Invasive Haemophilus influenzae in British Columbia: non-Hib and non-typeable strains causing disease in children and adults

Shuel, Michelle; Hoang, Linda; Law, Dennis K. S.; Tsang, Raymond S. W.

doi:10.1016/j.ijid.2010.10.005

Cited by 47 publications

(60 citation statements)

References 29 publications

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“…Routine use of the Hib vaccine has changed the epidemiology of H. influenzae, and unencapsulated H. influenzae now accounts for most invasive infections, followed by serotypes f and b (224)(225)(226)(227)(228)(229). An unexpectedly large proportion of invasive childhood infections caused by serotype a was recently reported from several Canadian provinces (205,230) and among Alaska Native children (231). There is no evidence of substantial replacement disease with non-b serotypes in young children in the United States (232) or of increases of non-b infection in Australian indigenous children (233).…”

Section: Haemophilus Influenzae In the Post-hib-vaccine Eramentioning

confidence: 99%

Classification, Identification, and Clinical Significance of Haemophilus and Aggregatibacter Species with Host Specificity for Humans

2014

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SUMMARY The aim of this review is to provide a comprehensive update on the current classification and identification of Haemophilus and Aggregatibacter species with exclusive or predominant host specificity for humans. Haemophilus influenzae and some of the other Haemophilus species are commonly encountered in the clinical microbiology laboratory and demonstrate a wide range of pathogenicity, from life-threatening invasive disease to respiratory infections to a nonpathogenic, commensal lifestyle. New species of Haemophilus have been described ( Haemophilus pittmaniae and Haemophilus sputorum ), and the new genus Aggregatibacter was created to accommodate some former Haemophilus and Actinobacillus species ( Aggregatibacter aphrophilus , Aggregatibacter segnis , and Aggregatibacter actinomycetemcomitans ). Aggregatibacter species are now a dominant etiology of infective endocarditis caused by fastidious organisms (HACEK endocarditis), and A. aphrophilus has emerged as an important cause of brain abscesses. Correct identification of Haemophilus and Aggregatibacter species based on phenotypic characterization can be challenging. It has become clear that 15 to 20% of presumptive H. influenzae isolates from the respiratory tracts of healthy individuals do not belong to this species but represent nonhemolytic variants of Haemophilus haemolyticus . Due to the limited pathogenicity of H. haemolyticus , the proportion of misidentified strains may be lower in clinical samples, but even among invasive strains, a misidentification rate of 0.5 to 2% can be found. Several methods have been investigated for differentiation of H. influenzae from its less pathogenic relatives, but a simple method for reliable discrimination is not available. With the implementation of identification by matrix-assisted laser desorption ionization–time of flight mass spectrometry, the more rarely encountered species of Haemophilus and Aggregatibacter will increasingly be identified in clinical microbiology practice. However, identification of some strains will still be problematic, necessitating DNA sequencing of multiple housekeeping gene fragments or full-length 16S rRNA genes.

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Section: Haemophilus Influenzae In the Post-hib-vaccine Eramentioning

confidence: 99%

Classification, Identification, and Clinical Significance of Haemophilus and Aggregatibacter Species with Host Specificity for Humans

2014

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“…aemophilus influenzae is one of the normal inhabitants of the human nasopharynx and is responsible for pneumonia, acute otitis media (AOM), and acute rhinosinusitis (1)(2)(3). The presence or absence of a polysaccharide capsule segregates this bacterial species into two well-defined groups: one group of encapsulated strains and another group of noncapsulated strains, commonly referred to as nontypeable H. influenzae (NTHi) (3).…”

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confidence: 99%

“…The presence or absence of a polysaccharide capsule segregates this bacterial species into two well-defined groups: one group of encapsulated strains and another group of noncapsulated strains, commonly referred to as nontypeable H. influenzae (NTHi) (3). Common infections caused by NTHi include otitis media in children and lower airway infections of chronic obstructive pulmonary disease in adults (4,5).…”

