eMedicine Specialties > Infectious Diseases > Bacterial Infections

Haemophilus Influenzae Infections: Treatment & Medication

Author: Vidya R Devarajan, MD,
Contributor Information and Disclosures

Updated: Aug 12, 2008

Treatment

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.⁷
• 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 loss⁸ and other neurological complications.9
• 10
• 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.⁸
• 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.11 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.12
• 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.13
• 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.⁷
• 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.

Medication

Initially, patients with invasive and serious H influenzae infections are best treated with an intravenous third-generation cephalosporin.

Antibiotics

Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting. Penicillins are useful in management of mucosal infections caused by nonencapsulated H influenzae. As many as 25-50% of isolates produce beta-lactamase; therefore, they are resistant to this class of drugs. Third-generation cephalosporins are highly effective in H influenzae infections. Meropenem or ampicillin and chloramphenicol are alternative regimens.

Azithromycin (Zithromax)

Acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected.
Concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.
Treats mild-to-moderate microbial infections.

Plasma concentrations are very low, but tissue concentrations are much higher, giving it value in treating intracellular organisms. Has a long tissue half-life.

Cefotaxime (Claforan)

Third-generation cephalosporin with gram-negative spectrum. Lower efficacy against gram-positive organisms.

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms; arrests bacterial growth by binding to one or more penicillin-binding proteins. Exerts antimicrobial effect by interfering with synthesis of peptidoglycan, a major structural component of bacterial cell wall. Bacteria eventually lyse because of the ongoing activity of cell wall autolytic enzymes while cell wall assembly is arrested. Highly stable in presence of beta-lactamases, both penicillinase and cephalosporinase, of gram-negative and gram-positive bacteria. Approximately 33-67% of dose excreted unchanged in urine, and remainder secreted in bile and, ultimately, in feces as microbiologically inactive compounds. Reversibly binds to human plasma proteins, and binding has been reported to decrease from 95% bound at plasma concentrations <25 mcg/mL to 85% bound at 300 mcg/mL.

Cefuroxime (Ceftin, Zinacef)

This second-generation cephalosporin maintains gram-positive activity of first-generation cephalosporins; adds activity against Proteus mirabilis, H influenzae, Escherichia coli, Klebsiella pneumoniae, and Moraxella catarrhalis. Binds to penicillin-binding proteins and inhibits final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death. It is not recommended for treatment of Hib meningitis but may be used for other Hib infections. Condition of patient, severity of infection, and susceptibility of microorganism determine proper dose and route of administration.

Ampicillin (Marcillin, Omnipen, Polycillin, Principen)

Broad-spectrum penicillin. Interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take PO medication.

Amoxicillin (Trimox, Amoxil, Trimox)

Derivative of ampicillin and has similar antibacterial spectrum, namely certain gram-positive and gram-negative organisms. Superior bioavailability and stability to gastric acid and has broader spectrum of activity than penicillin. Somewhat less active than that of penicillin against pneumococcus. Penicillin-resistant strains also resistant to amoxicillin, but higher doses may be effective. More effective against gram-negative organisms (eg, Neisseria meningitidis, H influenzae) than penicillin. Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Amoxicillin and clavulanic acid (Augmentin)

Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. Addition of clavulanate inhibits beta-lactamase–producing bacteria. Good alternative antibiotic for patients allergic or intolerant to the macrolide class. Is usually well tolerated and provides good coverage to most infectious agents. Not effective against Mycoplasma and Legionella species. The half-life of oral dosage form is 1-1.3 h. Has good tissue penetration but does not enter CSF. For children >3 months, base dosing protocol on amoxicillin content. Because of different amoxicillin/clavulanic acid ratios in 250-mg tab (250/125) vs 250-mg chewable tab (250/62.5), do not use 250-mg tab until child weighs >40 kg. The bid dosing schedule reduces incidence of diarrhea.

Chloramphenicol (Chloromycetin)

May be used in patients who are allergic to penicillins and cephalosporins. Binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Active in vitro against a wide variety of bacteria, including gram-positive, gram-negative, aerobic, and anaerobic organisms. Well-absorbed from GI tract and metabolized in the liver, where it is inactivated by conjugation with glucuronic acid and then excreted by the kidneys. Oral form is not available in the United States.

Erythromycin and sulfisoxazole (Eryzole, Pediazole)

Erythromycin is a macrolide antibiotic with a large spectrum of activity. Erythromycin binds to the 50S ribosomal subunit of the bacteria, which inhibits protein synthesis. Sulfisoxazole expands erythromycin's coverage to include gram-negative bacteria. Sulfisoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid. Good choice for PO therapy for otitis media. May be used in patients who are allergic to penicillins and cephalosporins.

Meropenem (Merrem IV)

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.

Rifampin (Rifadin)

Used for chemoprophylaxis in Hib infections.

Glucocorticoids

These agents are used as adjunctive therapy in H influenza meningitis for the anti-inflammatory effects and prevention of sensorineural deafness. Administer before or with antibiotics, not after. Utility of steroids has been demonstrated primarily in nonimmunized children, and its usefulness in adults or vaccinated children is not known.

Dexamethasone (Decadron, Baldex)

Has many pharmacologic benefits but significant adverse effects. Stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentration, and inhibits prostaglandin and proinflammatory cytokines (eg, TNF-alpha, IL-6, IL-2, and IFN-gamma). The inhibition of chemotactic factors and factors that increase capillary permeability inhibits recruitment of inflammatory cells into affected areas. Suppresses lymphocyte proliferation through direct cytolysis and inhibits mitosis. Breaks down granulocyte aggregates and improves pulmonary microcirculation.
Adverse effects are hyperglycemia, hypertension, weight loss, GI bleeding or perforation synthesis, cerebral palsy, adrenal suppression, and death. Most of the adverse effects of corticosteroids are dose-dependent or duration-dependent.
Readily absorbed via the GI tract and metabolized in the liver. Inactive metabolites are excreted via the kidneys. Lacks salt-retaining property of hydrocortisone.
Patients can be switched from an IV to PO regimen in a 1:1 ratio.

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