Risk of recurrent non-typhoid Salmonella bacteraemia after early discontinuation of ciprofloxacin as secondary prophylaxis in AIDS patients in the era of highly active antiretroviral therapy
Journal
AIDS
Journal Volume
15
Journal Issue
5
Pages
645-647
Date Issued
2001
Author(s)
Abstract
Bacteraemia caused by non-typhoid Salmonella (NTS) is not an uncommon opportunistic infection in patients with HIV infection and AIDS worldwide. It has been one of the leading aetiologies of the community-acquired bacteraemia of AIDS patients in African countries [1], western countries [2], and Taiwan [3]. NTS bacteraemia in AIDS patients may recur [4,5] and, in fact, recurrent NTS bacteraemia is one of the diagnostic criteria of AIDS [6]. In order to prevent recurrences, prolonged antibacterial prophylaxis with ciprofloxacin, preferably for 6–8 months, has been recommended by the experts [7], the US Public Health Services (USPHS) and the Infectious Disease Society of America (IDSA) [8]. With the introduction of highly active antiretroviral therapy (HAART) and the reconstitution of immunity, the incidences of several major opportunistic diseases decreased significantly [9,10], and primary and secondary prophylaxis against several opportunistic infections, such as Pneumocystis carinii pneumonia [11,12] and disseminated Mycobacterium avium complex infection [13], may be discontinued in patients responding to combination antiretroviral therapy. However, the optimal duration of secondary ciprofloxacin prophylaxis against NTS bacteraemic recurrences had not been investigated by clinical studies despite the USPHS/IDSA recommendations. In this study, we aimed to evaluate whether the duration of secondary prophylaxis with ciprofloxacin against recurrent NTS bacteraemia might be shortened in HIV-infected patients after the start of HAART. A prospective study had been conducted at National Taiwan University Hospital, the largest referral hospital for the management of HIV-related complications in Taiwan, to describe the clinical spectrum and impact of HAART on HIV infection [14]. Since the initiation of HAART, we started to assess the impact of HAART on the recurrence of NTS bacteraemia by the discontinuation of ciprofloxacin as secondary prophylaxis one month after concurrent HAART and ciprofloxacin therapy. From 24 June 1994 to 30 September 2000, 31 out of 461 non-haemophiliac patients (6.7%) with HIV infection developed 38 episodes of NTS bacteraemia: two patients with three episodes, three with two episodes, and 26 with one episode. For patients diagnosed with NTS bacteraemia, ceftriaxone was administered at a dose of 1.0 g every 12 h. for 10–14 days before switching to oral ciprofloxacin at a dose of 500 mg every 12 h as secondary prophylaxis, which was usually continued lifelong at the National Taiwan University Hospital, before the introduction of HAART into Taiwan on 1 April 1997 [14]. Because all of the 31 patients had had a CD4 cell count of less than 200 × 106/l, trimethoprim–sulfamethoxazole was continued for P. carinii pneumonia prophylaxis. Ciprofloxacin was chosen because of good in-vitro activity (90% minimum inhibitory concentration, 0.75 μg/ml) against the Salmonella isolates at this hospital [3]. Consecutive case patients developing NTS bacteraemia between 24 June 1994 and 31 March 1997 (period 1) constituted a historical control group that was compared with the patients between 1 April 1997 and 30 September 2000 (period 2). The patients of period 1 were censored at the time of death or loss to follow-up, or 31 March 1997. Patients surviving beyond 31 March 1997 and enrolled after 1 April 1997 were enrolled into period 2, and were censored at the time of death or loss to follow-up, or 30 September 2000. All of the 31 patients with NTS bacteraemia diagnosed over the past 6 years were at the advanced stage of HIV infection (Centers for Disease Control and Prevention classification C3), with a median CD4 lymphocyte count of 8 × 106/l (range 1–187 × 106/l): 17 being newly diagnosed with HIV infection, and 22 naive to any antiretroviral