Beta-lactamase producing Haemophili occurrence in clinical materials and carriage in healthy children

Beta-lactamase production was investigated in 126 H. influenzae and 15 H. parainfluenzae strains isolated in various infections. In H. influenzae the rate of beta-lactamase positive strains was 5.6%, in non-encapsulated strains it was higher (9.7%) than in capsule bearing strains (3.1%). Among beta-lactamase producing H. influenzae strains biotype II was predominant, whereas biotype I prevailed in beta-lactamase positive strains of H. parainfluenzae. A study undertaken in 101 children of a day-care nursery revealed 16.8% carriers of beta-lactamase producing Haemophili. Among the isolated strains we found the double number of H. parainfluenzae than H. influenzae strains showing beta-lactamase activity. This result supports the hypothesis of H. parainfluenzae being the reservoir of resistances plasmids in Haemophili.     

Nosopharyngeal microflora in ambulatory treated children and adults with upper respiratory tract infections

Upper respiratory tract consists resident and transient bacterial microflora, which in appropriate condition can cause infection. Bacteriological study was performed among 201 patients with upper respiratory tract infections treated in ambulatory. From nasal and pharyngeal swabs Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Streptococci group A, B, C, G were isolated. Antibiotic susceptibility testing of isolated strains was performed using CLSI criteria. All isolated strains of streptococci were susceptible to penicillin; some of them demonstrated resistance to macrolides and lincosamides. Few isolated strains of H. influenzae demonstrated resistance to penicillin and cotrimoxazole. Azitromycin resistant strains were not detected. All isolated strains of M. catarrhalis were beta-lactamase positive and demonstrated resistance to penicillin. Strains of methicillin sensitive S. aureus (MSSA) were isolated most frequently from pharyngeal swabs (35.4%) and S. pneumoniae (33.3)--from nasal swabs.     

Antibiotic resistance in Streptococcus pneumoniae and Haemophilus influenzae. Report of a study group on bacterial resistance.

Twenty laboratories in England and Scotland took part in 1977 in a survey of antibiotic resistance in Streptococcus pneumoniae and Haemophilus influenzae. In Str pneumoniae 59 (6.8%) of the 866 strains studied were resistant to tetracycline and three to chloramphenicol, and one strain showed a decreased susceptibility to penicillin. The prevalence of resistance to tetracycline was lower than that found in a similar study performed in 1975. Nine hundred and fifty-two strains of H influenzae were examined: 15 (1.6%) were resistant to ampicillin (all were beta-lactamase producers) and 26 (2.7%) to tetracycline. Only two strains were resistant to chloramphenicol and two to trimethoprim. Sixty-three H influenzae strains were capsulated. Thirty-four of these were of Pittman type b, and antibiotic resistance, particularly to ampicillin, was more common in these than in other serotypes or non-typable strains. Some variation was seen in the resistance rate of both H influenzae and Str pneumoniae to tetracycline in strains from different centres, but too few were isolated to assess whether this represented a true geographical difference.     

Moraxella catarrhalis in chronic and relapsing respiratory tract infections in children]

Examination of 700 children with chronic and relapsing respiratory tract infections showed that during the period from 1996 to 2003 Moraxella catarrhalis strains were isolated from the sputum of 5.5-9.7% of the patients. The frequency of the emergence was the third after Haemophilus influenzae and Streptococcus pneumoniae. In healthy children M. catarrhalis was isolated in 2.7% of the cases. The most frequent detection of M. catarrhalis was stated in children under 1 year (4.5%). The antibiotic susceptibility tests revealed that the majority of the M. catarrhalis isolates had beta-lactamase activity, were resistant to benzylpenicillin, ampicillin and lincomycin and highly susceptible to amoxycillin/clavulanate, macrolides, certain cephalosporins and levofloxacin. The isolates were most frequent in the patients of the rather severe contingent (congenital lung disease, alveolitis, chronic pneumonia, bronchial asthma). In such patients the bronchoobstructive syndrome was more frequent (46.6%). High frequency of the affection of the upper respiratory tracts in the examined children was stated (62.1%).     

