Mycobacterial Peritonitis in CAPD Patients in Limpopo: A 6-Year Cumulative Report from a Single Center in South Africa

Abstract

South Africa has one of the highest incidences of tuberculosis (TB) worldwide due to the ongoing human immunodeficiency virus (HIV) epidemic. There are, however, no reports on peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients due to Mycobacterium tuberculosis in South Africa. The aim of this study is to discuss our experience of tuberculous peritonitis in CAPD patients from a rural endemic area of South Africa. This is a retrospective descriptive study of CAPD patients diagnosed with mycobacterium peritonitis infection from January 2008 to August 2014 at the Limpopo Kidney and Dialysis Centre (LKDC) in South Africa. The diagnosis of peritonitis was based on the International Society for Peritoneal Dialysis (ISPD) 2010 recommendations. Peritoneal fluid samples were collected in BACTEC Myco/F Lytic Culture Vials (Becton, Dickinson and Company, Dublin, Ireland). Tenckhoff catheter tips were sent for acid-fast bacilli (AFB) smear and TB culture. Mycobacterium infection was considered in patients with clinical features of peritonitis if 1) AFB smear or TB culture was positive or 2) if the patient was smear- or culture-negative but had suggestive radiological features of TB in the lungs or abdomen or 3) if the patient improved clinically following treatment with anti-tuberculous drugs. Of 170 patients on CAPD for the period reviewed, 12 (7.1%) were diagnosed and treated for mycobacterial peritonitis. There was an equal number of males and females, and all the patients were Black Africans with a mean age of 35.4 years (17 – 51 years). Eight of the 12 patients (66.7%) had had previous episodes of non-tuberculous peritonitis. Four patients (33.3%) had elevated white blood cell count (WCC) while 9 had higher polymorph count in the PD fluid than lymphocyte count. Mycobacterial organism was confirmed in 9/12 (75%), while the diagnosis was made on clinical and radiological features in the remaining 3 patients. Seven patients (58.3%) died, 10 patients were permanently transferred to hemodialysis (HD), 1 patient returned to PD after a short stay on HD, 1 patient died after 2 years on HD due to lack of further access to dialysis, and in 1 patient, the catheter could not be removed before death. This case series corroborates findings from other previous series that mycobacterial infection in PD patients carries a high mortality and can often pose a diagnostic challenge to attending clinicians. Clinicians should have a high index of suspicion for mycobacterial peritonitis in CAPD patients with features of peritonitis who do not respond promptly to conventional anti-microbial agents. We feel that the recommendation about catheter removal during mycobacterial peritonitis should be revisited, as it had no impact on our patients' outcome.

Bacterial peritonitis is the most common infectious complication encountered in peritoneal dialysis (PD). Dialysis patients are particularly vulnerable to mycobacterial infections compared with the general population, and peritoneal tuberculosis (TB) is significant for PD patients (1). Tuberculous peritonitis is relatively uncommon in continuous ambulatory peritoneal dialysis (CAPD) patients, which may pose a diagnostic and therapeutic challenge for nephrologists. However, a high prevalence of tuberculous infection has been reported in patients undergoing CAPD, especially in areas of the world where tuberculosis is endemic (2–4). With the ongoing epidemic of human immunodeficiency virus (HIV), South Africa has one of the highest incidence rates of TB in the world according to the World Health Organization (WHO) (5). Despite this, there is scant information on mycobacterial peritonitis in patients undergoing dialysis from South Africa and indeed the entire sub-Saharan Africa region. The aim of this study is to present a descriptive report of PD patients diagnosed with and treated for mycobacterial peritonitis in a single center in a semi-urban region in South Africa.

Patients, Materials and Methods

This study was approved by the local Ethics Committee of the Pietersburg Hospital, Polokwane, in the Limpopo province of South Africa. This study had a retrospective design with the intention of describing the demographic, clinical, and biochemical features of patients identified as having mycobacterial peritonitis. Records of patients on CAPD at the Polokwane Kidney and Dialysis Centre (PKDC) were carefully assessed, and relevant information was captured in those patients who were identified as having received treatment for mycobacterial peritonitis from 1 January 2008 to 31 August 2014.

In the first instance, as the clinical features of bacterial and mycobacterial peritonitis may be indistinguishable, a presumptive diagnosis of bacterial peritonitis was made, and treatment was initiated if a patient on CAPD presented with typical clinical features (i.e. fever, abdominal pain, vomiting) or if there was a cloudy PD effluent observed or an effluent cell count with white blood cells (WBC) greater than 100/μL (after a dwell time of at least 2 hours), with at least 50% polymorphonuclear neutrophilic cells.