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confidence: 99%

Serum Concentrations of Antibodies against Outer Membrane Protein P6, Protein D, and T- and B-Cell Combined Antigenic Epitopes of Nontypeable Haemophilus influenzae in Children and Adults of Different Ages

Chen

Shang

et al. 2016

Clin Vaccine Immunol

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e Nontypeable Haemophilus influenzae (NTHi) is one of the most common etiologies of acute otitis media, rhinosinusitis, and pneumonia. Outer membrane proteins (OMPs) are the main focus in new vaccine development against NTHi, as the H. influenzae type b (Hib) vaccine does not cover noncapsulated NTHi. The OMPs P6 and protein D are the most promising candidate antigens for an NTHi vaccine, and low antibody levels against them in serum may be correlated with infection caused by NTHi. In the current study, we measured the antibody titers against P6, protein D, and their T-and B-cell combined peptide epitopes in healthy individuals of different ages. We found that children <1 month old had the lowest antibody levels against NTHi P6, protein D, and their T-and B-cell combined antigenic epitopes. Antibody titers increased at ages 1 to 6 months, peaked at 7 months to 3 years, and remained high at 4 to 6 years. The antibody titers started to decrease after 6 years and were the lowest in the 21-to 30-year group. The geometric mean titers (GMTs) of T-and B-cell combined antigenic epitopes in P6 and protein D were positively correlated with those of the protein antigens. Among 12 peptides tested, P6-61, P6-123, and protein D-167 epitopes were better recognized than others in human serum. These findings might contribute to the development of an effective serotypeindependent vaccine for H. influenzae. Haemophilus influenzae is one of the normal inhabitants of the human nasopharynx and is responsible for pneumonia, acute otitis media (AOM), and acute rhinosinusitis (1-3). The presence or absence of a polysaccharide capsule segregates this bacterial species into two well-defined groups: one group of encapsulated strains and another group of noncapsulated strains, commonly referred to as nontypeable H. influenzae (NTHi) (3). Common infections caused by NTHi include otitis media in children and lower airway infections of chronic obstructive pulmonary disease in adults (4, 5). Vaccines composed of polysaccharide capsule conjugated to protein carriers have virtually eliminated infections caused by encapsulated H. influenzae type b, including meningitis and other systemic infections, in regions where the vaccines are widely administered (6, 7). However, these conjugate vaccines have no effect on infections caused by NTHi, and in regions with H. influenzae type b vaccination programs, nontypeable strains are now the most common cause of noninvasive H. influenzae infection, so that the development of the vaccine against NTHi is an urgent and challenging task (8-10).Since NTHi organisms are noncapsulated bacteria, the outer membrane proteins (OMPs) are the main targets for vaccine designers. Several research groups have identified conserved surface proteins and tested them as putative vaccines, and the conserved NTHi antigens with demonstrated preclinical protective capacity have been identified, among which P6 and protein D are the most widely studied (11)(12)(13)(14).Experimental data derived from humans and animal models indicate t...

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“…l EUCAST clinical breakpoint for categorization of susceptibility to amoxicillin-clavulanic acid (14). in several geographical regions (6,(8)(9)(10)(11), and reliable detection and susceptibility categorization of this organism have become increasingly important. Commonly used acceptance criteria are Ͼ90% essential agreement for MIC determination and Ͻ1.5% VME and Ͻ3% ME for susceptibility categorization (16).…”

Section: Discussionmentioning

confidence: 99%

“…The distinction is clinically important because high-rPBP3 strains express higher resistance to extended-spectrum cephalosporins (1,2,(4)(5)(6). Group II low-rPBP3 is the predominating genotype in Australia (7), Europe (8,9), and North America (6,10), whereas high-rPBP3 strains predominate in Japan and Korea (6,11).…”

