感株的多重耐药率较高,以红霉素、四环素、复方磺胺甲基异噁唑多重耐药为主要特点.流感嗜血杆菌的产酶率上升,导致菌株对氨苄西林耐药性明显增高,对头孢二、三代抗生素、阿莫西林/克拉维酸、阿奇霉素有较高的敏感性.     

Microbiology of otitis media in Costa Rican children, 1999 through 2001

BACKGROUND: Because of the increasing number of resistant middle ear pathogens and the impact of the new conjugate Streptococcus pneumoniae vaccine, an active surveillance of the microbiology and susceptibility pattern of middle ear pathogens is required. OBJECTIVE: To study 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 (FOM). METHODS: Between 1999 and 2001 middle ear fluid (MEF) was collected from 276 Costa Rican patients. S. pneumoniae serotyping and pulsed field gel electrophoresis analysis was done on available strains. RESULTS: Among the total study population, 102 were AOM patients, 98 were ROM patients and 76 were FOM patients. Overall S. pneumoniae (88 strains) was the most common pathogen isolated followed by Haemophilus influenzae (41 strains) and Streptococcus pyogenes (10 strains). H. influenzae was the most common agent in FOM patients (P = 0.015). Beta-lactamase production was observed in 3 of 41 (7%) H. influenzae strains and 3 of 3 (100%) Moraxella catarrhalis strains. Penicillin-nonsusceptible S. pneumoniae strains were more common in FOM (64%) and ROM (63%) patients than in AOM (42%) patients (P = 0.05). S. pneumoniae serotype 19F was the most prevalent serotype, mainly within one distinct clone. CONCLUSIONS: Overall S. pneumoniae serotype 19F was the most common isolate from the middle ear fluid of Costa Rican children. Beta-lactamase-negative H. influenzae was the most prevalent in the subpopulation of patients with FOM. S. pyogenes was the third most common isolate and M. catarrhalis was uncommon.     

Clinical and bacterial characteristics of acute bacterial conjunctivitis in children in the antibiotic resistance era

BACKGROUND: Acute conjunctivitis is the most common eye disorder in young children. Bacteria are responsible for 54-73% of all cases. The goals of the study were to identify the rates of Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis in cases of bacterial conjunctivitis in children and to define antibiotic resistance rates. METHODS: During a 2-year study period, conjunctival swabs of children 2-36 months old were collected prospectively. Nontypable H. influenzae, S. pneumoniae and M. catarrhalis were defined as the study pathogens. Analyzed variables included demography, clinical presentation, bacteriologic results and susceptibility patterns. RESULTS: There were 428 patients enrolled. Of all cultures, 55% (237 of 428) yielded at least 1 of the study pathogens. H. influenzae and S. pneumoniae were isolated from 29 and 20% of cultures, respectively. beta-Lactamase production was found in 29% of H. influenzae isolates, and penicillin nonsusceptibility was observed in 60% of S. pneumoniae isolates. The most common S. pneumoniae serotypes were: 19F (14%); 6A and 14 (11% each). Nontypable S. pneumoniae was found in 12%. The 7-valent pneumococcal conjugate vaccine (PCV-7) could potentially cover 44% of all isolates. Conjunctivitis-otitis syndrome was found in 32% of patients, of whom 82% of cultures yielded H. influenzae. CONCLUSIONS: Antibiotic resistance rates are alarmingly high. Conjunctivitis-otitis syndrome, predominantly caused by H. influenzae, is quite common. The potential coverage of the PCV-7 in conjunctivitis is relatively lower than that reported in other pneumococcal infections. Our findings should alert physicians on the choice of appropriate antibiotic treatment, on the frequent copresence of acute otitis media and on the potential role of conjunctivitis in the spread of antibiotic-resistant pathogens.     

