American Journal of Hematology 48:278-279 (1 995)

Multi-Drug Resistance to Streptococcus pneumoniae in Sickle Cell Anemia

Wing-Yen Wong, Darleen R. Powars, and Alan L. Hiti Department of Pediatrics, Division of Hematology/Oncology (W.-Y.W., D.R.P.), and Department of Pathology (A.L.H.), University of

Southern California School of Medicine, Los Angeles

Key words: pneumococcal infection, sickle cell anemia, Streptococcus pneumoniae

INTRODUCTION

An ominous increase in the incidence of penicillin and cephalosporin resistant Streptococcus pneumoniae infec- tion worldwide has been recently noted [1-4]. Risk fac- tors for the development of resistant strains include previ- ous antibiotic use, repeat hospitalizations, and day care center attendance. Young children with sickle cell ane- mia (SCA) certainly are at increased risk because they receive daily antibiotics and are frequently hospitalized. Wang et al. reported the emergence of intermediate level penicillin resistant pneumococcal infection in 2 children with SCA in the Memphis, Tennessee, area [5]. This is the first report of multi-drug resistant pneumococcal in- fection within the SCA population.

CASE REPORT

A 23-month-old girl with SCA was brought to the hospital with a temperature of 104"F, lethargy, and sple- nomegaly. She had no meningismus or respiratory diffi- culty. The child had been receiving daily penicillin pro- phylaxis since age 3 months and had received a dose the morning and evening of admission. The family had been compliant with all clinic visits with regular refills for penicillin prescriptions.

The child had not received pneumococcal vaccine, but was scheduled to receive it in 1 month. Diagnosis of SCA was made at birth on HPLC by the State of California Program for Newborn Hemaglobinopathy Screening.

Intravenous Cefutaxime at 100 mg/kg/day following a loading dose of 25 mg/kg and vancomycin at 60 mg/kg/ day was initiated. Initial hemoglobin concentration of 7.9 g/dl decreased to 6 g/dl within 12 hr requiring filtered packed red cell transfusion. Initial white count was 46,200 cells/mm3, with a differential count of 65% seg- mented neutrophils, 12% bands, 10% monocytes, 12% lymphocytes, and circulating normoblasts present. Plate- let count was 422,000/mm3. Within 2 days, the patient was afebrile and the white count had markedly decreased. 0 1995 Wiley-Liss, Inc.

Blood aerobic cultures grew serogroup 15 S. pneumoniae (Danish nomenclature, Microbiology Reference Labora- tory) which was characterized as a multi-drug resistant isolate in standard MIC testing (Table I) using recom- mended media (Difco, Detroit, MI) [6]. Published labo- ratory standards define the MIC antibiotic resistance cri- teria [3,4,6]. After 7 days of intravenous therapy, she was discharged home on prophylactic oral Cefixime at 8 mg/kg/day .

COMMENT

The threat of multi-drug resistant pneumococcal infec- tions to children with SCA is a present danger. We have to adopt a heightened vigilance against multi-drug resis- tant organisms in the SCA child with suspected bacterial sepsis and/or meningitis despite penicillin or cephalo- sporin-based antibiotic prophylaxis. Community surveil- lance of the sensitivity patterns of prevalent pneumococ- cal organisms from children under age 4 years is essen- tial. A recent report documents that 17.8% of S. pneumoniae surveillance isolates in the United States are penicillin resistant to some degree [7]. Within the LAC+USC Medical Center, 10 of 84 (11.9%) pneumo- coccal isolates from normally sterile body fluids during the last 17 months were resistant to penicillin (9/84 inter- mediate resistance; 1/84 high resistance; 2 of the 3 with MICs 2 1 kg/ml were from children).

This child had not received pneumococcal vaccine al- though she was on penicillin prophylaxis. Serogroup 15 has not often been reported in relation to vaccine failure, but has been reported to have developed multi-drug resis- tance [4]. We attribute the child's uneventful recovery

Received for publication October 4, 1994; accepted October 12, 1994.

Address reprint requests to Wing-Yen Wong, M.D. , LAC+USC Med- ical Center, Department of Pediatrics, 1240 N. Mission St., Rm L916, Los Angeles, CA 90033.

Brief Report: Multi-Drug Resistant Pneumococcal Infections 279

TABLE 1. Susceptibility of S. pneumoniae isolate to Various Antibiotics

Level of susceptibility Antibiotic

High resistance Chloramphenicol Clindamycin Erythromycin Tetracycline

Pencillina TrimethopridSulfa

Cefazolinb Ciprofloxacinb Rifampinb Vancomycin

Intermediate resistance

Sensitive

MIC (Wml)

16 >2 >4 >8

1 2/38

2 1

<1 <1

”Pencillin sensitive: MIC < 0.06 pglml; penicillin intermediate resistance: MIC = 0.1-1 pg/ml; penicillin high resistance: MIC 2 2.0 pg/ml. bResistance criteria according to National Committee for Clinical Labora- tory Standards, Vol. 11, No. 17, M100-S3, M7-A2, Table 2; Villanova, PA. Dec. 1991.

from this resistant pneumococcus to the understanding of the infection risk by the mother and her rapid seeking of medical attention.

Although the efficacy of polysaccharide pneumococcal vaccine for serotypes 6, 14, 19, and 23 is reduced in SCA children under age 4 years, vaccine efficacy improves and is marked by persistent high antibody titers in the older child [8,9]. Administration of the 23 serotype pneu- mococcal vaccine at 2 years of age followed by a booster at 3-5 years provides most SCA children with protective antibody levels to the 23 serotypes in the vaccine [9]. Conjugate polysaccharide protein S . pneumoniae vac- cines are currently in early clinical trials.

Data prior to the use of pneumococcal vaccine and prophylactic antibiotics showed a spontaneous decrease in the incidence of S . pneumoniae infection after 4 years of age which plateaued by age 10 [ 101. Discontinuance of prophylactic antibiotics at the time that anti-pneumococ- cal antibodies reach protective levels appears to be rea-

sonably safe. Enlightened parental involvement, compli- ance with prophylaxis, and timely vaccinations are essential. However, it is not only prudent but crucial for healthcare providers to be knowledgable of the emer- gence of multi-drug resistant S . pneumoniae strains and the antibiotic susceptibilities in their communities to pro- vide optimum care for the febrile SCA child. The use of intravenous vancomycin with or without rifampin in the young SCA child should be strongly considered in the face of the rapid emergence of multidrug-resistant pneu- mococcal strains in the SCA pediatric population.

REFERENCES

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