Monica M. Farley

Colistin is an important last-line antibiotic to treat highly resistant Enterobacter infections. Resistance to colistin has emerged among clinical isolates but has been associated with a significant growth defect. Here, we describe a clinical Enterobacter isolate with a deletion of mgrB, a regulator of colistin resistance, leading to high-level resistance in the absence of a growth defect. The identification of a path to resistance unrestrained by growth defects suggests colistin resistance could become more common in Enterobacter.

Haemophilus influenzae is a small gram-negative rod that colonizes the human respiratory tract.¹ Lack of a polysaccharide capsule distinguishes nontypeable H influenzae (NTHi) from encapsulated serotypes (a-f).² Nontypeable H influenzae is genetically diverse and is classified into 8 biotypes; some of these biotypes harbor genetic elements suggesting capsular ancestry, which may contribute to pathogenesis.^3-5 Although NTHi is frequently associated with noninvasive respiratory infections (eg, sinusitis, bronchitis), severe invasive disease may occur.^6,7 In addition, colonization of the female genital tract can lead to obstetrical infections and neonatal sepsis.⁸

Influenza and pneumonia combined are the leading causes of death due to infectious diseases in the United States. We describe factors associated with pneumonia among adults hospitalized with influenza. Through the Emerging Infections Program, we identified adults ≥ 18 years, who were hospitalized with laboratory-confirmed influenza during October 2005 through April 2008, and had a chest radiograph (CXR) performed. Pneumonia was defined as the presence of a CXR infiltrate and either an ICD-9-CM code or discharge summary diagnosis of pneumonia. Among 4,765 adults hospitalized with influenza, 1392 (29 %) had pneumonia. In multivariable analysis, factors associated with pneumonia included: age ≥ 75 years, adjusted odds ratio (AOR) 1.27 (95 % confidence interval 1.10–1.46), white race AOR 1.24 (1.03–1.49), nursing home residence AOR 1.37 (1.14–1.66), chronic lung disease AOR 1.37 (1.18–1.59), immunosuppression AOR 1.45 (1.19–1.78), and asthma AOR 0.76 (0.62–0.92). Patients with pneumonia were significantly more likely to require intensive care unit (ICU) admission (27 % vs. 10 %), mechanical ventilation (18 % vs. 5 %), and to die (9 % vs. 2 %). Pneumonia was present in nearly one-third of adults hospitalized with influenza and was associated with ICU admission and death. Among patients hospitalized with influenza, older patients and those with certain underlying conditions are more likely to have pneumonia. Pneumonia is common among adults hospitalized with influenza and should be evaluated and treated promptly.

Background: Racial differences have been well described for invasive pneumococcal disease (IPD), but little information exists on how race interacts with community socioeconomic factors. Methods: The Active Bacterial Core surveillance/Emerging Infections Program performed active surveillance for IPD in the 20-county Metropolitan Atlanta area. All IPD cases among children younger than 5 years from 2001 to 2009 were geocoded and linked to census tract-level socioeconomic measures from the 2000 US Census. Race- and socioeconomic-specific average annual incidence rates per 100,000 population were calculated. Trends in IPD incidence were determined by χ² tests for trend. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated using Poisson regression. Results: IPD incidence among the total population of children increased as percentage of household poverty increased (P = 0.002), as median household income decreased (P < 0.001), as wealth decreased (P = 0.018) and as percentage of individuals with less than a high school education increased (P = 0.023). After stratifying by race, there was no significant linear trend between socioeconomic characteristics and IPD incidence among white children; among black children, however, IPD incidence decreased as socioeconomic conditions worsened. Despite adjusting for sex and socioeconomic factors, the IPD rate remained higher among black children compared with white children (RR = 1.60; 95% CI: 1.39–1.84). Differences in RR of IPD associated with highest poverty and lowest wealth noted in 2001 [RR = 2.71 (95% CI: 2.17–3.39) and 1.80 (95% CI: 1.09–2.96), respectively] declined in 2009 [RR = 1.33 (95% CI: 0.90–1.96) and 0.76 (95% CI: 0.48–1.19), respectively]. Conclusions: Although socioeconomic disparities in IPD incidence exist among children, the association between socioeconomic characteristics and IPD rates may differ by race and may change over time. Community-level socioeconomic factors did not account for racial differences in IPD incidence.

A subset of invasive nontypeable Haemophilus influenzae (NTHI) strains has evidence of IS 1016 , an insertion element associated with division I H. influenzae capsule serotypes. We examined IS 1016 -positive invasive NTHI isolates collected as part of Active Bacterial Core Surveillance within the Georgia Emerging Infections Program for the presence or absence of hmw1 and hmw2 (two related adhesin genes that are common in NTHI but absent in encapsulated H. influenzae ) and hia (homologue of hsf , an encapsulated H. influenzae adhesin gene). Isolates were serotyped using slide agglutination, confirmed as NTHI strains using PCR capsule typing, and biotyped. Two hundred twenty-nine invasive NTHI isolates collected between August 1998 and December 2006 were screened for IS 1016 ; 22/229 (9.6%) were positive. Nineteen of 201 previously identified IS 1016 -positive invasive NTHI isolates collected between January 1989 and July 1998 were also examined. Forty-one IS 1016 -positive and 56 randomly selected IS 1016 -negative invasive NTHI strains were examined. The hia adhesin was present in 39 of 41 (95%) IS 1016 -positive NTHI strains and 1 of 56 (1.8%) IS 1016 -negative NTHI strains tested; hmw ( hmw1 , hmw2 , or both) was present in 50 of 56 (89%) IS 1016 -negative NTHI isolates but in only 5 of 41 (12%; all hmw2 ) IS 1016 -positive NTHI isolates. IS 1016 -positive NTHI strains were more often biotype V ( P < 0.001) or biotype I ( P = 0.04) than IS 1016 -negative NTHI strains, which were most often biotype II. Pulsed-field gel electrophoresis revealed the expected genetic diversity of NTHI with some clustering based on IS 1016 , hmw or hia , and biotypes. A significant association of IS 1016 with biotypes V and I and the presence of hia adhesins was found among invasive NTHI. IS 1016 -positive NTHI strains may represent a unique subset of NTHI strains, with characteristics more closely resembling those of encapsulated H. influenzae .

A 19-kb DNA region containing genes involved in the biosynthesis of the capsule of Haemophilus influenzae serotype f (Hif) has been cloned and characterized. The Hif cap locus organization is typical of group II capsule biosynthetic loci found in other H. influenzae serotype b bacteria and other gram-negative bacteria. However, the Hif cap locus was not associated with an IS 1016 element. Three new open reading frames, Fcs1, Fcs2, and Fcs3, were identified in the Hif capsule-specific region II. The chromosomal location of the Hif cap locus and the organization of the flanking sequences differed significantly from previously described division I H. influenzae serotypes.

The complete capsule ( cap ) loci from three Haemophilus influenzae strains, one serotype b (Hib) and two nonencapsulated b capsule-negative variants, were sequenced. Two new open reading frames, hcsA and hcsB , were identified in region III and thought to be involved in postpolymerization modification of the capsule. The location of the cap locus in the Haemophilus influenzae chromosome was identified within section 97 of the Rd genome (chromosomal coordinates 1074542 to 1086327) and found to be the same for the Hib and two Hib ⁻ strains as well as some other encapsulated division I H. influenzae strains.