Incidence and clinical significance of nasal and pericatheter colonization by Gram-negative bacteria among patients undergoing chronic peritoneal dialysis
Miguel Pérez-Fontán1,,
Ana Rodríguez-Carmona1,
Miguel Rosales2,
Teresa García-Falcón1 and
Francisco Valdés1
1 Divisions of Nephrology and
2 Public Health, Hospital Juan Canalejo, A Coruña, Spain
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Abstract
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Background. Nasal and pericatheter colonization by Staphylococcus aureus portends an increased risk of peritonitis and exit-site infection for peritoneal dialysis (PD) patients. The aim of the present study was to examine the incidence of colonization by other peritoneal pathogens, and more specifically by Gram-negative bacteria (GNB), among PD patients, and to disclose its potential correlation with PD-related infections.
Method. Over a 3-year period, we prospectively screened 152 PD patients and 99 partners every other month for nasal and pericatheter bacterial colonization (total follow-up for patients 3182 months). We performed 1089 studies in patients and 561 in partners.
Results. Although S. aureus and coagulase-negative Staphylococcus spp. predominated both in patients and partners, we recovered GNB from 15.8% (nares) and 22.4% (pericatheter) of the patients and from 29.3% of the partners. Most isolations of GNB were transient and only 7.2% of the patients and 7.1% of the partners had the same GNB isolated in at least two controls from the same sampling site. Older age, male gender, longer follow-up on PD, previous immunosuppressive therapy, low socioeconomic conditions, and a high global incidence of peritonitis were predictive of colonization by GNB. Previous pericatheter mupirocin therapy was also associated with later colonization by GNB. Nasal or pericatheter colonization by bacteria other than S. aureus, particularly GNB, had a poor predictive power for PD-related infections.
Conclusion. Nasal and pericatheter bacterial colonization is protean in PD patients and their partners, and includes the significant presence of potentially pathogenic GNB. Colonization by GNB was not clearly associated with an increased risk of peritonitis or exit-site infection in these patients.
Keywords: exit-site infection; Gram-negative bacteria; nasal carriage; pericatheter colonization; peritoneal dialysis; peritonitis
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Introduction
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Peritonitis and exit-site infection (ESI) still represent important concerns for peritoneal dialysis (PD) patients, on a day-to-day basis. Moreover, an efficient prevention of these infections has a significant impact on the global results of PD therapy [1]. It is widely accepted that effective treatment of nasal and pericatheter colonization by Staphylococcus aureus has a positive effect on the incidence of PD-related peritonitis and ESI by the same bacteria [2,3]. On the contrary, attempts to correlate infections by coagulase-negative Staphylococcus spp. (CNS) with nasal or skin colonization by the same bacteria have been generally unsuccessful [4,5]. Information on the prevalence of colonization by other bacteria, and more specifically by pathogenic Gram-negative bacteria (GNB), is notably limited in PD patients. Nasal and skin flora have been widely studied in the general population [6,7], and also in subsets like immunocompromised [8] and haemodialysis patients [9,10] and health personnel [9,11], but no such studies appear to have been carried out in PD patients and their partners, to our knowledge. As a consequence, the correlation between asymptomatic colonization by GNB and PD-related infections has been also insufficiently studied.
We have performed a 3-year prospective study on our patients undergoing home PD and their active dialysis partners, with the aims of establishing the spectrum and incidence of bacterial colonization by GNB affecting the nares and the pericatheter area, and also disclosing a potential correlation with peritonitis and ESIs by the same agents.
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Subjects and methods
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The study population included all patients and their active family partners undergoing PD in our centre between 1 September, 1997 and 31 October, 2000. Following a prospective design, we screened every other month the nasal (patients and partners) and/or pericatheter (patients) bacterial flora, with a specific focus on the identification of GNB. Nasal and pericatheter swabs were plated in standard bacterial media (blood agar, Macconkey, mannitol salt agar, and thioglycollate broth) at 35°C for 48 h. In case of bacterial growth, subcultures in blood agar and Macconkey's media were performed. Species identification was carried out using the Pasco system (Difco). Growth of <5 colonies per plate was considered non-significant.
The study was partially interventional because nasal or pericatheter isolation of S. aureus was systematically treated with 2% mupirocin ointment, following reported schedules [2,3]. Also, pericatheter (but not nasal) isolation of GNB was followed by treatment with ciprofloxacin (3 mg/ml solution) or gentamycin (3 mg/g ointment), once a day over 3 weeks, but only in the presence of an equivocal (mild erythema or serous exudation) exit-site. Patent ESI was treated both with local and systemic antibiotic therapy. Pericatheter isolations were not considered for analysis in this study in the presence of a clinical diagnosis of ESI.
We collected information on all the isolations obtained during the study period, and correlated these findings with the episodes of peritonitis and ESI observed during the same period. Peritonitis and ESI were defined according to standard criteria [12,13].
