Multiply resistant Haemophilus influenzae type b causing meningitis: Comparative clinical and laboratory study

doi:10.1016/S0022-3476(86)80923-4

The Journal of Pediatrics

Volume 108, Issue 6, June 1986, Pages 897-902

https://doi.org/10.1016/S0022-3476(86)80923-4 Get rights and content

Thirty-five patients with meningitis caused by Haemophilus influenzae type b were admitted to our hospital from January 1981 to December 1984; 60% of the strains were resistant to ampicillin, 65.7% to chloramphenicol, and 57% to both antibiotics. No significant differences in age, sex, previous treatment, clinical symptoms, outcome, and mortality were found between the 20 patients whose strains were resistant to both ampicillin and chloramphenicol and the other 15 patients whose strains were susceptible to ampicillin, chloramphenicol, or both. Alternative therapeutic agents were a combination of carbenicillin and gentamicin and new cephalosporins. At present, cefotaxime is our treatment of choice for meningitis caused by H. Influenzae type b.

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Cited by (53)

Clinical significance of cerebrospinal fluid inhibitory titers of antibiotics, based on pharmacokinetic/pharmacodynamic parameters, in the treatment of bacterial meningitis
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The cerebrospinal fluid (CSF) inhibitory titer (CSF-IT) of an antibiotic, which can be used to estimate the duration of time above the agent’s MIC in the CSF, was introduced as one of the indices to evaluate the effectiveness of antibiotic selection in treating bacterial meningitis. The CSF-IT was determined via a microdilution method. A suspension of the causative organism was added to a tube containing twofold diluted CSF and double-concentrated Mueller-Hinton broth with supplement. The CSF-IT was determined by the maximum point without turbidity of medium after overnight incubation at 37°C. Concerning the strain of β-lactamase-negative ampicillin-resistant Haemophilus influenzae (BLNAR), the killing rates of both meropenem and piperacillin were compared in an in vitro pharmacokinetic (PK) model, in which human pharmacokinetics in CSF were simulated. Organisms recovered from the CSF in 37 treated clinical cases of bacterial meningitis were H. influenzae, Streptococcus agalactiae, Streptococcus pneumoniae, Escherichia coli, and Neisseria meningitidis; in these cases, the CSF-IT ranged from 1: 8 to as high as 1: 4 096. In the in vitro PK model, the concentrations of both drugs were higher than the MICs over a period of 24 h; however, the killing rate of piperacillin was higher than that of meropenem, and bacterial regrowth was observed after the administration of meropenem. A CSF-IT value higher than 1: 32 indicates that the antibiotic concentration in the CSF exceeds the MIC for 24 h. The effect of piperacillin on BLNAR depends not only on the time above MIC of 24 h but also on the maximum concentration in the CSF.
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2009, Feigin and Cherry's Textbook of Pediatric Infectious Diseases, Sixth Edition
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Citation Excerpt :
Antimicrobial susceptibility patterns, specifically the emergence of beta-lactamase –producing strains, have greatly influenced the antimicrobial agents used to treat meningitis caused by H. influenzae type B; these strains accounted for approximately 24% of all isolates in 27 states of the United States from 1978 through 1981 and 32% of all isolates in a study of 5 states and Los Angeles county in 1986.83 Resistance of H. influenzae to chloramphenicol has also been described, although more often from areas such as Spain than from the United States.8,29 Even in patients whose isolates are chloramphenicol-sensitive, a recent prospective study found chloramphenicol to be bacteriologically and clinically inferior to ampicillin, ceftriaxone, or cefotaxime in the therapy of childhood bacterial meningitis caused predominantly by H. influenzae type B.54
Animal models have been invaluable in our understanding of the use of antibacterial agents in the therapy of central nervous system (CNS) infections.⁷⁷ Although in vitro susceptibility testing may give information regarding the activity of an antibacterial agent against a bacterial pathogen, the in vivo effectiveness of a drug may be very different. The animal model of meningitis most frequently used for therapeutic studies at the present time is the rabbit model, which uses an intracisternal method for organism inoculation.¹⁶ The intracisternal route of inoculation appears to be the most reliable method for producing experimental meningitis in animals, although there are several disadvantages: (1) the natural route of dissemination to the cerebrospinal fluid (CSF) is bypassed so the pathogenesis is artificial; (2) early bacteremia and death may supervene prior to CSF inflammation; (3) extravasation into the surrounding tissues may occur; (4) direct trauma to the medulla oblongata may result in cardiorespiratory arrest; and (5) anesthetics and analgesics used during experiments may alter the pathophysiology of meningitis by inducing hypotension, hypoventilation, or both. In addition, other predisposing conditions (e.g., history of head trauma, splenectomy, immunosuppression) that may be present in patients with meningitis are not taken into consideration in experimental models; these factors may have significant roles in the pathogenesis of bacterial meningitis.³⁹ Despite these disadvantages, the intracisternal route of inoculation in the rabbit model is preferred because of easy handling of the animals, relative inexpense, and sufficient CSF volume allows frequent sampling of CSF for quantitative antimicrobial and bacterial concentrations during the treatment period. This model also permits quantitation of the relative penetration of drug into CSF, the effects of meningitis on this entry parameter, and the relative bactericidal efficacy within purulent CSF.
It is beyond the scope of this article to review the use of antibacterial agents in the therapy of all CNS infections. Therefore, we focus on meningitis (for which there is the most experimental and clinical data) and review the basic therapeutic principles for use of antibacterials in this infection and give recommendations for specific antibacterial agents for therapy in patients with bacterial meningitis.
Immunization for Haemophilus influenzae type b: Effects on mortality and morbidity in children under five years of age
1998, Seminars in Pediatric Infectious Diseases
Haemophilus influenzae is a small gram-negative pleomorphic coccobacillus. The H influenzae type b (Hib) strain is especially important because, prior to the advent of effective Hib vaccines, the organism was the cause of 95% to 98% of severe invasive infection, including meningitis, epiglottitis, cellutitis, sepsis, pneumonia, and osteomyelitis, in children less than 5 years of age. An important microbiologic feature of H influenzae is its development of resistance to a wide variety of antibiotics, including sulfonamides, trimethoprim-sulfamethoxazole, erythromycin, tetracycline, and penicillin. Ampicillin resistance is now widespread, ranging between 5% and 40% of all isolates in various parts of the world. The current mainstays of treatment are third-generation cephalosporins, but the potential for increased resistance to them, as well as other factors, has underscored the need for prophylactic measures. Since the early 1970s, when the capsular polysaccharide of Hib was purified, characterized, and shown to be immunogenic, tremendous strides have been made worldwide to immunize children against the organism and to irradicate the bacteria. A steady decline in the incidence of Hib diseases has occurred since the introduction in 1990 of Hib conjugate vaccines for infants. Because of this rapid decline, Hib diseases among children less than 5 years of age is targeted for elimination in the United States. This article provides an overview of the discovery and characterization of the organism and a review of the literature on the impact that the Hib vaccines have had on morbidity and mortality rates among children less than 5 years of age.
Empirical treatment of acute purulent meningitis
1997, International Journal of Infectious Diseases

