Haemophilus Influenzae Infections Treatment & Management
- Author: Vidya R Devarajan, MD; Chief Editor: Burke A Cunha, MD more...
Medical Care
- Antibiotics and supportive care
- These are the mainstays of treatment.
- Initially, invasive and serious H influenzae type b (Hib) infections are best treated with an intravenous third-generation cephalosporin until antibiotic sensitivities become available. In Malawi, Africa, intramuscular ceftriaxone was compared with intravenous ceftriaxone and was not found to increase the mortality rate. This may be important in developing countries where the intravenous route may not be possible.[10]
- The site of infection and the clinical response determine the length of antibiotic treatment.
- Meningitis
- Administer parenteral antibiotics (eg, ceftriaxone, ceftazidime, cefotaxime, ampicillin-sulbactam, fluoroquinolones, azithromycin) to patients with uncomplicated meningitis for 7-14 days. Cefotaxime and ceftriaxone are the initial drugs of choice for suspected Hib meningitis.
- Once the susceptibilities are known, adjust antibiotics accordingly.
- Do not use ampicillin empirically, since as many as 50% of the isolates are resistant, usually because of plasmid-mediated beta-lactamase production.
- Cefuroxime is also not recommended because delayed sterilization is more common.
- Chloramphenicol produces adequate bactericidal blood and CSF levels but is now used infrequently because it requires monitoring of drug levels and can result in dose-dependent (though reversible) bone marrow toxicity (particularly in neonates and patients with liver disease) or an idiosyncratic aplastic anemia.
- Dexamethasone is an important adjunctive treatment in patients with meningitis who are older than 2 months because it has been shown to decrease the inflammatory response and the rate of hearing loss[11] and other neurological complications.[12]
- The 2004 Infectious Disease Society of America (IDSA) guidelines recommend that dexamethasone 0.15 mg/kg/d q6h for 2-4 days be administered to children (but not adults) with H influenzae meningitis. When steroids are used, they must be administered either prior to or along with antibiotics, as dexamethasone administered after antimicrobials is unlikely to be beneficial.[13]
- In January 2007, a systematic review of randomized controlled trials involving adjuvant corticosteroids therapy in acute bacterial meningitis found a significant benefit in children from developed countries but no beneficial or harmful effects in children in developing countries. This meta-analysis also found that dexamethasone administered to adults with community-acquired meningitis (including that caused by H influenzae) decreased the risk of mortality and neurologic sequelae. Based on data from 18 randomized controlled trials, the authors concluded that all adults and children with acute bacterial meningitis in developed countries who have good access to medical care should receive adjuvant corticosteroids. The authors also found no significant increase in adverse effects due to corticosteroids. The recommended dose for dexamethasone in adults and children is 0.6 mg/kg/d for 4 days.[11]
- A randomized prospective study in 1994 found that, in treatment for bacterial meningitis, a 2-day course of dexamethasone provided effectiveness similar to that of a 4-day course.[14] However, most studies recommend a 4-day dexamethasone course.
- In November 2007, a prospective randomized double-blind placebo-controlled trial studied adjuvant glycerol and dexamethasone in children with bacterial meningitis. All patients were given ceftriaxone and randomized to receive intravenous dexamethasone, oral glycerol, both agents, or neither agent. In addition, a subgroup of patients with Hib meningitis was studied. Findings showed that glycerol, an inexpensive osmotic diuretic that can be administered orally, reduced the incidence of neurologic sequelae and death. Dexamethasone prevented profound hearing loss when the timing of dexamethasone and ceftriaxone administration was not taken into account. Few adverse effects were found with either adjuvant medication. Additional studies need to be performed to evaluate the impact of glycerol in bacterial meningitis.[15]
- In 2007, a Vietnamese study evaluated the benefit of dexamethasone in adults and adolescents with confirmed or suspected bacterial meningitis. Overall, initial findings showed that dexamethasone did not decrease the mortality rate at 1 month or the incidence of mortality or disability at 6 months. However, when the results were compared with culture-proven disease, dexamethasone was found to confer a significant benefit in terms of both mortality and disability in patients with confirmed bacterial meningitis. Among the patients studied, only 7 had H influenzae meningitis, and 6 of these were in the placebo group.[16]
- In a 2007 study in Malawi, Africa, dexamethasone was given to adults with bacterial meningitis but was not found to reduce mortality or morbidity. However, 90% of the study patients had HIV infection. Of the 465 patients studied in this group, only 3 had H influenzae meningitis.[10]
- Treatment of H influenzae meningitis also includes ongoing supportive care and management of complications such as shock, inappropriate secretion of antidiuretic hormone syndrome, seizures, subdural empyema, and secondary foci of infection.