深圳市儿童社区获得性肺炎细菌病原学及其耐药性

目的研究儿童社区获得性肺炎细菌病原学及其耐药性特征,指导临床合理应用抗菌药物。方法对2006年2月至2007年3月1年期间住院的5岁及5岁以下社区获得性肺炎病人,进行深部呼吸道吸引物细菌培养,并且检测分离菌株对常用抗菌药物的耐药性。结果1441例病人中,722例检出细菌共761株,分离阳性率为50．1％,分离菌依次为肺炎克雷伯菌170株（22．3％）、大肠埃希菌130株（17．1％）、肺炎链球菌89株（11．7％）、金黄色葡萄球菌63株（8．3％）及流感和副流感嗜血杆菌60株（7．9％）。耐甲氧西林金黄色葡萄球菌（MRSA）检出率为15．9％;对青霉素不敏感的肺炎链球菌（包括PISP和PRSP）检出率为84．3％;肺炎克雷伯菌、大肠埃希菌、粘质沙雷菌和阴沟肠杆菌产ESBLs的检出率分别为31．2％、46．2％、94．8％和16．8％;流感嗜血杆菌和副流感嗜血杆菌对氨苄西林的耐药率为36％和40％;铜绿假单胞菌和鲍曼复合不动杆菌对亚胺培南的耐药率分别为10．7％和13．2％。结论在深圳儿童社区获得性肺炎的分离菌中,革兰阴性菌明显多于革兰阳性菌,分离菌依次为肺炎克雷伯菌、大肠埃希菌、肺炎链球菌、金黄色葡萄球菌及流感和副流感嗜血杆菌。分离细菌对常用抗菌药物的耐药性较为严重。     

Etiology of pulmonary diseases in children in Khabarovsk Region

Microflora of upper respiratory tract in 658 children aged 1 month - 17 years hospitalized with acute pneumonia (AP), acute bronchitis (AB), recurrent obstructive bronchitis (ROB), malformation of lungs (ML) and broncho-alveolar dysplasia (BALD) were studied. Carriage rates of Streptococcus pneumoniae (up to 95%) and Haemophilus influenzae (up to 89%) in 240 children attending daycare centers and schools were determined. Etiology of infectious process was ascertained in 40% of cases. S. pneumoniae was isolated in 45% of acute cases (AP and AB) and in 25% of chronic cases (BALD). H. influenzae was isolated in 8 - 12% of acute cases and in 32% of chronic cases. In 23 - 29% of all cases of pulmonary pathology in children persistence of Enterococcus faecium was determined. There were 13 different serotypes among isolated pneumococci. In patients with pneumonia the rate of detection of S. pneumoniae and H. influenzae DNA fragments by PCR was significantly higher compared with rate of their isolation from sputum.     

Comparative characteristics of the Haemophilus influenzae strains isolated from healthy children and from patients with acute and chronic bronchopulmonary diseases

The comparative biochemical and serological characterization of 424 H. influenzae strains isolated from healthy children and patients with acute and chronic bronchopulmonary diseases is presented. As the result of biotyping H. influenzae strains, 82.3-90.9% of the strains isolated from both healthy children and patients with acute and chronic bronchopulmonary diseases were found to belong to the first three biotypes according to M. Kilian's classification. Among H. influenzae strains isolated from healthy children no capsular variants were detected in the coagglutination test. From patients with acute and chronic diseases of respiratory organs, as a rule, the capsular variants of H. influenzae were isolated (94.4% and 98.1%, respectively). In patients with chronic pneumonia biotypes I, II and III, more seldom biotype V, proved to be mo st invasive. In the determination of the minimum inhibiting concentration of ampicillin, no H. influenzae strains resistant to this antibiotic were detected.     

Microbiological control of drug resistance of causative agents in suppurative-septic infections in newborn infants

Resistance of the main causative agents of purulent septic infections such as pneumonia, meningitis, sepsis, etc. to 11 chemotherapeutic drugs was studied. The pathogens were isolated from autopsies of 203 newborns who died within 1981 to 1987. Among 2978 isolates belonging to Enterobacteriaceae (2466 strains) and Pseudomonadaceae (512 strains) which constituted 88% of all the isolates, strains with multiple resistance predominated: 90% of the strains resistant to 4 or more antibiotics, 77% of the strains resistant to 6 or more antibiotics and 48% of the strains resistant to 8 or more antibiotics. The highest number of the isolates were resistant to 8 and 9 chemotherapeutics (19 and 20%, respectively). 84% of all the isolates belonged to 4 genera: Klebsiella (34%), Escherichia (21%), Serratia (14%) and Pseudomonas (15%). They were characterized by the highest resistance spectra. In all the cases massive colonization of the intestine by the strains with multiple resistance which caused purulent septic infections was observed. The most frequent variants of the drug resistance combination were determined. In the total frequency of the isolate with multiple resistance no significant differences were detected in 1981 and thereafter. In 1986-1987 the frequency of S. marcescens strains increased 3-5 times with simultaneous broadening of their drug resistance spectra. Strains of S. marcescens and K. pneumoniae with multiple drug resistance endemic for definite hospitals were detected.     