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Haemophilus influenzae with Non-Beta-Lactamase-Mediated Beta-Lactam Resistance: Easy To Find but Hard To Categorize

et al. 2015

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Haemophilus influenzae is a major pathogen, and beta-lactams are first-line drugs. Resistance due to altered penicillin-binding protein 3 (rPBP3) is frequent, and susceptibility testing of such strains is challenging. A collection of 154 beta-lactamase-negative isolates with a large proportion of rPBP3 (67.5%) was used to evaluate and compare Etest (Haemophilus test medium [HTM]) and disk diffusion (EUCAST method) for categorization of susceptibility to aminopenicillins and cefuroxime, using MICs generated with broth (HTM) microdilution and clinical breakpoints from CLSI and EUCAST as the gold standards. In addition, the proficiency of nine disks in screening for the rPBP3 genotype (N526K positive) was evaluated. By Etest, both essential and categorical agreement were generally poor (<70%), with high very major errors (VME) (CLSI, 13.0%; EUCAST, 34.3%) and falsely susceptible rates (FSR) (CLSI, 87.0%; EUCAST, 88.3%) for ampicillin. Ampicillin (2 g) with adjusted (؉2 mm) zone breakpoints was superior to Etest for categorization of susceptibility to ampicillin (agreement, 74.0%; VME, 11.0%; FSR, 28.3%). Conversely, Etest was superior to 30 g cefuroxime for categorization of susceptibility to cefuroxime (agreement, 57.1% versus 60.4%; VME, 2.6% versus 9.7%; FSR, 7.1% versus 26.8%). Benzylpenicillin (1 unit) (EUCAST screening disk) and cefuroxime (5 g) identified rPBP3 isolates with highest accuracies (95.5% and 92.2%, respectively). In conclusion, disk screening reliably detects rPBP3 H. influenzae, but false ampicillin susceptibility is frequent with routine methods. We suggest adding a comment recommending high-dose aminopenicillin therapy or the use of other agents for severe infections with screening-positive isolates that are susceptible to aminopenicillins by gradient or disk diffusion. N ontypeable Haemophilus influenzae (NTHi) frequently causes acute otitis media, conjunctivitis, sinusitis, and respiratory tract infections, including pneumonia and exacerbations in chronic obstructive pulmonary disease and cystic fibrosis, and may also cause invasive disease (1). Beta-lactams are first-line drugs when systemic therapy is indicated, but resistance due to transferable beta-lactamase genes (bla TEM or bla ROB ) and/or substitutions in penicillin-binding protein 3 (PBP3), encoded by the ftsI gene, is common (1, 2). Strains with low-level PBP3-mediated resistance (low-rPBP3) possess the R517H (group I) or the N526K (group II) substitution, whereas strains with high-level resistance (high-rPBP3) are characterized by the additional substitution S385T (2, 3). The distinction is clinically important because high-rPBP3 strains express higher resistance to extended-spectrum cephalosporins (1, 2, 4-6). Group II low-rPBP3 is the predominating genotype in Australia (7), Europe (8, 9), and North America (6, 10), whereas high-rPBP3 strains predominate in Japan and Korea (6, 11).Susceptibility testing of H. influenzae has been characterized as "a tricky business" (12). Categorization of susceptibility to aminopenicillins (wi...

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Invasive Haemophilus influenzae in British Columbia: non-Hib and non-typeable strains causing disease in children and adults

Cited by 47 publications

References 29 publications

Classification, Identification, and Clinical Significance of Haemophilus and Aggregatibacter Species with Host Specificity for Humans

Classification, Identification, and Clinical Significance of Haemophilus and Aggregatibacter Species with Host Specificity for Humans

Serum Concentrations of Antibodies against Outer Membrane Protein P6, Protein D, and T- and B-Cell Combined Antigenic Epitopes of Nontypeable Haemophilus influenzae in Children and Adults of Different Ages

Haemophilus influenzae with Non-Beta-Lactamase-Mediated Beta-Lactam Resistance: Easy To Find but Hard To Categorize

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