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Epidemiologic Notes and Reports Erythromycin-Resistant Bordetella pertussis -- Yuma County, Arizona, May-October 1994
In 1993, a total of 6586 cases of pertussis was reported in the United States, including 70 in Arizona. On June 27, 1994, a case of Bordetella pertussis disease caused by a strain resistant to erythromycin was reported to the Arizona Department of Health Services (ADHS) from Yuma County (1990 population: 106,895). Susceptibility testing at CDC confirmed that the isolate was highly resistant to erythromycin with a minimum inhibitory concentration (MIC) greater than 64 ug/mL. The MIC of erythromycin against B. pertussis usually ranges from 0.02 ug/mL to 0.1 ug/mL, and resistant isolates have not been previously reported (1). This report summarizes the case investigation and describes efforts to enhance surveillance for pertussis in Arizona. Case Report
The erythromycin-resistant strain was isolated from a 2-month-old male infant living in Yuma County, Arizona, who had onset of cough on May 16, 1994. The illness was initially diagnosed as bronchitis, and treatment with amoxicillin was initiated on May 23. The infant had no history of previous antibiotic therapy, and the parents reported he had not received pertussis vaccine before the onset of illness. On May 26, he was hospitalized with severe paroxysmal cough, inspiratory whoop, posttussive vomiting, and episodes of cyanosis and apnea. B. pertussis infection was diagnosed by direct fluorescent antibody (DFA) testing; oral erythromycin estolate therapy (50 mg per kg body weight per day) was initiated on May 26 and continued for 12 days. Because of persistent paroxysmal cough and episodes of cyanosis, apnea, and bradycardia, on June 8 he was transferred to a pediatric intensive-care facility.
Both a DFA test and culture performed on nasopharyngeal secretions obtained on June 8 confirmed the persistence of pertussis organisms, and intravenous erythromycin therapy (30 mg/kg/day) was initiated. On June 13, a repeat DFA test and culture were positive, and the erythromycin dosage was increased to 40 mg/kg/day. Despite sequential oral and parenteral erythromycin therapy, nasopharyngeal cultures obtained from the infant on June 16 and 20 grew B. pertussis, and his condition remained unchanged. Susceptibility testing at the hospital laboratory suggested that the isolate was resistant to erythromycin but sensitive to trimethoprim-sulfamethoxazole (TMP-SMZ). On June 20, erythromycin therapy was discontinued, and therapy with TMP-SMZ was initiated; the infant's condition improved rapidly. A nasopharyngeal culture obtained on June 25 was negative, and he was discharged from the hospital on June 29.
Approximately 2 weeks before the infant's onset of illness, his 17-year-old mother had developed a spasmodic cough illness associated with posttussive vomiting. A nasopharyngeal culture specimen obtained from the mother on June 28 was negative. She had no history of recently receiving antibiotic treatment. Enhanced Surveillance for Pertussis
Because of the case in the 2-month-old infant, in late June, the Yuma County Department of Public Health enhanced surveillance to detect pertussis illness and to obtain B. pertussis isolates from county residents. State and federal public health officials visited all primary-care providers and health-care facilities in Yuma County to disseminate culture kits and instructions for obtaining appropriate culture specimens. In particular, providers were asked to obtain nasopharyngeal cultures from all Yuma County residents with an unexplained acute cough illness lasting 7 or more days. In addition, ADHS mailed letters to approximately 2500 primary-care providers in Arizona to encourage collection of nasopharyngeal cultures for diagnosis of pertussis. Health officials in two California counties near Yuma County (Imperial and San Diego counties) were alerted to the isolation of an erythromycin-resistant pertussis strain in Yuma County.
The first person with a culture-confirmed case of B. pertussis in Yuma County in 1994 had onset on April 9. A total of 18 confirmed cases (eight culture-confirmed and 10 epidemiologically linked to a culture-confirmed case) and 57 probable cases (defined as unexplained acute cough for 14 or more days) were identified during April 30-October 1. During the period of enhanced surveillance (late June-October 1), a total of 127 nasopharyngeal culture specimens were obtained from Yuma County residents and sent to the ADHS laboratory. In addition to the index case, B. pertussis was isolated from the specimens of seven persons. Of these seven isolates, one was inadvertently discarded, and the remaining six were susceptible to erythromycin. In addition, all 22 B. pertussis strains isolated during June-August from persons in other Arizona counties and all 13 B. pertussis strains isolated during January- August from patients in San Diego County were susceptible to erythromycin.