- Small, clinically insignificant subdural effusions are common.
- In uncomplicated cases, a repeat lumbar puncture is unnecessary to ensure sterility of the CSF.
- Cellulitis
- In patients with Hib cellulitis, administer parenteral antibiotics until the patient shows defervescence and the cellulitis subsides. Then, administer appropriate oral antibiotics until the course of therapy, usually 7-10 days, is finished. Empiric therapy for preseptal cellulitis should cover not only Hib but also S pneumoniae, Staphylococcus aureus, and group A beta-hemolytic streptococci. Patients with orbital cellulitis require at least 14 days of parenteral therapy.
- Surgical drainage may be needed for the underlying sinusitis or for orbital abscesses.
- Epiglottitis
- Maintenance of a patent airway via intubation or tracheostomy is the mainstay of treatment for epiglottitis.
- Administer antimicrobial therapy parenterally once the airway is secured, and continue until the patient can receive oral fluids. The total duration of therapy is 7-10 days.
- Arthritis
- So far, no studies have accurately defined the appropriate length of therapy for septic arthritis. However, uncomplicated septic arthritis usually requires systemic antibiotics for at least 7 days.
- If an appropriate clinical response is obtained, oral therapy for 2-3 weeks may follow. Therapy may continue beyond 3 weeks until the ESR begins to normalize. The ESR may lag behind successful clinical response for weeks; accordingly, the C-reactive protein test may be a more useful laboratory tool because its values tend to normalize more rapidly.
- Bacteremia and other Hib infections
- Bacteremia precedes essentially all invasive Hib infection.
- Approximately 30-50% of children with occult Hib bacteremia (bacteremia without an identifiable cause) develop a focus of infection such as meningitis, cellulitis, or pneumonia. Therefore, reevaluate these children (including with lumbar punctures and chest radiography) for an infectious focus and obtain repeat blood cultures.
- Administer parenteral antibiotics for at least 2-5 days and guide subsequent therapy based on the focus of infection. If no focus is identified, substitute oral antibiotics to complete 10 days of therapy. Patients with pericarditis, empyema, endocarditis, endophthalmitis, or osteomyelitis require an extended antibiotic treatment duration of 3-6 weeks.
- Nonencapsulated H influenzae
- These organisms can cause mucosal infections treatable with oral antibiotics. The first-line antibiotic for otitis media is amoxicillin (80-90 mg/kg/d for 7-10 d) because of its safety and low cost. If the organism produces beta-lactamase or if other treatment fails, treatment with amoxicillin-clavulanate is recommended. Penicillin-allergic individuals may be treated with erythromycin-sulfisoxazole or cefaclor. Cefaclor has weak activity against beta-lactamase–producing bacteria and causes a serum sickness–like illness in 2% of patients. Approximately 25-50% of NTHi strains produce beta-lactamase and, therefore, are resistant to amoxicillin and ampicillin.
- Oral antibiotics with activity against beta-lactamase–producing H influenzae include trimethoprim-sulfamethoxazole, cefuroxime axetil, cefixime, clarithromycin, azithromycin, and fluoroquinolones. The duration of therapy is 10 days for otitis media and at least 14 days for sinusitis. Patients with conjunctivitis should receive topical antibiotics such as sulfacetamide and erythromycin.
- Administer parenteral antibiotics to patients with invasive NTHi infection, which can be treated similarly to invasive Hib disease.
Surgical Care
- Patients with subdural and pleural empyema may require surgical drainage if orbital cellulitis is extensive.
- Patients with pericarditis require systemic antibiotics and drainage via early pericardectomy or pericardiostomy rather than multiple pericardiocentesis.
- Patients with septic arthritis of the hip require surgical drainage to avoid avascular necrosis of the femoral head. Repeated aspirations or surgical drain placement may be needed in other infected joints to reduce pressure.
Consultations
- Consult an ear, nose, and throat specialist and an anesthesiologist for help in securing difficult airways in all cases of suspected epiglottitis.
- Consult a neurosurgeon for suppurative complications of nervous system involvement.
- Consult an ophthalmologist for management of orbital cellulitis.
- Consult an infectious disease specialist for assistance with complicated infections.
- Consult an orthopedic surgeon for surgical drainage of a joint.
Jacups SP. The continuing role of Haemophilus influenzae type b carriage surveillance as a mechanism for early detection of invasive disease activity. Hum Vaccin. Dec 1 2011;7(12):[Medline].
Active Bacterial Core Surveillance Report, Emerging Infections Program Network Haemophilus Influenzae, 2006. Available at www.cdc.gov/ncidod/dbmd/abcs/survreports.hib.pdf.
