Hib vaccine guidance
Patients aged < 12 mos
Follow routine Hib vaccination recommendations
Patients aged 12–59 mos
If unimmunized or received 0 or 1 dose before age 12 mos: 2 doses, 8 wks apart
Patients aged < 60 months undergoing chemotherapy or radiation therapy†
If routine Hib doses administered ≥14 days before starting therapy: revaccination not required
Patients aged ≥15 mos undergoing elective splenectomy
If unimmunized:§ 1 dose prior to procedure¶
Asplenic patients aged >59 mos and adults
If unimmunized:§ 1 dose
HIV-infected children aged ≥60 mos
If unimmunized:§ 1 dose
Hib vaccination is not recommended
Recipients of hematopoietic stem cell transplant, all ages
Regardless of Hib vaccination history: 3 doses (at least 4 wks apart) beginning 6–12 mos after transplant
*Persons with functional or anatomic asplenia, HIV infection, immunoglobulin deficiency including immunoglobulin G2 subclass deficiency, or early component complement deficiency, recipients of a hematopoietic stem cell transplant, and those receiving chemotherapy or radiation therapy for malignant neoplasms.
More effective microbiologically than amoxicillin, with ~100% susceptibility, as the addition of beta-lactamase inhibitor means that this drug treats all isolates.
Drug for serious infections.
A reliable, first-line choice that will treat beta-lactamase producers.
The drug not commonly used to treat H. influenzae, although resistance rates in U.S. < 2-3%.
Excellent activity with among the lowest MICs of the widely used FQ class.
Most isolates are susceptible, though resistance rates rising, and maybe more common in those on TMP/SMX prophylaxis.
The only member of the ketolide drug class related to macrolides, available in oral formulation; now only FDA-approved for pneumonia (CAP) due to concerns for potential hepatotoxicity. H. influenzae coverage is similar to azithromycin. Rarely used.
Member of fluoroquinolone class usually with excellent activity against Haemophilus species; however, not used empirically for lower respiratory tract infection due to poor activity against the pneumococcus.
Comment: Although no new recommendations issued, this guideline compiles all prior as well as background information and impact of the Hib conjugate vaccine. Children with HIV should receive Hib immunization.
Comment: This surveillance study found that the incidence of invasive nontypeable Haemophilus influenzae infections found a recent increase among people with HIV in Atlanta in the years 2017–2018 compared to the previous 8 years of 2008–2060. Investigators found to have unique but genetically related clonal strains that seem to cause septic arthritis among black men who had sex with men and lived in relatively close geographic proximity.
Comment: If this study from Ethiopia children with HIV were found to be frequently colonized with respiratory pathogens. Haemophilus influenzae were noted and 6% of children but this was significantly lower than the rates of staph aureus at 29%, Moraxella catarrhalis at 12.3% and Streptococcus pneumoniae at 10.3%. The lower rate of Haemophilus influenzae was comparable to some studies from Africa; however, was clearly lower than the 7.2% to 24.4% right-sided and other studies. It is unclear why this study had a lower colonization rate but may be due to the fact that participants under the age of 5 were not included in the study.
Comment: This analysis from the PERCH study helps provide evidence behind the biologically plausible but never well confirmed thought that higher rates of bacterial colonization and density correlate with increased risks of pneumonia.
Comment: Small study suggesting that Hib use in HIV-infected children dropped baseline colonization almost 10x. No outcomes in this study.
Comment: Haemophilus spp considered a pathogen in 6.8% of those presenting to an STD clinic in Spain.
Comment: A study of 211 HIV-infected (and 73 uninfected) immunized with Hib/MenCTT found similar responses in both populations. UK Guidelines suggest a single dose of Hib compared to no such recommendation in the US. No good data on outcome back the UK recs but the incidence of pneumonia is higher in HIV-infected.
Comment: Authors identify factors contributing to the emergence of H. influenzae serotype a (Hia) infection primarily driven by the success of the Hib since the 1990s. Laboratory surveillance has primarily identified the US and Canada as where most clinical infections have been described. For reasons that are unclear, the incidence of invasive Hia infection is lower in Europe. Much as had been the case for Hib, invasive Hia strikes children mostly ages 6 months to 2 years. In Manitoba, Hia caused ~30% of invasive H. influenzae infection.
Comment: The short duration of treatment (5d) appears to be as effective as 10d in this study from Malawi that includes HIV (+) children. H. influenzae was the second most common cause of infection.
Comment: The report notes the significant ongoing burden of >700,000 suspected cases of meningitis. Among these, 69,208 suspected cases were evaluated by laboratory data: 4,674 (7%) samples were culture-positive for bacterial infections under surveillance. 2,192 (47%) were positive for S. pneumoniae, 1,575 (34%) for Haemophilus influenzae, and 907 (19%) for N. meningitidis. The majority of the remaining culture results were negative.