However, in the event of refractory peritonitis, (failure to respond to antibiotic therapy [cefazolin and ceftazidime or gentamycin for anuric patients] within 5 days of commencing) the Tenckhoff catheter should be removed and sent for microscopy, culture, and susceptibility for TB and fungi (6). In addition, peritoneal fluid was added to the BACTEC Myco/F Lytic Culture Vials (Becton, Dickinson and Company, Dublin, Ireland) for culture of Mycobacterium. The diagnosis of mycobacterial peritonitis was therefore made if acid fast bacilli (AFB) were observed or if culture for Mycobacterium species was positive or if a patient with culture-negative peritonitis and other features in support of tuberculosis did not exhibit a clinical response after sufficient duration of intra-peritoneal antibiotics. The radiological features included chest x-ray (CXR) features of TB (pleural effusion, reticulo-nodular infiltrates, miliary pattern, or cavities) and abdominal ultrasound features such as trabeculated fluid collections, para-aortic lymph node swellings, or micro-abscesses in the organs. The treatment for tuberculosis largely followed national guidelines with respect to renal dose adjustments (7). Due to the finding of a patient with a transitory blindness (patient #2) in 2010, the regime was modified to 4 single oral drugs (rifampicin, isoniazid, pyrazinamide, ethambutol), with renal dosage corrections for ethambutol and pyrazinamide, for an overall duration of 9 months using the latest protocol. There were no patients found to have significant drug toxicity after modification of the initial regime. None of the patients reported previous TB treatment.

General Characteristics of the Population in the Study

There were 170 patients on CAPD for the period reviewed (January 2008 to August 2014). Twelve (7.1%) were diagnosed with and treated for mycobacterial peritonitis. Table 1 shows the baseline demographic and clinical features of patients with mycobacterial peritonitis. All the patients were of Black African ancestry and all presented with abdominal pain and cloudy PD effluent. There was an equal distribution of males and females, with an average age of 35.4 years (17 – 51 years) and a mean duration on PD of 21.6 months (2.5 – 69.8 months). Hypertension was the commonest known cause of ESRD, in 4/12 (33.3%) patients. Eight patients (66.7%) had had multiple episodes of peritonitis before the current episode, with an average of 2.4 episodes of peritonitis (1 – 6 episodes) for all the patients.

TABLE 1.

Demographic and Clinical Features of Patients with Mycobacterial Peritonitis

Diagnosis of Mycobacterial Peritonitis

Table 2 summarizes important biochemical features obtained from analysis of the PD effluent and blood of the patients at the time of presentation. The white cell count (WCC) in the blood was elevated in only 4 patients (#4, #7, #8, and #9) while C-reactive protein (CRP) was high in all the patients who had it done. One patient (#7) with markedly elevated CRP and WCC had 0 cell counts for polymorphs, lymphocytes, and red cells in the PD fluid. Only patient #4 grew Staphylococcus cohnii from the bacterial culture of the PD fluid; other patients had negative growth after sufficient incubation time. Table 3 shows how the diagnosis of mycobacterial peritonitis was made in the 12 patients using a combination of radiological and microbiological features. Only in patients #3, #7, and #10 was the diagnosis made using a single modality. Mycobacterium tuberculosis complex (MTC) was identified in the PD fluid culture of 5/12 (41.7%) patients. Patient #2 had positive ultrasound features of TB and also grew mycobacterium avium complex on a culture of the catheter tip. In 2 patients (#5 and #11), the diagnosis was made clinically, radiologically, and from fluid and catheter tip culture.

TABLE 2.

Biochemical Features of Patients with Mycobacterial Peritonitis

TABLE 3.

Method of Diagnosis of Mycobacterial Peritonitis

Patient and Catheter Outcomes

Seven patients (58.3%) died during treatment (Table 4). One of the 7 (#12) died from lack of access to further dialysis 2 years after removal of the PD catheter. In addition, this patient did not agree to come back to the CAPD program. The others died from Mycobacterium peritonitis. The Tenckhoff catheter could not be removed from 1 patient (#7) due to her unwillingness to consent to the procedure, as there was an apparent improvement of the abdominal symptomatology despite a gradual general deterioration and wasting syndrome; otherwise, all the other patients had the catheter removed. Ten of the patients (83.3%) were transferred to hemodialysis. All the patients also received oral treatment for TB according to the National Guidelines in South Africa, but this was modified in 2010. The treatment records for patient #1 could not be found, although she acknowledged that she had received therapy for TB. Also, the average time to initiation of anti-tuberculous medications was shorter in those who did not die (21.8 [3 – 41] days) than in those who died (33.4 [6 – 69] days) (Table 1).

TABLE 4.