Jin Z, Romero-Steiner S, Carlone GM, et al. Haemophilus influenzae type a infection and its prevention. Infect Immun. Jun 2007;75(6):2650-4. [Medline].
MacNeil JR, Cohn AC, Farley M, Mair R, Baumbach J, Bennett N, et al. Current epidemiology and trends in invasive Haemophilus influenzae disease--United States, 1989-2008. Clin Infect Dis. Dec 2011;53(12):1230-6. [Medline].
von Gottberg A, Cohen C, Whitelaw A, Chhagan M, Flannery B, Cohen AL, et al. Invasive disease due to Haemophilus influenzae serotype b ten years after routine vaccination, South Africa, 2003-2009. Vaccine. Nov 26 2011;[Medline].
Haemophilus Influenzae serotype b (Hib) disease. Available at www.cdc.gov/ncidod/dbmb/diseaseinfo/haeminfluserob_t.htm. Accessed Feb 15, 2008.
Roush SW, Murphy TV. Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States. JAMA. Nov 14 2007;298(18):2155-63. [Medline].
Singleton R, Hammitt L, Hennessy T, et al. The Alaska Haemophilus influenzae type b experience: lessons in controlling a vaccine-preventable disease. Pediatrics. Aug 2006;118(2):e421-9. [Medline].
Satola SW, Collins JT, Napier R, et al. Capsule gene analysis of invasive Haemophilus influenzae: accuracy of serotyping and prevalence of IS1016 among nontypeable isolates. J Clin Microbiol. Oct 2007;45(10):3230-8. [Medline].
[Best Evidence] Scarborough M, Gordon SB, Whitty CJ, et al. Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa. N Engl J Med. Dec 13 2007;357(24):2441-50. [Medline].
van de Beek D, de Gans J, McIntyre P, et al. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2007;(1):CD004405. [Medline].
McIntyre PB, Berkey CS, King SM, et al. Dexamethasone as adjunctive therapy in bacterial meningitis. A meta- analysis of randomized clinical trials since 1988. JAMA. Sep 17 1997;278(11):925-31. [Medline].
[Guideline] Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. Nov 1 2004;39(9):1267-84. [Medline].
Syrogiannopoulos GA, Lourida AN, Theodoridou MC, et al. Dexamethasone therapy for bacterial meningitis in children: 2- versus 4-day regimen. J Infect Dis. Apr 1994;169(4):853-8. [Medline].
Peltola H, Roine I, Fernandez J, et al. Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial. Clin Infect Dis. Nov 15 2007;45(10):1277-86. [Medline].
Nguyen TH, Tran TH, Thwaites G, et al. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. N Engl J Med. Dec 13 2007;357(24):2431-40. [Medline].
American Academy of Pediatrics. Red Book 2006: The Report of the Committee on Infectious Disease. In: American Academy of Pediatrics. Haemophilus infulenzae infections. 27th ed. 2006:310-318, 89.
American Academy of Pediatrics Committee on Infectious Diseases. Recommended childhood and adolescent immunization schedule: United States, 2005. Pediatrics. Jan 2005;115(1):182. [Medline].
Andrade AL, Martelli CM. Globalisation of Hib vaccination--how far are we?. Lancet. Jan 1-7 2005;365(9453):5-7. [Medline].
Barthel D, Singh B, Riesbeck K, Zipfel PF. Haemophilus influenzae Uses the Surface Protein E To Acquire Human Plasminogen and To Evade Innate Immunity. J Immunol. Jan 1 2012;188(1):379-85. [Medline].
Bozdogan B, Appelbaum PC. Macrolide resistance in Streptococci and Haemophilus influenzae. Clin Lab Med. Jun 2004;24(2):455-75. [Medline].
Centers for Disease Control and Prevention. Licensure of a Haemophilus influenzae type b (Hib) vaccine (Hiberix) and updated recommendations for use of Hib vaccine. MMWR Morb Mortal Wkly Rep. Sep 18 2009;58(36):1008-9. [Medline].
Centers for Disease Control and Prevention. Progress toward elimination of Haemophilus influenzae type b invasive disease among infants and children--United States, 1998-2000. MMWR Morb Mortal Wkly Rep. Mar 22 2002;51(11):234-7. [Medline].
Centers for Disease Control and Prevention. Updated recommendations for use of Haemophilus influenzae type b (Hib) vaccine: reinstatement of the booster dose at ages 12-15 months. MMWR Morb Mortal Wkly Rep. Jun 26 2009;58(24):673-4. [Medline].
Claesson BA, Trollfors B, Lagergard T, et al. Antibodies against Haemophilus influenzae type b capsular polysaccharide and tetanus toxoid before and after a booster dose of the carrier protein nine years after primary vaccination with a protein conjugate vaccine. Pediatr Infect Dis J. May 2005;24(5):463-4. [Medline].