ADHS has continued enhanced surveillance and has recommended that providers in Arizona obtain nasopharyngeal culture specimens from all persons -- regardless of age or vaccination status -- with unexplained acute cough of 14 or more days' duration and at least one of the following symptoms: paroxysms of cough, inspiratory whoop, or posttussive vomiting. Health-care providers also have been urged to report all suspected cases to local health departments and to send B. pertussis culture specimens to the ADHS laboratory.
Preliminary results of studies at CDC suggest that the mechanism of B. pertussis resistance to erythromycin does not involve ribosomal riboneucleic acid methylation, which has been documented in streptococcal and staphylococcal resistance to erythromycin. Studies are ongoing at CDC to elucidate the mechanism of B. pertussis resistance to erythromycin. Reported by: S Lewis, MPH, Public Health Nursing Staff, Yuma County Dept of Public Health, Yuma; B Erickson, PhD, G Cage, MS, G Harter, State Public Health Laboratory; C Kioski, MPH, S Barefoot, L Carmody, MA, H Houser, L Sands, DO, State Epidemiologist, Arizona Dept of Health Svcs; M Saubolle, PhD, Good Samaritan Regional Medical Center, K Lewis, MD, S Barbour, MD, M Rudinsky, MD, Children's Hospital, Phoenix. Hospital Infections Program, and Div of Bacterial and Mycotic Diseases, National Center for Infectious Diseases; National Immunization Program, CDC.
Editorial Note: Erythromycin is the drug of choice for treating persons with B. pertussis disease and for postexposure prophylaxis of all household members and other close contacts as recommended by the Advisory Committee on Immunization Practices (2-6). For adults who are susceptible to pertussis because of a decrease in vaccine-induced immunity or for infants who are too young to be adequately vaccinated and are at risk for severe disease, erythromycin prophylaxis and treatment are the primary control measures.
Because of the limited number of isolates subjected to susceptibility testing (n=41), the proportion of resistant strains of B. pertussis cannot be estimated accurately for Yuma County or other areas in the region. However, the absence of additional erythromycin-resistant strains in Arizona and San Diego County, California, suggests that antimicrobial resistance is not widespread. Ongoing surveillance and collection of B. pertussis isolates should assist in more accurate assessment of the extent of transmission of the resistant strain in the area.
Failure of erythromycin to eradicate B. pertussis has been associated with poor absorption of some preparations of the antibiotic (4,7). Among the three esterified oral erythromycin formulations (estolate, ethylsuccinate, and stearate), erythro- mycin estolate has superior bioavailability and achieves higher concentrations in serum and respiratory secretions. TMP-SMZ is an alternative for treatment and for chemoprophylaxis, but its efficacy as a chemoprophylactic agent has not been evaluated (8).
Nasopharyngeal cultures should be obtained from persons with pertussis who do not improve with erythromycin therapy. Criteria for assessing treatment failure are 1) persistence or worsening of the typical symptoms * of pertussis disease, 2) initiation of erythromycin therapy within 2 weeks of onset of illness, 3) completion of erythromycin therapy in the recommended dosage, and 4) verification of patient compliance with therapy. Most persons who meet these criteria will not be culture-positive for B. pertussis; however, isolates obtained from patients with erythromycin therapy failure should be sent to CDC (Pertussis Laboratory, Childhood Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, CDC, Mailstop C-02, 1600 Clifton Road, NE, Atlanta, GA 30333) for further testing. Tests to evaluate antimicrobial susceptibility of B. pertussis have not been standardized and are not widely available. In collaboration with ADHS, efforts to standardize B. pertussis susceptibility testing are ongoing at CDC.
All health-care providers in the United States are encouraged to obtain nasopharyngeal cultures from patients in whom pertussis is suspected. These include persons with unexplained acute cough of 14 or more days' duration and at least one of the following symptoms: paroxysms of cough, inspiratory whoop, or posttussive vomiting, regardless of the patient's age or vaccination status. All probable and confirmed cases of pertussis should be reported promptly to local or state health departments.
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