Comparison between variables was based on Student's t-test, Wilcoxon's test and
2 analysis. The SPSS 10.0 software was used for statistical analysis.
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Results
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The study population included 152 patients and 99 active dialysis partners. The patient population was composed of 91 men (59.9%) and 61 women (40.1%), with a mean age of 59 years (range 884). The spectrum of renal diseases was standard, including 50 diabetics (32.9%). Seventy-one patients (46.7%) were treated with continuous ambulatory peritoneal dialysis (CAPD) and 81 (53.3%) with automated PD. Seventy-four patients (40.7%) were totally or partially unable to perform self-dialysis, and 58 (38.2%) were considered to have a low socioeconomic status. Total follow-up during the study period was 3186 patient-months (range 238).
We performed 1089 cultures in patients (range 220), and 561 in partners (range 119). A total of 410 nasal (37.6%) and 630 (57.8%) pericatheter studies were considered negative or non-significant; also 225 studies in partners (40.1%). The mean numbers of positive isolations were 4.5 (range 015) (nares, patients), 3.0 (range 015) (pericatheter, patients), and 3.4 (range 011) (nares, partners), respectively.
Staphylococcus aureus and CNS were highly predominant, both in patients and partners (Table 1
), but GNB were also frequently isolated (Table 2
). Twenty-four patients (15.8%) had at least one GNB isolated from the nares (range 17) and 34 (22.4%) from the pericatheter area (range 113); 29 partners (29.3%) had at least one GNB nasal isolation (range 17). Enterobacteriaceae were very predominant amongst colonizing GNB (Table 2
). In general, colonizations were transient; only six patients (3.9%) (nares), seven patients (4.6%) (pericatheter), and seven partners (7.1%) had the same GNB isolated in at least two controls from the same screening point.
When a patient had an isolation of a GNB from the nares, he/she was also more likely to have an isolation of a GNB from the pericatheter area (58.3 vs 15.6%, P<0.001). Patients presenting at least one isolation of a GNB from the nares or the pericatheter area were older (63.7 vs 57.1 years, P=0.01), more likely male (75.0 vs 53.7%, P=0.015), had been treated more frequently with steroids or immunosuppressive therapy for renal transplant or systemic disease (8.8 vs 1.7%, P=0.04), had a longer follow-up on PD at the end of their participation in the study (37.6 vs 22.1 months, P=0.001) and a higher global incidence of peritonitis (0.67 vs 0.38 episodes/patient/year, P=0.03), and came more frequently from a low socioeconomic setting (50.0 vs 33.3%, P=0.04) than their counterparts not presenting this complication. On the contrary, we found no correlation between colonization by GNB and diabetes, mode of PD, or hospital admission rate. Alternatively, patients treated with pericatheter mupirocin for S. aureus colonization had an increased accumulated incidence of isolation of GNB from the pericatheter area, when compared with non carriers of S. aureus (34.0 vs 16.7%, P=0.01); on the contrary, treatment with intranasal mupirocin was not associated with an increased risk of nasal colonization by GNB (13.0 vs 18.1%, P=0.37). Finally, we found a trend to an association in the isolation of GNB from patients unable to perform self-dialysis and their active partners (41.2% of partners positive for GNB if GNB isolated from patient vs 23.1% if GNB not isolated from patient, P=0.06).
During the study period, we observed 146 episodes of peritonitis (0.55 episodes/patient/year) and 49 episodes of ESI (0.18 episodes/patient/year). Two out of three peritonitis by S. aureus were associated with S. aureus nasal carriage (both patient and partner). Twenty-one patients suffered 23 episodes of ESI by S. aureus; 19 of these episodes (82.3%) were associated with nasal carriage of S. aureus by the patient or his/her partner and, in 10 cases (43.5%), S. aureus had been isolated from the pericatheter area before the ESI was diagnosed.
At least one GNB bacteria was isolated in 44 episodes of peritonitis (30.1%) and 13 of ESI (26.5%). The aetiologic spectrum of PD-related infections is presented in Table 3
. Table 4
depicts the matches observed between nasal or pericatheter isolations and later infections. Only 9.1% of the peritonitis by GNB were associated with previous nasal or pericatheter isolation of the same bacteria. Moreover, after excluding from analysis eight episodes of polymicrobial, patently intestinal peritonitis, this figure increased only to 11.1%. The correlation was better for ESI, and five episodes by GNB (38.5%) could be predicted from screening studies. However, seven isolations of GNB were treated with local ciprofloxacin (n=6) or gentamycin (n=1) in the presence of an equivocal exit site, and only one of these cases progressed to frank ESI. As a whole, the positive predictive value for one single isolation of a GNB from the nares (patient or partner) was 9.8% for peritonitis and 7.7% for ESI; the corresponding values for one isolation form the pericatheter area were 9.4 (peritonitis) and 30.8% (ESI). When the same GNB was isolated at least twice from the nares (patient or partner), the positive predictive value was 18.2% (2/11) for peritonitis and 0% (0/11) for ESI; the corresponding values in case of two or more isolations of the same GNB from the pericatheter area were 0% (0/7) for peritonitis and 28.6% (2/7) for ESI.