Cunha BA. Cunha BA. Antibiotic Essentials. 7th ed. Royal Oak, Michigan: Physicians Press; 2008.
Daum R. Haemophilus influenzae. In: Behrman RE, Kliegman R, eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa: WB Saunders and Co; 2000:833-837.
Daza P, Banda R, Misoya K, et al. The impact of routine infant immunization with Haemophilus influenzae type b conjugate vaccine in Malawi, a country with high human immunodeficiency virus prevalence. Vaccine. Sep 11 2006;24(37-39):6232-9. [Medline].
de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med. Nov 14 2002;347(20):1549-56. [Medline].
Fickweiler K, Borte M, Fasshauer M, et al. Meningitis due to Haemophilus influenzae type f in an 8-year-old girl with congenital humoral immunodeficiency. Infection. Apr 2004;32(2):112-5. [Medline].
Gallaher TK, Wu S, Webster P, et al. Identification of biofilm proteins in non-typeable Haemophilus Influenzae. BMC Microbiol. 2006;6:65. [Medline].
Garner D, Weston V. Effectiveness of vaccination for Haemophilus influenzae type b. Lancet. Feb 1 2003;361(9355):395-6. [Medline].
Gessner BD, Sutanto A, Linehan M, et al. Incidences of vaccine-preventable Haemophilus influenzae type b pneumonia and meningitis in Indonesian children: hamlet-randomised vaccine-probe trial. Lancet. Jan 1-7 2005;365(9453):43-52. [Medline].
Gold R. Epidemiology of bacterial meningitis. Infect Dis Clin North Am. Sep 1999;13(3):515-25, v. [Medline].
Hall-Stoodley L, Hu FZ, Gieseke A, et al. Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media. JAMA. Jul 12 2006;296(2):202-11. [Medline].
Kelly DF, Moxon ER, Pollard AJ. Haemophilus influenzae type b conjugate vaccines. Immunology. Oct 2004;113(2):163-74. [Medline].
Leibovitz E, Jacobs MR, Dagan R. Haemophilus influenzae: a significant pathogen in acute otitis media. Pediatr Infect Dis J. Dec 2004;23(12):1142-52. [Medline].
McVernon J, Trotter CL, Slack MP, et al. Trends in Haemophilus influenzae type b infections in adults in England and Wales: surveillance study. BMJ. Sep 18 2004;329(7467):655-8. [Medline].
Mitchell V, Walker D, Zuber P, et al. Evidenced-based decision making about Hib vaccination. Lancet. Mar 12-18 2005;365(9463):936-7. [Medline].
Moxon ER, Murphy TF. Haemophilus influenzae. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 5th ed. New York, NY: Churchill Livingstone; 2000:2369-2378.
Murphy TF, Kasper DT. Infections due to Haemophilus influenzae, other Haemophilus species, the HACEK group, and other gram-negative bacilli. In: Braunwald E, Fauci AS, eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998:924-928.
Peltola H, Salo E, Saxén H. Incidence of Haemophilus influenzae type b meningitis during 18 years of vaccine use: observational study using routine hospital data. BMJ. Jan 1 2005;330(7481):18-9. [Medline].
Rudan I, Campbell H. The deadly toll of S pneumoniae and H influenzae type b. Lancet. Sep 12 2009;374(9693):854-6. [Medline].
Scheifele D, Halperin S, Law B, et al. Invasive Haemophilus influenzae type b infections in vaccinated and unvaccinated children in Canada, 2001-2003. CMAJ. Jan 4 2005;172(1):53-6. [Medline].
Starner TD, Zhang N, Kim G, et al. Haemophilus influenzae forms biofilms on airway epithelia: implications in cystic fibrosis. Am J Respir Crit Care Med. Jul 15 2006;174(2):213-20. [Medline].
Steinhoff M, Goldblatt D. Conjugate Hib vaccines. Lancet. Feb 1 2003;361(9355):360-1. [Medline].
Strausbaugh LJ. Haemophilus influenzae infections in adults: a pathogen in search of respect. Postgrad Med. Feb 1997;101(2):191-2, 195-6, 199-200. [Medline].
Ward JI, Kenneth MZ. Haemophilus influenzae. In: Feigin RD, Cherry JD, Fletcher J, eds. Textbook of Pediatric Infectious Diseases. 4th ed. Philadelphia, Pa: WB Saunders and Co; 1998:1464-1482.
Watt JP, Wolfson LJ, O'Brien KL, Henkle E, Deloria-Knoll M, McCall N, et al. Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates. Lancet. Sep 12 2009;374(9693):903-11. [Medline].