Bacteriological study of acute otitis media in children. Therapeutic consequences

One hundred children presenting with acute otitis media underwent a bacteriological study of otitis exudate over a 18 month period. The bacteria found were as follows: Streptococcus pneumoniae (24), Haemophilus influenzae (19), Staphylococcus aureus (12), Streptococcus pyogenes (7), Branhamella catarrhalis (3), and 18 Gram negative bacilli (including 7 Pseudomonas aeruginosa and 11 enterobacteriaceae). One pathogenic bacterium was isolated in 56 cases, 2 or more in 12 cases and none in 32 cases. In the age categories 0-1 year (47 cases) and 1-3 years (31 cases), S. pneumoniae and H. influenzae were the main organisms found, followed by S. pyogenes in children older than 3 years (22 cases). With respect to the antibiotics used for treating otitis, 5/22 S. pneumoniae and 4/17 H. influenzae were erythromycin resistant (9/17 had an intermediate susceptibility) and 7/19 H. influenzae and 1/17 S. pneumoniae were cotrimoxazole resistant. None of the S. pneumoniae and 2/19 H. influenzae were ampicillin resistant. These 2 H. influenzae and 2/3 B. catarrhalis were beta-lactamase producers. They were sensitive to the combination of amoxicillin with clavulanic acid.     

Seasonal distribution of otitis media pathogens among Costa Rican children

BACKGROUND: Otitis media is an important cause of pediatric consultation, and knowledge of yearly pathogen distribution might improve antimicrobial selection. OBJECTIVES: To determine the seasonal pathogen and antimicrobial resistance distribution among Costa Rican children with otitis media. METHODS: Between 1999 and 2004, 952 children with otitis media, aged 3-144 months who participated in various clinical trials, were analyzed. Data obtained from this period were compared against historical data collected between 1992 and 1997. RESULTS: Five hundred sixteen (52%) children had a baseline middle ear fluid pathogen isolated. The most common pathogens were Streptococcus pneumoniae 252 (49%), Haemophilus influenzae 190 (37%), S. pyogenes 38 (7%), and Moraxella catarrhalis 36 (7%). The overall proportion of H. influenzae (24-37%; P = 0.01) and the production of beta-lactamase producing H. influenzae (2.6-7%; P = 0.02) increased from 1992-1997 to 1999-2004. There was a nonstatistically significant trend for a higher frequency of S. pneumoniae and H. influenzae isolates detected during the rainy season than during the dry season: S. pneumoniae 58% versus 42% but not significant (P = 0.1) and H. influenzae 68% versus 32% (P = 0.06), respectively. During the rainy season, penicillin-nonsusceptible S. pneumoniae was identified more frequently (38.5%) than during the dry season (18%) (P = 0.003; odds ratio: 2.94; 95% confidence interval: 1.4-6.45). Penicillin-nonsusceptible S. pneumoniae decreased from 46.5% (1999-2001) to 16% (2002-2003) and this was associated with a significant decline of a circulating 19F penicillin-resistant S. pneumoniae serotype (from 89% to 26%), respectively. CONCLUSIONS: S. pneumoniae and H. influenzae are the 2 most common pathogens producing otitis media in Costa Rican children. An increase in the number of H. influenzae and M. catarrhalis was observed in recent years. Penicillin-nonsusceptible S. pneumoniae isolates were more commonly observed during the rainy season, in which increased morbidity with respiratory pathogens is observed.     

Upper respiratory tract bacterial carriage in Aboriginal and non-Aboriginal children in a semi-arid area of Western Australia

BACKGROUND: Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are associated with otitis media (OM). Indigenous children experience particularly high rates of OM. Few studies worldwide have described upper respiratory tract (URT) carriage in Indigenous and non-Indigenous children living in the same area. AIM: The aim of this study was to describe URT bacterial carriage in Aboriginal and non-Aboriginal children in the Kalgoorlie-Boulder area, Western Australia, as part of an investigation into causal pathways to OM. METHODS: Five hundred four and 1045 nasopharyngeal aspirates were collected from 100 Aboriginal and 180 non-Aboriginal children, respectively, followed from birth to age 2 years. Standard procedures were used to identify bacteria. RESULTS: Overall carriage rates of S. pneumoniae, M. catarrhalis and H. influenzae in Aboriginal children were 49%, 50% and 41%, respectively, and 25%, 25% and 11% in non-Aboriginal children. By age 2 months S. pneumoniae and M. catarrhalis had been isolated from 37% and 36% of Aboriginal children and from 11% and 12% of non-Aboriginal children, respectively. From age 3 months onward, carriage rates in Aboriginal children were 51% to 67% for S. pneumoniae and M. catarrhalis and 42% to 62% for H. influenzae; corresponding figures for non-Aboriginal children were 26% to 37% for S. pneumoniae and M. catarrhalis and 11% to 18% for H. influenzae. Non-Aboriginal children had higher carriage rates in winter than in summer, but season had little effect in Aboriginal children. Staphylococcus aureus carriage was highest under age 1 month (55% Aboriginal, 61% non-Aboriginal) and was always higher in non-Aboriginal than Aboriginal children. CONCLUSIONS: Interventions are needed to reduce high transmission and carriage rates, particularly in Aboriginal communities, to avoid the serious consequences of OM.     