Patient and Catheter Outcome

Discussion

Our study shows that TB peritonitis carries a high mortality rate in patients on PD even when they are treated for the infection. Tuberculosis is often associated with increased mortality—the WHO reported that, in 2012, the 8.6 million new cases of TB worldwide caused 1.3 million deaths (5). Our finding of high mortality rate in this group of patients might therefore not be surprising, given that TB alone was responsible for 10.7% of all deaths in South Africa and was the leading cause of death in South Africa for the 3 consecutive years preceding 2011 (8). Patients with end-stage renal disease develop decreased systemic cellular immunity for a variety of reasons (9) and are therefore at increased risk of developing opportunistic infections such as tuberculosis. Talwani et al., in a review of the literature on 52 cases of TB peritonitis from different countries, found that there were 13/52 (25%) deaths in all but only 8/52 (15.4%) attributable to the infection (10). Data on PD from South Africa, which has one of the highest incidences of TB reported worldwide due to the HIV epidemic, are lacking. This is therefore an important study from this country. Although there are several reports on mycobacterial peritonitis, most of these reports have come from countries with a far lower incidence of TB than South Africa (reviewed extensively in Talwani et al.) (10) and there are no data from anywhere on the African continent.

Our study also confirms that the diagnosis of mycobacterial peritonitis can be difficult and that cellular counts in the blood and dialysate fluid may be misleading. In our study, 8/12 patients (66.7%) had normal WCC in blood, and 9/11 patients (81.8%) had more polymorphonuclear white cells, the latter possibly suggesting a bacterial infection. Although CRP was elevated in all those tested, we suspect this would also be the case in other forms of peritonitis. Mycobacterium was isolated only in 9/12 (75%) patients; in the other 25%, the diagnosis of mycobacterial peritonitis was made from radiological features (chest X ray and abdominal ultrasound scan) of TB in the lungs or the abdomen. Vadivel et al. (11), in a case report of a CAPD patient with TB-peritonitis, described the diagnostic perplexity often encountered in making a diagnosis of TB-peritonitis and its associated high mortality in the PD population. They suggested a high degree of suspicion and an aggressive diagnostic approach, including the use of laparoscopic visualization, peritoneal biopsy, and molecular diagnostic tools. Only in 5/12 patients (41.7%) were we able to isolate mycobacterial organism from the PD fluid. Abraham et al. (12) have also emphasized the difficulties encountered in making a diagnosis, all the patients in their report having a negative Mantoux test, and they resorted to a combination of microbiological and radiological assessments to make the diagnosis.

Given the diagnostic challenges, we employed a combination of biochemical, microbiological, and radiological assessments to make the diagnosis of mycobacterial peritonitis in our patients. As shown in Table 3, only in 2 patients (#7 and #10) was the diagnosis made using a single parameter that did not isolate the organism. Waness et al. also published a report in which the diagnosis was made from clinical features alone in one of their patients who remained culture-negative but responded to anti-tuberculous treatment (13). We therefore think that with a high index of suspicion, in CAPD patients who remain culture-negative and unresponsive to routine anti-microbial agents, treatment for tuberculosis should be considered.

We are uncertain what role a delay in initiating treatment could play in contributing to our patients' outcome, as those who died had a longer time to TB drug treatment initiation than those who lived (Table 1). We believe that in all patients who are culture-negative and non-responsive to conventional treatment or culture-positive with intractable peritonitis, samples must be cultured for Mycobacterium. In addition, we support that CXR evaluations and abdominal ultrasound should be part of the work-up for peritonitis. In cases where abnormalities are found on an abdominal ultrasound or CXR, samples for Mycobacterium infections must be included, regardless of the clinical outcome to the antibiotics management and bacterial culture.

Bacterial peritonitis has been reported by some authors as coexisting with tuberculous peritonitis (12). We therefore think that in some patients with culture-positive bacteria exhibiting slow recovery from peritonitis, Mycobacterium may be present in a latent phase. Our report supports this, as demonstrated by patients #7 and #8, who were apparently successfully treated for peritonitis but relapsed within 4 weeks of completion of antibiotics. Although the International Society for Peritoneal Dialysis (ISPD) guidelines on catheter removal recommend its consideration in mycobacterial infection (6), some authors have treated their patients without catheter removal and suggested that removal of the Tenckhoff catheter is not mandatory in the management of TB-peritonitis complicating CAPD (14). The catheter was removed in all but 1 of our patients (#7), who did not give consent for the procedure. Removal of the catheter made no difference to our patients' outcome, and this guideline may need to be reviewed. However, removing the catheter could be useful in diagnosis (isolation of the organism), as we found that that catheter tip sent for TB culture had a good yield (Table 3).

There is need for clarity from the guidelines on how TB-related peritonitis should be managed. Bhowmik et al. (15) recently raised concerns regarding ethambutol not being recommended by ISPD guidelines, and they suggested dose adjustments in renal patients. Our study supports the observation that ethambutol should not be absolutely contraindicated.

Conclusion

In conclusion, our case series corroborates the findings from previous series that mycobacterial infection in PD patients carries a high mortality and can often pose a diagnostic challenge to attending clinicians. Clinicians should have a high index of suspicion for mycobacterial peritonitis in CAPD patients with features of peritonitis who do not respond promptly to conventional anti-microbial agents. We feel the recommendation about catheter removal during mycobacterial peritonitis should be revisited.

Disclosures

The authors have no financial conflicts of interest to declare.