eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease
Haemophilus Influenzae Infection: Treatment & Medication
Updated: Nov 20, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Medical care depends on the disease syndrome. Children with invasive Haemophilus influenzae disease require careful attention and, often, intensive care. Medical care depends on the organ system or problems involved, as follows:
- CNS: Lumbar puncture should be considered in a child with invasive H influenzae type b (Hib) disease. Complications, including subdural effusion, ventriculitis, infarction, abscess, sensorineural deafness, and developmental delay, must be considered.
- Neonatal disease: Routine therapy with ampicillin and gentamicin for presumptive neonatal sepsis may not be effective if an ampicillin-resistant strain of Hib is the cause of the infection.
- Meningitis: Prompt use of intravenous antibiotics and good supportive care are the mainstays of therapy.
- Fluid and electrolyte disturbances: Seizures may be due to hyponatremia as a result of syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The fluid status must be closely monitored in children with Hib meningitis, and the use of fluids, particularly hypo-osmolar fluids, on an ad-lib basis is contraindicated.
Surgical Care
Consultation with a surgeon may be required in some children with invasive Hib disease. Procedures that may be necessary include the following:
- Tracheotomy - For Hib epiglottitis when the airway cannot be managed with endotracheal intubation
- Arthrocentesis or bone debridement - For osteomyelitis or septic arthritis, particularly involving the hip
- Neurosurgery - For subdural empyema complicating meningitis or intracranial complications of orbital cellulitis3
- Surgical drainage - For septic arthritis of the hip joint
- Open drainage - For most cases of septic arthritis of the shoulder
- Early pericardectomy - For pericarditis; the treatment of choice, used in conjunction with antibiotics
Consultations
Depending on the manifestations of invasive H influenzae disease, consultants required may include neurologists, neurosurgeons, orthopedic surgeons, anesthesiologists, critical care physicians, and infectious diseases physicians. An audiologist should evaluate all children after they receive treatment for H influenzae meningitis.
Medication
Antibiotic agents
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Aggressive parenteral antibiotic therapy is required for severe forms of Haemophilus influenzae disease, particularly those caused by the type b strain. More mild forms of disease (ie, sinopulmonary infections caused by nontypeable strains of Haemophilus organisms) may be treated with various oral antibiotics. Only therapies for invasive H influenzae infection are reviewed here.
Third-generation cephalosporins have become the cornerstone of therapy for invasive H influenzae infections, including meningitis, because of their potent bacteriocidal activity and penetration into the subarachnoid space.
Semisynthetic penicillins, particularly ampicillin, may be useful in H influenzae meningitis if the isolate is beta-lactamase negative.
Ceftriaxone (Rocephin)
Third-generation cephalosporin with broad-spectrum gram-negative activity, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. Arrests bacterial growth by binding to 1 or more penicillin-binding proteins.
Adult
Uncomplicated infections: 250 mg IM once; not to exceed 4 g
Severe infections: 1-2 g IV qd or divided bid; not to exceed 4 g/d
Pediatric
Neonates >7 days: 25-50 mg/kg/d IV/IM; not to exceed 125 mg/d
Infants and children: 50-75 mg/kg/d IV/IM divided q12h; not to exceed 2 g/d
Important note: Relative contraindication in neonates because of concern of hyperbilirubinemia; do not use in infants unless a normal bilirubin level has been documented
Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Documented hypersensitivity; neonates (relative contraindication due to hyperbilirubinemia)
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in renal impairment; caution in breastfeeding women and in patients with an allergy to penicillin; relative contraindication in neonates because of concern of hyperbilirubinemia; do not use in infants unless a normal bilirubin level has been documented
Cefotaxime (Claforan)
Arrests bacterial cell wall synthesis, which in turn inhibits bacterial growth. Third-generation cephalosporin with gram-negative spectrum. Lower efficacy against gram-positive organisms.
Adult
Moderate-to-severe infections: 1-2 g IV/IM q6-8h
Life-threatening infections: 1-2 g IV/IM q4h; not to exceed 12 g/d
Pediatric
<12 years: 50-180 mg/kg/d IV/IM divided q4-6h; higher doses, up to 200 mg/kg/d, should be used when S pneumoniae infection is possible
>12 years: Administer as in adults
Probenecid may increase levels; coadministration with furosemide and aminoglycosides may increase nephrotoxicity
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in severe renal impairment; has been associated with severe colitis
Cefepime (Maxipime)
So-called fourth-generation cephalosporin with good gram-negative coverage. Similar to third-generation cephalosporins but has better gram-positive coverage. Excellent penetration into CNS; indicated for treatment of adult and pediatric meningitis.