Bacteriologic and clinical efficacy of high dose amoxicillin for therapy of acute otitis media in children

BACKGROUND: High dose (70 to 90 mg/kg/day) amoxicillin is recommended as first line therapy of acute otitis media (AOM) in geographic areas where drug-resistant Streptococcus pneumoniae is prevalent. Information on the bacteriologic efficacy of high dose amoxicillin treatment for AOM is limited. OBJECTIVES: To evaluate the bacteriologic and clinical efficacy of high dose amoxicillin as first line therapy in AOM. METHODS: In a prospective study 50 culture-positive patients ages 3 to 22 months (median, 9 months; 77% <1 year) were treated with high dose amoxicillin (80 mg/kg/day three times a day for 10 days) No antibiotics were administered 72 h before enrollment. Twenty-four (48%) patients presented with their first episode of AOM. Middle ear fluid was cultured by tympanocentesis at enrollment and on Days 4 to 6 of therapy. Additional middle ear fluid cultures were obtained if clinical relapse occurred. Bacteriologic failure was defined by positive cultures on Days 4 to 6 and clinical failure by no change or worsening of AOM signs and symptoms and requirement for additional antibiotics during therapy and/or at end of therapy. Patients were followed until Day 28 +/- 2. Susceptibility to penicillin and amoxicillin was measured by E-test. RESULTS: Sixty-five organisms were recovered at enrollment: Haemophilus influenzae (38), Streptococcus pneumoniae (24), Streptococcus pyogenes (2) and Moraxella catarrhalis (1). Eighteen (75%) S. pneumoniae were nonsusceptible to penicillin (MIC > 0.1 microg/ml). All 24 S. pneumoniae isolates had amoxicillin MIC < or = 2.0 microg/ml. Thirteen (34%) of the 38 H. influenzae were beta-lactamase producers. Eradication was achieved in 41 (82%) patients for 54 of 65 (83%) pathogens: 22 of 24 (92%) S. pneumoniae, 21 of 25 (84%) beta-lactamase-negative H. influenzae, 8 of 13 (62%) beta-lactamase-positive H. influenzae, 2 of 2 S. pyogenes and 1 of 1 M. catarrhalis. Seven organisms not initially present were isolated on Days 4 to 6 in 5 patients: 3 beta-lactamase-positive H. influenzae; 1 beta-lactamase-negative H. influenzae; 2 S. pneumoniae; and 1 M. catarrhalis. In total 14 of 50 (28%) patients failed bacteriologically on Days 4 to 6 (persistence + new infection), of whom 9 (64%) had beta-lactamase-positive H. influenzae. Three (33%) of the 9 patients with bacteriologic failure (2 beta-lactamase-positive H. influenzae, 1 S. pneumoniae) failed also clinically on Days 4 to 6. CONCLUSIONS: The predominant pathogens isolated from children with AOM failing high dose amoxicillin therapy were beta-lactamase-producing organisms. Because its overall clinical efficacy is good, high dose amoxicillin is still an appropriate choice as first line empiric therapy for AOM, followed by a beta-lactamase-stable drug in the event of failure.     

