Elsevier

Archives of Medical Research

Volume 31, Issue 6, November–December 2000, Pages 592-598
Archives of Medical Research

Original article
Clinical Outcome of Invasive Infections in Children Caused by Highly Penicillin-Resistant Streptococcus pneumoniae Compared with Infections Caused by Penicillin-Susceptible Strains

https://doi.org/10.1016/S0188-4409(00)00244-7Get rights and content

Abstract

Background

In this report based on data from the Institutional Surveillance System during 1994–1998, we document the continuing emergence of drug-resistant Streptococcus pneumoniae strains at the Hospital Infantil de Mexico Federico Gómez in Mexico City.

Methods

We evaluate the clinical course of 49 invasive pneumococcal infection outside the central nervous system (CNS) by a number of factors including the site, severity, and place where the infection was acquired, the underlying health of the patient, and the adequacy of antimicrobial therapy.

Results

An underlying illness was present in 21 of 49 (43%) patients, 37 (75%) patients had taken previous antimicrobial therapy, and 25% of the infections were nosocomially acquired. Overall, 25 of 49 (51%) of the pneumococcal strains tested were pencillin-resistant; strains with the highest resistance to penicillin were also resistant to cephalosporins. Twenty-two percent of all strains were considered to be multidrug-resistant. Eleven of 25 penicillin-resistant strains were identified as multidrug-resistant, i.e., to erythromycin, TMP/SMX, and chloramphenicol. Ten serotypes accounted for 88% of the isolates, the most frequent serotypes being 23F, 14, 19V, 6A, and 6B. The overall case-fatality rate was 37% (18 of 49), with most deaths occurring within 3–5 days after antibiotic therapy was initiated. There was no difference in the case fatality rate between children with penicillicin-nonsusceptible and penicillin-susceptible pneumococcal infections; instead; case-fatality rate correlated with severity of illness on admission and presence of underlying disease.

Conclusions

Characterizing groups at risk for invasive pneumococcal disease could aid in the development of preventive programs and increase the benefits from wide use of future conjugated vaccines.

Introduction

Streptococcus pneumoniae (S. pneumoniae) is a leading cause of infectious disease-associated morbidity and mortality worldwide. Local and systemic infections caused by S. pneumoniae include otitis media and sinusitis as less serious but very common illnesses, as well as bacteremia, pneumonia, sepsis, and meningitis 1, 2, all serious bacterial infections. Many diseases are potentially vaccine-preventable 3, 4, 5.

Drug-resistant strains of S. pneumoniae were relatively uncommon in Mexico through 1993 6, 7, 8, 9, 10, 11, and penicillin was selected as the drug-of-choice for the empiric treatment of severe pneumococcal infections for more than 50 years. The presence of strains with diminished susceptibility to penicillin and other agents is now recognized worldwide, and as this problem continues to increase in incidence, selection for the empirical treatment of these infections may need to be changed.

It is accepted that penicillin therapy is inappropriate for the treatment of penicillin-resistant pneumococcal meningitis 12, 13, 14, 15. However, there is little evidence to suggest that penicillin-resistant S. pneumoniae infections outside the CNS respond poorly to therapy with penicillin or an equivalent beta lactam 16, 17, 18, 19, 20, 21. Serum concentrations of penicillin or other beta lactams much greater than minimal inhibitory concentrations (MICs) for most penicillin-resistant strains are achieved with standard dosages, relevant in nonmeningeal infections.

In this report, we correlate the clinical course of invasive pneumococcal infections with a number of factors that includes site and severity of infection, underlying health of the patient, adequacy of antimicrobial therapy, and comparison of the clinical outcome of infections other than meningitis that are caused by highly penicillin-resistant or penicillin-susceptible S. pneumoniae.

Section snippets

Methods

From March 1995 to June 1999, we undertook a 4-year prospective study at the Hospital Infantil de Mexico Federico Gómez, a teaching and referral hospital serving a population of more than 1,000,000 inhabitants in Mexico City. This was a nonintervention study in which children with invasive pneumococcal infection were followed prospectively until resolution of clinical signs and symptoms. Patients were included in the protocol as soon as culture results of blood, pleural fluid, and other

Isolates

During the study period, all S. pneumoniae isolated from normally sterile body fluids of children with invasive disease were collected prospectively and stored frozen (−70°C). Strains of S. pneumoniae were identified by standard methods (22), i.e., susceptibility to optochin and bile solubility.

Serotyping

The swelling test with omniserum pools and type/group-specific antisera from Statens Seruminstitut, Copenhagen, Denmark was used.

Antimicrobial susceptibility

All strains were routinely screened for susceptibility to penicillin with

Results

Of all cases of culture-proven invasive S. pneumoniae disease, 28 (57%) were male and 21 (43%), female. Patients' ages ranged from 1 month to 11 years (median age, 16 months); 35 (71%) were ≤2 years of age.

The sources of the specimens from which S. pneumoniae were isolated and comparison of clinical features in 49 children with severe invasive pneumococcal infections who were divided in two groups according to penicillin susceptibility are presented in Table 1.

Thirty-seven (37 of 49, 75%)

Discussion

The prevalence of antimicrobial resistance of Streptococcus pneumoniae strains responsible for invasive infections in children at Hospital Infantil de Mexico Federico Gómez is very high, and has increased over the last 3 years, similar to other reports 17, 21, 25, 26, 27.

At our hospital, approximately 30% of patients admitted to having an underlying disease, mainly dealing with hemato-oncologic processes, immunosuppression, and malnutrition. Some of these patients acquired the pneumococcal

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