Haemophilus influenzae antibiotic resistant strains isolated in Moscow in 2002-2004]

The results of 3-year observation on emergence of H. influenzae antibiotic resistant strains in Moscow are summarized. The study included 566 strains isolated from patients in 2002-2004. The susceptibility was determined by the 2-fold microdilution method on the Haemophilus test medium. The percentage of the resistant strains isolated in 2002, 2003 and 2004 was the following: ampicillin --4.9, 3.2 and 3.6%, tetracycline--3.3, 3.2 and 1.8% and co-trimoxazole--10.9, 20.9 and 20% respectively. The strains isolated in 2003 and 2004 were resistant to azithromycin in 0.6 and 1.8% of the isolates and to clarithromycin in 1.3 and 3.2% of the isolates respectively. Five isolates differed by the minimum resistance to ampicillin whereas producing no beta-lactamase (BLNAR strains). The drugs of choice for the treatment of respiratory tract infections mainly due to H. influenzae, i.e. acute otitis and sinusitis, chronic bronchitis exacerbation and sometimes pneumonia remain betalactam antibiotics. From the microbiological viewpoint the inhibitor-protected aminopenicillins, cefuroxime and cefotaxime have no significant advantages vs. amoxycillin. The use of cotrimoxazole and chloramphenicol should be considered inexpedient.     

Problems of prevalance and resistance of nosocomial Klebsiella pneumonia in hospitals of Russia]

Prevalence of Klebsiella pneumoniae among gramnegative pathogens of nosocomial infections in intensive care units of 33 hospitals of 22 towns in Russia was investigated. Antibiotic susceptibility and extended-spectrum beta-lactamase production were tested in 420 nosocomial K. pneumoniae isolates. Carbapenems (imipenem, meropenem and ertapenem) showed the highest activity. Extended-spectrum beta-lactamase production based on the phenotyping methods was revealed in 342 (81.4%) isolates. The maximum activity against the K. pneumoniae isolates producing extended-spectrum beta-lactamase was observed in imipenem and meropenem (no unsusceptible strains were isolated). 3.2% of the isolates was not susceptible to ertapenem. Differences in the activity of cefoperazone/sulbactam, amikacin, ciprofloxacin and levofloxacin against the extended-spectrum beta-lactamase producing isolates in various hospitals were recorded.     

Molecular characterization of a small Haemophilus influenzae plasmid specifying beta-lactamase and its relationship to R factors from Neisseria gonorrhoeae.

The ampicillin-resistant Haemophilus influenzae strain Ve445 which caused purulent meningitis and septicaemia in a newborn child in Germany contained a 4.4 megadalton (Mdal) plasmid (pVe445) and produced a TEM type beta-lactamase. The transformation to ampicillin resistance of a sensitive Escherichia coli strain with isolated pVe445 DNA proved that the structural gene for the beta-lactamase resided on this plasmid genome. Molecular DNA-DNA hybridization studies and electron microscope DNA heteroduplex analysis indicated that pVe445 probably contained 38 to 41% of the ampicillin translocation DNA segment (TnA) found on R factors of enteric origin. The TnA fragment present in pVe445 most likely does not contain both of the inverted repeat sequences of TnA. DNA-DNA polynucleotide sequence studies indicated that the 4.4 Mdal plasmid pVe445 was unrelated to the 30 to 38 Mdal H. influenzae R plasmids but was closely related to the 4.1 Mdal ampicillin resistance specifying H. influenzae plasmid RSF0885 isolated in the U.S.A. The H. influenzae plasmid pVe445 shared 91% of its base sequences with the beta-lactamase specifying Neisseria gonorrhoeae plasmid pMR0360 (4.4 Mdal) and had 85% of its base sequences in common with the beta-lactamase specifying N. gonorrhoeae plasmid pMR0200 (3.2 Mdal). All of the four 3.2 to 4.4 Mdal beta-lactamase specifying R plasmids of H. influenzae and N. gonorrhoeae investigated probably have a common evolutionary origin.     