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Discussion
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Colonization is defined as the presence of a microorganism in or on a host, with growth and multiplication, but without any overt clinical expression or detected immune reaction in the host at the time the microorganism is isolated [14]. Normal skin flora is normally dominated by relatively few species, with a predominance of Gram-positive bacteria, like Staphylococcus spp., Micrococcus spp., and coryneforms. Acinetobacter spp. are the only group of GNB regularly colonizing the skin [15]. Pathogenic GNB like Proteus spp., Pseudomona spp., Enterobacter spp., and Klebsiella spp. colonize the normal skin and the nares rarely [7], but can be recovered in significant amounts from specific zones, like the vulva, the perineum, the toe clefts, or the external auditory meatus [15]. Many factors influence normal skin flora. First, there are some idiosyncratic variations from subject to subject, and in a given subject with time; seasonal variations are also frequent. Age, race and gender also appear to influence skin flora [15]. Alternatively, it is unclear if poor personal hygiene may modify qualitatively normal skin flora. Areas of dry skin display a relatively poor bacterial flora, as opposed to moist areas and those supplied by many sebaceous glands [7]. Thus, different parts of the body may show strong differences in bacterial flora, both quantitatively and qualitatively [15].
Some external factors may favour skin colonization by GNB. Topical antiseptics (if active against Gram-positive bacteria) and closed, plastic dressings (by increasing humidity) may favour the growth of GNB [15]. Systemic antibiotic therapies active against Gram-positive bacteria may also favour skin colonization by GNB. Critically ill patients display a high incidence of cutaneous colonization by GNB, to an extent that cannot be explained solely by the treatments they are receiving. Continuous contact with the hospital setting and some of the above exposed factors may explain a relatively high incidence of skin colonization by GNB among patients on haemodialysis and their health care personnel [9,10]. On the other side, the epidemiology of bacterial skin colonization has not been adequately assessed in PD patients. In our study, nasal and pericatheter skin flora were dominated by S. aureus and CNS, as expected. This not withstanding, colonization by pathogenic GNB was relatively frequent, even more so in partners than in patients, suggesting that factors like the use of antiseptics and antibiotics, and the frequent contact with the hospital setting may be determinant in the genesis of this complication. For instance, the use of povidone-iodine to cleanse the catheter exit-site has been associated with Pseudomona aeruginosa colonization and infection in patients undergoing PD [16]. Interestingly, pericatheter application of mupirocin was very effective to eradicate S. aureus, but appeared to favour colonization by GNB.
It is well known that bacterial colonization may be a harbinger of infection. Staphylococcus aureus, Candida spp., Clostridium difficile and Enterococcus spp. have received most attention, in this sense [14]. Among PD patients, the consequences of nasal and pericatheter colonization by S. aureus have been the subject of many studies. Our results confirm the well-known association between S. aureus carriage and PD-related infections [12,13], even in a setting like ours, where this condition is tightly screened and treated with mupirocin. It is presently unclear whether this treatment should be systematically administered or used only when recolonization is demonstrated. The former option may be more cost-effective [13], but the risk of S. aureus resistance to mupirocin may increase [17].
The degree of correlation between colonization, even if transient, by GNB bacteria and PD-related infections is largely unknown, pari passu with the lack of information on resident flora in PD patients and their partners. In our study, this correlation was relatively poor, although not negligible. Correcting for the fact that colonization by GNB is transient in most cases did not improve the efficiency of the screening, as repeated isolations of the same GNB from the same point did not show a good predictive value either. Pericatheter isolations showed a better predictive power than nasal isolations, especially for ESI, but we must consider the possibility that some of these isolations may have represented undiagnosed, ongoing ESI. As a whole, our results do not support the case for systematic treatment of asymptomatic nasal or pericatheter colonization by GNB, in PD patients. However, it is possible that local treatment of equivocal exit-sites with ciprofloxacin or gentamycin may have modified the natural history of pericatheter colonization. Consequently, our study does not discourage firmly an active approach to asymptomatic or equivocal pericatheter colonization by potentially aggressive GNB. In fact, GNB peritonitis developing after asymptomatic pericatheter colonization has been documented [18].
In conclusion, nasal and pericatheter bacterial colonization is protean in PD patients and their partners, and includes the significant presence of potentially pathogenic GNB. Colonization by GNB is frequently transient and does not seem to portend a significant risk of peritonitis or ESI in these patients.
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Notes
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Correspondence and offprint requests to: Dr M. Pérez Fontán, Servicio de Nefrología, Hospital Juan Canalejo, Xubias 84, E-15006 A Coruña, Spain. Email: mfontan{at}canalejo.cesga.es 
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Received for publication: 14. 4.01
Revision received 24. 8.01.