Adult
1-2 g IV q12h for 5-10 d
Pediatric
>2 months: 50 mg/kg IV q8h; not to exceed 2 g/dose
Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, or aminoglycosides may increase nephrotoxicity
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in severe renal insufficiency; prolonged use may predispose patients to superinfection
Meropenem (Merrem)
Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell-wall synthesis. Effective against most gram-positive and gram-negative bacteria. Has slightly increased activity against gram-negative species and slightly decreased activity against staphylococci and streptococci compared with imipenem. In contrast to imipenem, indicated for treatment of bacterial meningitis, including pediatric meningitis.
Adult
Mild-to-moderate infections: 1 g IV q8h
Meningitis: 2 g IV q8h
Pediatric
40 mg/kg IV q8h; not to exceed 6 g/d
Probenecid may inhibit renal excretion of meropenem, increasing levels
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Pseudomembranous colitis and thrombocytopenia (immediately discontinue medication)
Chloramphenicol (Chloromycetin)
Binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.
Adult
50-100 mg/kg/d IV divided q6h for 10 d; not to exceed 4 g/d; oral formulations not currently available in United States
Pediatric
50-75 mg/kg/d IV divided q6h
With concurrent barbiturates, levels may decrease while barbiturate levels increase, causing toxicity (may be relevant in child with meningitis and active seizures who requires anticonvulsant therapy); manifestations of hypoglycemia may occur with sulfonylureas; rifampin may reduce levels, presumably through hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity; levels may be increased or decreased as needed
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use only for indicated infections or as prophylaxis for bacterial infections; serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur; determine baseline and periodic blood levels approximately q2d during therapy; discontinue if reticulocytopenia, leukopenia, thrombocytopenia, anemia, or findings attributable to chloramphenicol occur; adjust dose in liver or kidney dysfunction; caution in pregnancy at term or during labor (potential toxic effects on fetus; gray syndrome)
Ampicillin (Marcillin, Omnipen, Polycillin, Principen)
Agent with cell wall activity that interferes with transpeptidation step of peptidoglycan biosynthesis. Has bactericidal activity against susceptible organisms. Resistance of H influenzae to ampicillin occurs in 10-40% of patients. Use in combination with chloramphenicol.
Adult
0.5-3 g IV q4-6h; not to exceed 12 g/d
Pediatric
100-400 mg/kg/d IV/IM divided q4-6h
H influenzae meningitis: 400 mg/kg/d IV divided q4-6h; not to exceed 12 g/d
Probenecid and disulfiram elevate levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction; never should be used as an empiric single-agent therapy for presumptive meningitis because of high incidence of resistance among H influenzae isolates (ie, beta-lactamase–positive strains); addition of clavulanate (ie, ampicillin and sulbactam) is not recommended for meningitis therapy (sulbactam does not cross blood-brain barrier adequately)
Glucocorticoids
Glucocorticosteroids elicit anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli. Use of adjunctive glucocorticosteroid therapy has been demonstrated to decrease the risk of sensorineural deafness in children with H influenzae meningitis.
Dexamethasone (Decadron)
For various allergic and inflammatory diseases. Decreases inflammation by suppressing migration of PMNs and reducing capillary permeability. For maximum benefit, corticosteroids should be initiated as soon as possible in treatment of H influenzae meningitis, ideally prior to the first dose of antibiotics.
Adult
Pediatric
0.15 mg/kg IV q6h for 4 d has been shown to decrease the incidence of sensorineural deafness
Effects decrease with coadministration of barbiturates, phenytoin, and rifampin; may decrease effects of salicylates and vaccines
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Increases risk of multiple complications, including severe infections; monitor adrenal insufficiency when tapering; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications of glucocorticoid use; may mask persistent fevers during treatment of bacterial meningitis
Vaccines
Active immunization increases resistance to infection. Vaccines consist of microorganisms or cellular components, which act as antigens. Administration of the vaccine stimulates production of antibodies with specific protective properties. For a complete overview of current vaccine recommendations, see the Advisory Committee on Immunization Practices (ACIP) guidelines from the Centers for Disease Control and Prevention (CDC).4
Haemophilus B vaccines (ActHIB)
Used for routine immunization of children against invasive diseases caused by H influenzae type b by decreasing nasopharyngeal colonization. CDC's ACIP recommends that all children receive one of the conjugate vaccines licensed for infant use beginning routinely at age 2 mo.