Evaluation of the influence of the bacterial vaccines Pneumo-23 and Act-HIB on the course of the chronic inflammatory process of the respiratory organs in children

The effectiveness and safety of vaccination of children having chronic inflammatory lung diseses with Pneumo-23 and Act-HIB were evaluated. The group under study included 38 children having chronic pneumonia, congenital defects of lung development, Kartagener's syndrome, mucoviscidosis; of these children, 25 were vaccinated with Pneumo-23 and 13--with Act-HIB. For comparison a group of 40 children with the same pathology, but not vaccinated, was used. A favorable course of the postvaccinal period was noted. Prior to vaccination Streptococcus pneumoniae in association with Haemophilus influenzae were isolated from all patients; in a year after vaccination with Pneumo-23 these microorganisms were isolated only in monoculture: S. pneumoniae in 3 out of 25 cases (88% elimination) and H. influenzae in 10 out of 25 cases (60% elimination).     

Etiology of acute and chronic bronchopulmonary diseases in children. II. A study of the specific immune response by counterimmunoelectrophoresis and the complement fixation and passive hemagglutination reactions

Specific immune response to Streptococcus pneumoniae and Haemophilus influenzae has been studied in 158 children with acute pneumonia and pleuritis and 128 children with chronic pneumonia by countercurrent immunoelectrophoresis (CIE) and in the complement fixation (CFT) and passive hemagglutination (PHA) tests. The use of CIE leads to the detection of antibodies to H. influenzae in 23.7% of children with acute pneumonia and in 46.9% of children with chronic pneumonia. In the CFT antibodies to H. influenzae are also more often detected in children with chronic pneumonia (48%) than in those with acute respiratory infections (12.2%). In the PHA test high titers of antibodies to type b H. influenzae capsular polysaccharide occur in 11.9% of children with acute pneumonia and in 8.2% of children with chronic pneumonia.     

Antibiotic susceptibility and molecular mechanisms of cephalosporins resistance in Klebsiella isolates from patients with hospital-acquired infections]

Antibiotic susceptibility of nosocomial Klebsiella isolates from inpatients of 30 medical centres in 15 various regions of Russia was studied. In total 212 strains were tested. The Klebsiella genus was represented by the following species: Klebsiella pmeumoniae ss. pneumoniae (182 isolates, 85.8%), Klebsiella pneumonia ss. ozaenae (1 isolate, 0.5%), Klebsiella oxytoca (29 isolates, 13.7%). The susceptibility was determined by the broth microdilution method. Carbapenems (imipenem and meropenem) remained to be the most active antibacterial agents. However, 1 imipenem resistant strain and 2 meropenem resistant strains were isolated. As for the 3rd generation cephalosporins, the lowest MICs were observed with the use of the inhibitor-protected agents, such as ceftazidime/clavulanic acid (MIC50 0.25 mcg/ml, MIC90 64 mcg/ml). 48.8%, 16.9%, 29.7% and only 10.5% of the isolates was susceptible to cefepime, cefotaxime, ceftazidime and cefoperazone respectively. Detecting of the beta-lactamase genes (TEM, SHV and CTX) was performed by PCR in 42 strains of Klebsiella pneumoniae ss. pneumoniae. Alone or in various combination the TEM type beta-lactamases were detected in 16 (38.1%) isolates. SHV and CTX were detected in 29 (69%) and 27 (64.3%) isolates respectively. Combinations of 2 and 3 different determinants of resistance to beta-lactams were revealed in 23.8% and 26.2% of the isolates respectively. No isolates producing class B MBL among the carbapenem resistant nosocomial Klebsiella strains were detected.     