Comment: Pediatric series (children < 15 yrs) found H. influenza type b the leading cause (14/43 cases, 33%) followed by pneumococci (21%). Authors emphasize that acute bacterial meningitis is a not uncommon cause of illness and hospitalization in sub-Saharan Africa and that the leading pathogens are vaccine-preventable.
Comment: Pneumococcus and Haemophilus influenzae remain the top two causes of bacterial meningitis in children. The Haemophilus fatality rate was 45%.
Comment: Routine Hib immunization has been performed in Kenya since 2001. This WHO report found it to be highly cost-effective. Rates of invasive H. influenzae infection declined by more than 80%.
Comment: South African experience describes a reduction in both Hib and non-typeable H. influenzae disease in HIV+ populations.
Comment: Though not routinely used in Africa, the introduction of Hib immunization appeared to reduce the incidence of infection in children < 5 by 12%, despite considerable HIV infection in this population.
Comment: Though not routinely recommended, Hib immunization did appear safe without significant alterations in VL or CD4. Antibody responses were judged suboptimal.
Comment: A published national survey of respiratory isolates showed that the overall rate of beta-lactamase production among 2706 isolates of H. influenzae examined in this study was 28.3%. 24 isolates (0.9%) found to be ampicillin-resistant despite failing to produce beta-lactamase. Among beta-lactams tested cefotaxime was most active (MIC90 0.12 mg/L) irrespective of beta-lactamase production. In contrast, cefprozil had relatively poor activity against beta-lactamase-positive isolates with an MIC90 of >8 mg/L. Telithromycin (MIC90 4 mg/L) more potent than clarithromycin, and as potent as azithromycin vs. H. influenzae, irrespective of beta-lactamase status. Gatifloxacin and moxifloxacin were the most potent FQ with MIC90 values of 0.03 mg/L.
Comment: Small study examining vaccine responses in HIV infected children before and after HAART. Authors conclude that repeat immunizations can improve titers in those with previously undetectable responses when performed after institution of HAART.
Comment: One of the few HIV-specific reports regarding H. influenzae comes from Spain. In this study, most pts were severely immunosuppressed; 73% had a CD4 < 100. Subacute clinical presentation observed in 27% and was associated with a higher degree of immunosuppression. Authors conclude that this pathogen mainly afflicts those with advanced HIV, and note surprising attributable mortality of ~11%.
Comment: South African report suggesting that HIV+children have a relative risk (RR) ratio of 22.1 compared to HIV-negative children for H. influenzae type b.
Comment: A large study of 1200 HIV+ pts with community-acquired pneumonia and PCP. Multivariate logistic regression showed that patients less likely than controls to have used TMP-SMX prophylaxis (OR, 0.22; 95% CI, 0.12-0.41) and more likely to have been hospitalized previously with pneumonia (OR, 6.25; CI, 3.40-11.5). The authors suggest that these findings reconfirm the efficacy of TMP-SMX in preventing community-acquired pneumonia.
Comment: Rate of bacteremic Haemophilus pneumonia >100-fold greater in HIV+ patients than the general population. The author suggests that H. influenzae infection in HIV+ pts does not require anything other than customary treatment for community-acquired pneumonia.
Comment: Spanish study emphasizing that Haemophilus bacteremia is no longer a disease in children. 116 pts had bacteremia (0.26 cases per 1000 admissions) with HIV the most common underlying condition [29%]. The HIV+ pts mainly presented with bilateral pneumonia. In this cohort that included HIV-negative adults, ABx resistance was reported: 11% to chloramphenicol, 48% to ampicillin, 78% to erythromycin, 76% to TMP-SMX, 15% to rifampin, and 57% to clarithromycin.
Comment: Series from the pre-HAART era in patients with advanced HIV suggesting that these pts are at risk of recurrent bacterial bronchitis. The most common pathogens in 18 episodes of bacterial bronchitis were H. influenzae and Streptococcus pneumoniae (5 episodes each) and Pseudomonas aeruginosa (4 episodes). Moreover, they believe repeated bacterial bronchitis may lead to bronchiectasis, which may be more common in HIV infection than generally appreciated.
Comment: U.S. study finding ~25% of H. influenzae bacteremia occurred in adults. 194 cases of invasive H. influenzae occurred (annual incidence 5.6 cases/100,000 population), of which 47 (24%) were in adults ≥18 (annual incidence of 1.7 cases/100,000 adults). Adults with invasive H. influenzae ranged from 18 to 96 yrs; 79% were women. Bacteremic pneumonia accounted for 70% of adult cases. Other sources for invasive H. influenzae in adults were obstetric infections, epiglottitis, and tracheobronchitis; 1 pt had meningitis. Underlying conditions noted in 92% of pts with chronic bronchitis; HIV was most common but, cancer and pregnancy also reported. Interestingly, half of the bacteremic cases were due to H. influenzae type b, which causes a much smaller minority of non-bacteremic Haemophilus infections.
Trantracheal aspirate showing some Gram negative rods, but also Gram negative diplococci that were found in culture to be H. influenzae.
Source: CDC, Dr. Michael Miller
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