Adult
Not indicated
Pediatric
Regimens vary depending on product; one example follows:
ActHIB:
2-6 months: 0.5 mL IM q2mo for 3 doses (ie, ideally administered at age 2 mo, 4 mo, and 6 mo)
7-11 months, previously unvaccinated: 0.5 mL IM q2mo for 2 doses
12-14 months, previously unvaccinated: 0.5 mL IM once
Booster dose: All receive 0.5 mL at age 15-18 mo or at least 2 mo after last dose of immunization series; if aged 15-71 mo and previously unvaccinated, 0.5 mL IM is given only once
Corticosteroids or cyclosporine may inhibit full immunologic response
Documented hypersensitivity (including sensitivity to thimerosal)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Delay immunization if febrile illness evident; may cause erythema, swelling, or tenderness; cause-effect relationship with observed postvaccine Guillain-Barré syndrome has not been established
Chemoprophylaxis
Chemoprophylaxis is used to prevent secondary disease. With widespread success of immunization, chemoprophylaxis now is of mostly historical interest.
Rifampin (Rimactane, Rifadin)
Inhibits RNA synthesis in bacteria by binding to beta subunit of DNA-dependent RNA polymerase, which in turn blocks RNA transcription.
Adult
600 mg PO qd for 4 d
Pediatric
<12 years: 20 mg/kg PO qd for 4 d
>12 years: Administer as in adults
Induces microsomal enzymes, which may decrease effects of acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, oral contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFT results occur)
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Obtain CBC counts and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur
More on Haemophilus Influenzae Infection |
| Overview: Haemophilus Influenzae Infection |
| Differential Diagnoses & Workup: Haemophilus Influenzae Infection |
 Treatment & Medication: Haemophilus Influenzae Infection |
| Follow-up: Haemophilus Influenzae Infection |
| References |
| « Previous Page | Next Page » |
References
Burns IT, Zimmerman RK. Haemophilus influenzae type B disease, vaccines, and care of exposed individuals. J Fam Pract. Sep 2000;49(9 Suppl):S7-13; quiz S14. [Medline].
Friesen CA, Cho CT. Characteristic features of neonatal sepsis due to Haemophilus influenzae. Rev Infect Dis. 1977;8:777. [Medline].
Lessner A, Stern GA. Preseptal and orbital cellulitis. Infect Dis Clin North Am. Dec 1992;6(4):933-52. [Medline].
Kroger AT, Atkinson WL, Marcuse EK, Pickering LK. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. Dec 1 2006;55:1-48. [Medline]. [Full Text].
Ward J, Lieberman JM, Cochi S. Haemophilus influenzae vaccines. In: Plotkin S, Mortimer E, eds. Vaccines. 1994:337.
Dajani AS, Asmar BI, Thirumoorthi MC. Systemic Haemophilus influenzae disease: an overview. J Pediatr. Mar 1979;94(3):355-64. [Medline].
Hamlin J, Senthilnathan S, Bernstein HH. Update on universal childhood immunizations. Curr Opin Pediatr. Aug 2008;20(4):483-9. [Medline].
Lebel MH, Freij BJ, Syrogiannopoulos GA, et al. Dexamethasone therapy for bacterial meningitis. Results of two double- blind, placebo-controlled trials. N Engl J Med. Oct 13 1988;319(15):964-71. [Medline].
Murphy TF, Apicella MA. Nontypable Haemophilus influenzae: a review of clinical aspects, surface antigens, and the human immune response to infection. Rev Infect Dis. Jan-Feb 1987;9(1):1-15. [Medline].
Rubin LG, Moxon ER. Pathogenesis of bloodstream invasion with Haemophilus influenzae type b. Infect Immun. Jul 1983;41(1):280-4. [Medline].
Shapiro ED, Ward JI. The epidemiology and prevention of disease caused by Haemophilus influenzae type b. Epidemiol Rev. 1991;13:113-42. [Medline].
St Geme JW. The pathogenesis of nontypable Haemophilus influenzae otitis media. Vaccine. 2000;8; Suppl 1:S41-50. [Medline].
Further Reading
Keywords
Haemophilus influenzae type b, Haemophilus influenzae B, the flu, H.flu, Hib, HIB, HiB, HITB, influenza, H influenzae, influenza infection, bacterial meningitis, Hib disease, Hib meningitis, invasive Hib disease, Hib epiglottitis, otitis media, conjunctivitis, bronchitis, sinusitis, septicemia, meningitis, cellulitis, septic arthritis, epiglottitis, pneumonia, respiratory tract infection, bacteremia, eustachian tube dysfunction, sickle cell disease, asplenia, agammaglobulinemia, Hodgkin disease, complement deficiencies, Brazilian purpuric fever, BPF, osteomyelitis, meningococcemia, cerebritis, ventriculitis, intracerebral abscess, hydrocephalus, respiratory distress, endophthalmitis, glossitis, uvulitis, thyroiditis, endocarditis, lung abscess, epididymitis, peritonitis, intraperitoneal abscesses, hepatobiliary disease, brain abscesses