Synthesis and antibacterial activity of HMR 3647 a new ketolide highly potent against erythromycin-resistant and susceptible pathogens

In the search for new ketolides with improved activities against erythromycin-resistant S. pneumoniae and H. influenzae we synthesized a new 11,12 carbamate ketolide substituted by an imidazo-pyridyl side chain: HMR 3647. This compound demonstrated a potent activity against erythromycin susceptible and resistant pathogens, including penicillin G/erythromycin A-resistant S. pneumoniae and H. influenzae. In vivo, HMR 3647 displayed good pharmacokinetic parameters (Cmax = 2.9 microg/ml, bioavailability=49%, AUC0.8 = 17.2 microg.h/l, t1/2=1h) and was shown to have a high therapeutic efficacy in mice infected by various respiratory pathogens, including multi-resistant S. pneumoniae and Gram negative bacteria such as H. influenzae. HMR 3647 appears to be a very promising agent for the treatment of respiratory infections and is currently in clinical trials.     

Prediction of the pathogens that are the cause of pneumonia by the battlefield hypothesis

Commensal organisms are frequent causes of pneumonia. However, the detection of these organisms in the airway does not mean that they are the causative pathogens; they may exist merely as colonizers. In up to 50% cases of pneumonia, the causative pathogens remain unidentified, thereby hampering targeting therapies. In speculating on the role of a commensal organism in pneumonia, we devised the battlefield hypothesis. In the "pneumonia battlefield," the organism-to-human cell number ratio may be an index for the pathogenic role of the organism. Using real-time PCR reactions for sputum samples, we tested whether the hypothesis predicts the results of bacteriological clinical tests for 4 representative commensal organisms: Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas spp., and Moraxella catarrhalis. The cutoff value for the organism-to-human cell number ratio, above which the pathogenic role of the organism was suspected, was set up for each organism using 224 sputum samples. The validity of the cutoff value was then tested in a prospective study that included 153 samples; the samples were classified into 3 groups, and each group contained 93%, 7%, and 0% of the samples from pneumonia, in which the pathogenic role of Streptococcus pneumoniae was suggested by the clinical tests. The results for Haemophilus influenzae, Pseudomonas spp., and Moraxella catarrhalis were 100%, 0%, and 0%, respectively. The battlefield hypothesis enabled legitimate interpretation of the PCR results and predicted pneumonia in which the pathogenic role of the organism was suggested by the clinical test. The PCR reactions based on the battlefield hypothesis may help to promote targeted therapies for pneumonia. The prospective observatory study described in the current report had been registered to the University Hospital Medical Information Network (UMIN) registry before its initiation, where the UMIN is a registry approved by the International Committee of Medical Journal Editors (ICMJE). The UMIN registry number was UMIN000001118: A prospective study for the investigation of the validity of cutoff values established for the HIRA-TAN system (April 9, 2008).     

The effect of human immunodeficiency virus infection on the distribution and outcome of pneumonia in intensive care units.

To determine the frequency and distribution of pneumonia in an intensive care unit (ICU), we retrospectively examined the records of 1,854 consecutive ICU admissions between January 1987 and April 1990. A total of 266 patients met criteria for pneumonia (unilateral or bilateral infiltrate by chest roentgenogram, plus 2 of the following: leukocyte count > 10 x 10(9) per liter, temperature > 38.5 degrees C, or culture of blood or sputum positive for pathogens). Pneumocystis carinii pneumonia in patients infected with the human immunodeficiency virus was the most frequent cause (28%) precipitating an ICU admission in this series of patients. Streptococcus pneumoniae (13%), Staphylococcus aureus (8%), Haemophilus influenzae (4%), and viruses (4%) were also commonly observed. Overall mortality was 20%. An APACHE II score of greater than 24, the need for intubation, and the presence of P carinii were predictive of increased mortality. Age, sex, and length of stay did not predict final results. Patients with P carinii pneumonia who required intubation had an overall mortality of 54%, which was higher than patients without P carinii pneumonia who required intubation (P < .05). Our experience shows the changing spectrum of pneumonia in ICUs. In contrast to reports of a decade ago in which S pneumoniae and Pseudomonas aeruginosa are cited as most common, P carinii is now most prevalent in our ICU. Although our findings reflect the increasing incidence of human immunodeficiency virus infection in San Francisco, California, they may also be pertinent to other areas in the United States where the incidence of this infection continues to increase.     