therapy. NTS bacteraemia was the presenting opportunistic disease of AIDS in 22 patients. The clinical characteristics of the 31 patients with 38 episodes of NTS bacteraemia developing during the two time periods, 23 episodes in period 1 and 15 in period 2, are shown in Table 1. The baseline characteristics of the two cohorts were similar, except that more patients in period 2 were naive to antiretroviral therapy.Table 1: Characteristics of 31 HIV-infected patients with non-typhoid Salmonella bacteraemia in two time periods. During period 1, five out of 16 patients developed recurrent NTS bactaeremia, whereas during period 2, none out of 15 had recurrences (P = 0.043 by Fisher's exact test). The seven episodes of recurrent NTS bacteraemia all occurred during period 1, whereas no recurrence was diagnosed during period 2. The four patients enrolled in period 1 and continued to be observed in period 2 had had no recurrences after the initiation of HAART. The total observation duration of period 1 was 6.94 patient-years and that of period 2 was 15.47 patient-years. Compared with the NTS bacteraemic recurrence rate of 100.86 per 100 patient-years during period 1 [95% confidence interval (CI) 93.53, 108.62], the recurrence rate was zero per 100 patient-years during period 2 (95% CI, 0, 0.2384) (Table 1). The isolates causing recurrent bacteraemia was typed using the method described previously [15], and were shown to be identical in each individual (data not shown). The isolates tested during period 1 did not demonstrate resistance to ciprofloxacin whereas one isolate during period 2 was resistant to ciprofloxacin using the disk susceptibility test. Six patients in period 1 had NTS isolates resistant to trimethoprim–sulfamethoxazole whereas four patients in period 2 had such isolates (P = 0.704). As of 30 September, nine deaths and three losses to follow-up occurred during period 1. The deaths were attributed to lymphoma (two), disseminated M. avium complex infection (two), sepsis of undetermined aetiology (two), cytomegalovirus disease (one), penicilliosis marneffei (one), and aspergillosis (one). Five deaths, but no loss to follow-up, occurred during period 2. The deaths were attributed to acute myocardial infarction (one), concurrent cryptococcosis and penicilliosis marneffei (one), brain tumour of undetermined aetiology (one), pulmonary aspergillosis (one), and Kaposi's sarcoma (one). In earlier reports, recurrences of NTS bacteraemia developed in patients without HAART, despite the fact that they continued prophylactic chemotherapy of good in-vitro activity [4,5]. Our report showed that the risk of recurrent NTS bacteraemia decreased significantly with the introduction of HAART between the two patient cohorts, consisting of similarly immunosuppressed HIV-infected patients in two time periods. The finding of no NTS bacteraemic recurrence after the early discontinuation of ciprofloxacin prophylaxis after the initiation of HAART suggested that the duration of ciprofloxacin prophylaxis, instead of 6 months, might be shortened. However, our study was limited by the fact that it was not a randomized study and the sample size was small. Further randomized control studies are needed to define the optimal duration of secondary ciprofloxacin prophylaxis against NTS bacteraemic recurrences. Chien-Ching Hungab Szu-Min Hsieha Chin-Fu Hsiaoc Mao-Yuan Chena Wang-Hwei Shenga
SDGs
Other Subjects
antiretrovirus agent; ceftriaxone; ciprofloxacin; cotrimoxazole; acquired immune deficiency syndrome; adult; aged; antibiotic prophylaxis; article; bacteremia; bacterium isolate; clinical article; clinical trial; controlled clinical trial; controlled study; female; human; male; Pneumocystis pneumonia; priority journal; recurrence risk; recurrent disease; Salmonella; virus load; Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antibiotic Prophylaxis; Antiretroviral Therapy, Highly Active; Bacteremia; Ciprofloxacin; Female; Humans; Male; Middle Aged; Prospective Studies; Recurrence; Risk Factors; Salmonella Infections
Type
journal article