Secondary prophylaxis of Rhodococcus equi pneumonia in HIV infection: breakthrough despite rifampicin/erythromycin suppressive therapy


Interest in effective treatment of Rhodococcus equi infections is increasing as this opportunistic pathogen is more frequently isolated from immunocompromised patients. Antibiotic therapy of pulmonary or disseminated infections has remained difficult, and relapses after termination of chemotherapy are common. This has prompted a call for secondary prophylaxis in immunocompromised patients [1]. We report here a severe case of R. equi pneumonia in an AIDS patient that responded well to intravenous antibiotic therapy. However, relapse occurred even while the patient was on continuing oral rifampin/erythromycin prophylaxis.

A 33-year-old HIV-infected patient was admitted with a productive cough of 2 months’ duration, fever (39.5°C) and night sweats for 1 week, and 3 kg weight loss. The patient's stage of HIV disease was CDC B3, with a CD4 cell count of 20/μL. He was receiving prophylaxis against Pneumocystis carinii with 160 mg trimethoprim/800 mg sulfamethoxazole daily, and zidovudine 250 mg twice daily. Elevated temperature (38.5°C) was the only abnormality detected on examination, and the patient did not appear to be severely ill. A chest X-ray revealed an infiltrate in the right middle lobe with abscess formation and hilar lymphadenopathy. Sputum and bronchoalveolar lavage (BAL) cultures yielded growth of Gram-positive coccobacilli which were identified as R. equi by conventional biochemical tests. Diagnosis was confirmed by direct sequencing of the small ribosomal subunit RNA. Disk diffusion tests and minimum inhibitory concentration (MIC) determination by the broth microdilution method (National Committee for Clinical Laboratory Standards) showed that the primary isolate was susceptible to gentamicin, ofloxacin/ciprofloxacin, erythromycin, and vancomycin, but was only intermediately susceptible to amoxicillin/sulbactam (Table 1). On this basis, initial therapy with oral amoxicillin/sulbactam was changed to oral ciprofloxacin, 500 mg twice-daily. The patient's clinical response was excellent and, as the X-ray abnormalities had resolved, therapy was stopped after 4 weeks.

Table 1.  Susceptibility pattern of the Rhodococcus equi isolate
Antimicrobial agentDisk diffusionMIC microbroth (μg/mL) 
  1. r=resistant; i=intermediate; s=susceptible; as defined by NCCLS.


One month later he was readmitted with a nonproductive cough and low fever. A computerized tomogram (CT) scan of the thorax revealed a new cavitating process in the right middle lobe, abscess formation and recent infiltrates in the right lower lobe and left upper lobe (Figure 1). R. equi was again isolated from BAL cultures. Intravenous combination therapy with vancomycin 1 g twice-daily, rifampicin 600 mg twice-daily and erythromycin 1 g three times daily was instituted. A control CT scan showed some resolution of the abscess, regression of infiltrates and contraction of the cavitation. The patient was discharged after 7 weeks. Long-term prophylactic treatment with oral rifampicin 600 mg twice-daily erythromycin 1 g three times daily was continued. The patient was followed in our outpatient clinic on a monthly basis. Throughout the course of his illness the patient has proved reliable. At each clinic visit he confirmed that he had taken the drugs as prescribed. Repeated CT scans showed further regression of the infiltrates and contraction of the middle lobe cavitation (Figure 2). Four months after discharge the patient was in a good condition.

Figure 1.

Thorax CT scan (5 July 1994) showing liquefaction of a middle lobe infiltrate. There are additional smaller infiltrates in the right lower lobe and in the anterior upper left lobe.

Figure 2.

Thorax CT scan (4 October 1994) showing contraction of the lateral segment of the middle lobe, and complete resolution of the smaller infiltrates in the other segments.

Within the following month, however, he again experienced insidious onset of fatigue, non-productive cough and weight loss. However, a CT scan of the thorax showed no change. While he was still on oral antibiotic treatment, R. equi was again isolated from BAL culture. Comparative analysis of Kirby–Bauer zone sizes and MICs revealed no change in the antibiotic susceptibility pattern. Intravenous therapy with vancomycin, rifampicin and erythromycin was reinitiated, resulting in clinical improvement within 10 days. Because of the relapsing pneumonia under antimicrobial prophylaxis, surgical resection of the middle lobe was performed. The patient has now been relapse-free for more than 12 months.

R. equi is an emerging opportunistic pathogen for which the most effective therapeutic regimen remains to be established. From the first report in an AIDS patient in 1986 [2] until 1991, only 11 cases were reported [3]. Today the number exceeds 60 [1]. The clinical symptoms, fever, productive cough and pleuritic chest pain, develop very slowly and this often leads to a delay in diagnosis. Even after the correct diagnosis has been established, infections by R. equi have been notoriously difficult to treat and mortality remains high [1,4]. In vitro most R. equi isolates are susceptible to a wide range of antibiotics [4,5]. However, drug resistance as well as clinical relapse occur frequently under monotherapy and this has led to recommendations for combination therapy [1,4]. Some investigators have reported the successful antibiotic treatment of R. equi infections by combinations of imipenem and a glycopeptide [6,7]. In view of the chronic immunodeficiency in our patient, an oral prophylactic regimen that included a macrolide [8] seemed mandatory. But even the combination of erythromycin and rifampicin, which penetrates phagocytic cells, did not prevent a second relapse. This case demonstrates once more that regimens comprising erythromycin and rifampicin can be effective for treatment of the infection. However, prevention of relapse in immunocompromised patients remains a difficult task. Relapse in our case was not the consequence of acquired resistance to the administered antibiotics. Intensive follow-up care and constant alertness with regard to a relapse is needed for the management of this infection in chronically immunocompromised patients.