新生儿院内获得性肺炎患者病原体特征及 危险因素分析

目的分析院内新生儿获得性肺炎患者病原体分布、药敏情况和相关危险因素,并探讨其临床意义。方法收集2015年10月至2017年4月于我院接受治疗的100例院内获得性肺炎新生儿为观察组。选择同期于我院出生的未发生院内获得性肺炎的新生儿100例为对照组。采集观察组患儿下呼吸道分泌物,利用全自动微生物分析仪进行菌株种类和数量鉴定,利用K-B纸片扩散法进行药敏试验。对院内获得性肺炎的危险因素进行单因素回归分析。结果 100例院内获得性肺炎新生儿下呼吸道分泌物共检测出病原微生物168株,其中细菌135株(80.36%),病毒30株(17.86%),真菌3株(1.78%)。细菌中革兰阴性菌116株(69.05%),以大肠埃希菌(49株,29.17%)及肺炎克雷伯菌(42株,25.00%)为主;革兰阳性菌19株(11.31%),以金黄色葡萄球菌(10株,5.95%)为主。病毒以呼吸道合胞病毒(23株,13.69%)为主。大肠埃希菌及肺炎克雷伯菌均对常用抗生素具有极高的耐药性,包括氨苄西林、头孢哌酮、头孢曲松及头孢唑林等;对氨基糖苷类、喹诺酮类、碳青霉烯类抗生素高度敏感。新生儿的住院天数、分娩方式及吸痰均与院内获得性肺炎的发生有密切联系,差异均有统计学意义(P0.05)。结论新生儿院内获得性肺炎的致病菌以革兰阴性菌为主,临床治疗时可适当选用氨基糖苷类、喹诺酮类、碳青霉烯类抗生素。住院天数、剖腹产及吸痰均为新生儿院内获得性肺炎的危险因素,应加强对上述危险因素的保护。     

Upper respiratory tract microbial communities, acute otitis media pathogens, and antibiotic use in healthy and sick children

The composition of the upper respiratory tract microbial community may influence the risk for colonization by the acute otitis media (AOM) pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. We used culture-independent methods to describe upper respiratory tract microbial communities in healthy children and children with upper respiratory tract infection with and without concurrent AOM. Nasal swabs and data were collected in a cross-sectional study of 240 children between 6 months and 3 years of age. Swabs were cultured for S. pneumoniae, and real-time PCR was used to identify S. pneumoniae, H. influenzae, and M. catarrhalis. The V1-V2 16S rRNA gene regions were sequenced using 454 pyrosequencing. Microbial communities were described using a taxon-based approach. Colonization by S. pneumoniae, H. influenzae, and M. catarrhalis was associated with lower levels of diversity in upper respiratory tract flora. We identified commensal taxa that were negatively associated with colonization by each AOM bacterial pathogen and with AOM. The balance of these relationships differed according to the colonizing AOM pathogen and history of antibiotic use. Children with antibiotic use in the past 6 months and a greater abundance of taxa, including Lactococcus and Propionibacterium, were less likely to have AOM than healthy children (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25 to 0.85). Children with no antibiotic use in the past 6 months, a low abundance of Streptococcus and Haemophilus, and a high abundance of Corynebacterium and Dolosigranulum were less likely to have AOM (OR, 0.51; 95% CI, 0.31 to 0.83). An increased understanding of polymicrobial interactions will facilitate the development of effective AOM prevention strategies.     

Infectious exacerbations of chronic obstructive pulmonary disease associated with respiratory viruses and non-typeable Haemophilus influenzae

Infectious exacerbations of chronic obstructive pulmonary disease (COPD) have been reported to occur with both viral and bacterial pathogens. In this study, 35 exacerbations associated with the isolation of non-typeable Haemophilus influenzae from sputum were identified as part of a prospective longitudinal study. Samples from these patients were subjected to immunoassays to identify a new immune response to the homologous isolate of non-typeable H. influenzae to more accurately assess a bacterial etiology. These patients also were studied carefully for evidence of viral infection using viral culture, serology and polymerase chain reaction-based assays. Sixteen of 35 exacerbations (45.7%) were associated with evidence of acute viral infection and 11 of the 35 exacerbations (31.4%) were associated with the development of new serum IgG to homologous non-typeable H. influenzae. Overall, evidence of infection with a respiratory virus or non-typeable H. influenzae was seen in 24 of 35 exacerbations (68.6%). No association between viral infection and immune response to non-typeable H. influenzae was observed, although a trend toward an immune response to non-typeable H. influenzae and absence of viral infection was seen. The results show that exacerbations in adults with COPD were associated with infection caused by virus alone, non-typeable H. influenzae alone, or virus and non-typeable H. influenzae simultaneously.