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Original articleMultiply resistant Haemophilus influenzae type b causing meningitis: Comparative clinical and laboratory study

J Pediatr

Lancet

Lancet

Am J Med

Bacterial meningitis and meningococcemia United States—1978

MMWR

Ampicillin-resistant Haemophilus influenzae—Texas

MMWR

Ampicillin-resistant Haemophilus influenzae meningitis—Maryland, Georgia

MMWR

Increasing ampicillin-resistance rates in Haemophilus influenzae meningitis

Am J Dis Child

A 12 year review of the antibiotic management of Haemophilus influenzae meningitis. Comparison of ampicillin and conventional therapy including chloramphenicol

J Pediatr

Ampicillin and chloramphenicol resistance in systemic Haemophilus influenzae disease

MMWR

Meningitis due to Haemophilus influenzae type b resistant to both ampicillin and chloramphenicol

Pediatrics

Meningitis due to beta lactamase producing type b Haemophilus influenzae resistant to chloramphenicol

Br Med J

Plasmid-mediated resistance in multiply resistant Haemophilus influenzae type b causing meningitis: molecular characterization in one strain and review of the literature

J Infect Dis

Cefuroxime treatment of bacterial meningitis in infants and children

Antimicrob Agents Chemother

Invasive infections caused by multiply resistant Haemophilus influenzae type b

J Pediatr

Original article
Multiply resistant Haemophilus influenzae type b causing meningitis: Comparative clinical and laboratory study