Ciprofloxacin Treatment of Bacterial Peritonitis Associated with Chronic Ambulatory Peritoneal Dialysis Caused by Neisseria cinerea

Abstract

Bacterial peritonitis is a well-recognized complication of chronic ambulatory peritoneal dialysis (CAPD) in patients with end-stage renal failure. We present a case of peritonitis due to an unusual pathogen, Neisseria cinerea, unresponsive to the standard intraperitoneal (i.p.) vancomycin and gentamicin, which responded rapidly to oral ciprofloxacin.

CASE REPORT

At the end of December 2005, a 38-year-old man with end-stage renal failure, managed with CAPD for 2.5 years, was admitted with diarrhea, severe abdominal pain, and cloudy peritoneal dialysis fluid. The patient was an insulin-dependent diabetic with a number of complications other than renal failure. These included peripheral and autonomic neuropathy, ischemic heart disease, and two previous myocardial infarctions. He had had one previous episode of peritonitis 1.5 years prior to this admission, although no organism was isolated at the time. At the time of admission, he was taking flucloxacillin orally at a dose of 500 mg four times daily for an infected foot ulcer.

He was admitted to the hospital because of a 2-day history of diarrhea and a 1-day history of severe abdominal pain with nausea and vomiting. He recognized the cloudy dialysis fluid and diagnosed himself with peritonitis. On examination, he was afebrile, with a diffusely tender abdomen. The exit site of the peritoneal dialysis cannula was not inflamed. Investigations revealed a dialysis fluid cell count of 2,582 white blood cells per μl and 96% polymorphs but with no organisms seen on the Gram stain of a spun deposit and a C-reactive protein (CRP) level that was elevated at 135 mg/liter.

His empirical treatment was a standard regimen of i.p. vancomycin (2 g) on day 1 and gentamicin (40 mg) in the last peritoneal fluid exchange of each day. However, 2 days after initiating treatment he remained unwell with a tender abdomen and his CRP level had risen further to 314 mg/liter. At this stage, the microbiology laboratory reported that a Neisseria species had been isolated from his initial dialysis fluid and treatment with ciprofloxacin (500 mg orally twice daily) was commenced. His i.p. vancomycin was stopped, but the gentamicin was continued. Within 24 h, his symptoms had improved and his CRP level and peritoneal dialysis fluid cell count declined over the succeeding days. He completed a course of oral ciprofloxacin and i.p. gentamicin for 10 days with full recovery from peritonitis.

A spun deposit of the admission sample of cloudy dialysate had been cultured on blood and chocolate agar in an atmosphere with increased carbon dioxide, and a further sample of the unspun fluid had been injected into standard blood culture bottles (BacT/Alert; bioMérieux, Basingstoke, United Kingdom). Direct culture plates were negative after 48 h of incubation, but the fluid inoculated into the blood culture bottles yielded an oxidase-positive, gram-negative diplococcus. The isolate was identified as N. cinerea on the basis of biochemical testing (API/NH; bioMérieux, Basingstoke, United Kingdom) and 16S rRNA gene sequencing. The isolate was susceptible to ciprofloxacin (MIC, 0.012 mg/liter by E test [BioStat, Stockport, United Kingdom]) but resistant to vancomycin (MIC, >256 mg/liter). The gentamicin MIC was 1 mg/liter, and the oxacillin MIC was 24 mg/liter.

N. cinerea is generally considered a nonpathogenic organism that is a common nasal and oropharyngeal commensal (9). There are rare reports of its causing tonsillitis, lymphadenitis (2), and proctitis (4). A patient with systemic lupus erythematosus was reported as having had N. cinerea causing CAPD-associated peritonitis on two separate occasions (5, 6). Other Neisseria species have caused CAPD-associated peritonitis, as summarized in Table 1. In most of these reports, the peritonitis failed to respond to the standard empirical therapy of i.p. vancomycin and gentamicin (7). In three cases, therapy with a fluoroquinolone was effective, as in the present case. In this case, although the gentamicin MIC for the organism was 1 mg/liter, the patient failed to respond to the initial i.p. therapy, perhaps because of the poor intracellular penetration of gentamicin.

TABLE 1.

Case reports and outcomes of Neisseria peritonitis associated with CAPD

Neisseria sp.	Yr	Initial antimicrobial(s)	Eventual antimicrobial(s)	Outcome	Reference
N. cinerea	1994	Vancomycin (i.p.), tobramycin (i.p.)	Ciprofloxacin (i.p.), ceftriaxone (i.v.)a	Cure	6
N. cinerea	1996	Vancomycin (i.p.), gentamicin (i.p.)	Vancomycin (i.p.)	Cure	5
N. cinerea	2006	Vancomycin (i.p.), gentamicin (i.p.)	Ciprofloxacin (oral), gentamicin (i.p.)	Cure	This report
N. meningitidis	1995	Vancomycin (i.p.), gentamicin (i.p.)	Ceftriaxone (i.v.), ciprofloxacin (i.v.)	Death	8
N. meningitidis	1998	Vancomycin (i.p.)	Penicillin (oral)	Cure	3
N. mucosa	1993	Vancomycin (i.p.), ceftazidime (i.p.)	Vancomycin (i.p.), ceftazidime (i.p.)	Cure	12
N. mucosa	2003	Cefazolin (i.p.), tobramycin (i.p.)	Ceftriaxone (i.p.)		11
N. mucosa	2005	Cephalothin (i.p.), gentamicin (i.p.)	Ceftriaxone (i.p.)	Cure	14
N. sicca	1994	Vancomycin (i.p.)	Ceftazidime (i.p.)	Cure	13
N. sicca	2001	None	Levofloxacin	Cure	10
N. subflava biovar perflava	1999	Cotrimoxazole (oral)	Ceftazidime (i.p.)	Cure	15

^ai.v., intravenous.

Currently, around 5 to 10% of CAPD-associated peritonitis is culture negative (1) and fastidious organisms such as Neisseria species may contribute to this value. While some do respond to a combination of vancomycin and gentamicin, the lack of response to standard first-line i.p. therapy should alert clinicians to the possibility of a rarer cause of peritonitis, in this case an oropharyngeal organism. Oral ciprofloxacin is a simple and well-tolerated antimicrobial that could be considered a useful addition to empirical therapy under these circumstances.