Cytomegalovirus disease recurrence after ganciclovir treatment in kidney and kidney-pancreas transplant recipients.

BACKGROUND: With the introduction of ganciclovir, the clinical pattern of cytomegalovirus (CMV) disease has changed; CMV disease recurrence after successful treatment of the initial episode has emerged as a more common problem. We studied CMV disease recurrence in kidney transplant (KTx) and simultaneous kidney-pancreas transplant (SPK) recipients, and identified risk factors for recurrence. METHODS: Between January 1987 and December 1995, of 1272 KTx and 287 SPK recipients, 332 developed CMV disease and were treated with a 14-day course of i.v. ganciclovir, followed by a 10-week course of oral acyclovir. Among these 332 recipients, 103 (31%) developed CMV disease recurrence more than 30 days after treatment for the initial episode; this group was compared with those recipients who did not develop recurrence (n=229). Risk factors examined were age, presence of diabetes, type of transplant (KTx vs. SPK), donor source (cadaver vs. living donor), treatment for acute rejection, pretransplant CMV serologic status, evidence of tissue-invasive CMV, and treatment of the initial episode with human immune globulin in addition to ganciclovir. RESULTS: Univariate analysis found that patients with recurrence were more likely to be diabetic (70.9% vs. 53.7%; P=0.04), to have undergone an SPK (39.8% vs. 20.5%; P=0.004), to have received a cadaver organ (78.6% vs. 61.6%; P=0.002), and to have received treatment for acute rejection (78.6% vs. 59.8%; P=0.001). Using multivariate analysis, two statistically significant risk factors were found: receiving a cadaver organ (relative risk [RR]=1.90; P=0.03) and treatment for acute rejection (RR=2.02; P=0.008). Diabetes (RR=1.44; P=0.18) and a cadaver SPK transplant (RR=1.55; P=0.12) tended toward increased risk for recurrence, but the difference did not reach statistical significance. The remaining variables were not significant. Interestingly, CMV recurrence did not significantly diminish 5-year graft survival (52.0% vs. 54.4%; P not significant) or patient survival (67.0% vs. 68.3%; P not significant) rates. CONCLUSIONS: CMV disease recurs in roughly one-third of KTx and SPK recipients after treatment of the initial episode with ganciclovir. A cadaver organ source and treatment for acute rejection were the most significant clinical risk factors for recurrence. Clinical predictors of recurrence such as these may help to identify those recipients who need more intensive therapeutic and prophylactic regimens.

Candida albicans and Escherichia coli are synergistic pathogens during experimental microbial peritonitis.

Candida albicans has been isolated with increasing frequency during intraabdominal infection; yet its role as a pathogen or copathogen remains controversial. A recent experimental study of its effect during polymicrobial peritonitis indicated that it did not enhance mortality when added to an Escherichia coli challenge, but that study used fecal or mucin-based adjuvants which are known to markedly potentiate the lethality of intraperitoneal bacteria. Therefore, we sought to examine the hypothesis that C. albicans and E. coli are synergistic copathogens that act in concert to increase mortality rates in experimental models of polymicrobial peritonitis, irrespective of the presence of growth adjuvant. To test this hypothesis, we assessed the mortality rates of previously healthy Swiss-Webster mice (20 g) that were challenged intraperitoneally (i.p.) with E. coli, C. albicans, or both, in either the presence or the absence of hemoglobin-mucin. In the absence of hemoglobin-mucin, E. coli plus C. albicans resulted in 83.3% mortality (P < 0.02) compared to either E. coli (0%) or C. albicans (0%) alone. In the presence of hemoglobin-mucin, the synergistic effect was not observed, lower numbers of E. coli alone (62.5%), C. albicans alone (75%), or both organisms together (100%, P > 0.05) provoked high lethality. These data demonstrate that in the absence of adjuvant, E. coli plus C. albicans provoked synergistic lethality. However, in the presence of hemoglobin-mucin the synergistic effect was no longer observed. Therefore, this study provides support for the contention that C. albicans is capable of acting as a copathogen during experimental peritonitis, but that this effect may be obscured by the presence of an adjuvant substance that itself markedly potentiates microbial growth.