Changes in nasopharyngeal flora during otitis media of childhood

The nasopharyngeal flora of healthy children were compared with flora in children with otitis media caused by nontypable Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Forty healthy children were followed prospectively and compared with 70 children with 43 episodes of nontypable H. influenzae, 21 episodes of S. pneumoniae and 28 episodes of M. catarrhalis otitis media. Carriage of nontypable H. influenzae (95% vs. 65%, P less than 0.001), S. pneumoniae (91% vs. 52%, P less than 0.005) and M. catarrhalis (86% vs. 52%, P less than 0.001) increased significantly during episodes of otitis media compared with healthy periods. The quantity of nontypable H. influenzae, S. pneumoniae and M. catarrhalis in nasopharyngeal secretions also increased during active infection compared with healthy periods: 3.0 vs. 2.0, P less than 0.005; 3.2 vs. 2.1, P less than 0.001; and 3.3 vs. 2.5, P less than 0.01, respectively. At the same time, nonpathogens of the resident flora, in particular viridans streptococci, declined in carriage: 65% vs. 22%, P less than 0.001. These data suggest that respiratory pathogens become relatively more important in the microenvironment of the nasopharynx during episodes of otitis media. Furthermore the absence of a middle ear pathogen in a nasopharyngeal culture strongly suggests that the pathogen is not present in the middle ear space (negative predictive value greater than 0.96).     

Bacteriologic and clinical efficacy of oral gatifloxacin for the treatment of recurrent/nonresponsive acute otitis media: an open label, noncomparative, double tympanocentesis study

BACKGROUND: Gatifloxacin is an 8-methoxyfluoroquinolone with good activity against respiratory pathogens. OBJECTIVES: To document the bacteriologic and clinical efficacy of gatifloxacin in recurrent/nonresponsive acute otitis media (AOM). METHODS: One hundred sixty patients 6 to 48 months of age with recurrent/nonresponsive AOM received gatifloxacin suspension (10 mg/kg once daily for 10 days). Recurrent AOM was defined as > or =3 AOM episodes during the previous 6 months or > or =4 AOM episodes during the previous 12 months. Nonresponsive AOM was defined as AOM occurring < or =14 days after completing antibiotic treatment or not improving after > or =48 h of therapy. Middle ear fluid (MEF) obtained by tympanocentesis pretreatment (Day 1) and 3 to 5 days after initiation of treatment (Days 4 to 6) was cultured. Additional MEF cultures were obtained if clinical failure or recurrence of AOM occurred. Bacteriologic failure was defined by culture-positive MEF during treatment. Patients were followed until Days 22 to 28. Susceptibility was determined by broth microdilution. RESULTS: One hundred twenty-eight (80%) patients completed treatment, and 32 discontinued the study prematurely (adverse events, 17; lost to follow-up, 10; consent withdrawal, 3; and laboratory abnormalities, 2). From 89 patients (median age, 1 year; median number of prior AOM episodes, 4; range, 0 to 12), 121 pathogens were recovered: Haemophilus influenzae, 74 (61%); Streptococcus pneumoniae, 36 (30%); Moraxella catarrhalis, 9 (7%); and Streptococcus pyogenes, 2 (2%). The 36 S. pneumoniae isolates were susceptible to gatifloxacin (MIC50 0.25 microg/ml); 26 of 36 (72%) were penicillin-nonsusceptible (15 fully resistant). All 74 H. influenzae isolates were susceptible to gatifloxacin (MIC < or = 0.03 mg/ml). Fourteen of 74 (19%) and 9 of 9 (100%) H. influenzae and M. catarrhalis isolates, respectively, produced beta-lactamase. Bacteriologic eradication was achieved for 118 of 121 (98%) pathogens: 74 of 74 H. influenzae; 34 of 36 (94%) S. pneumoniae; 9 of 9 M. catarrhalis; and 1 of 2 S. pyogenes. Clinical improvement/cure at end of treatment was seen in 103 of 114 (90%) clinically evaluable patients. Clinical recurrence of AOM after completion of therapy occurred in 31 patients. Of the 27 recurrent AOM cases in which tympanocentesis was performed, there were 16 (59%) new infections, 4 (15%) culture-negative results and only 7 (26%) true bacteriologic relapses. Adverse events were recorded in 21 of 160 (13%) patients: vomiting, 16; diarrhea, 3; maculopapular rash, 2. No articular adverse events were recorded. CONCLUSION: Gatifloxacin is efficacious and safe for the treatment of recurrent/nonresponsive AOM.