Evolution of Antibiotic Resistance Mechanisms and their Relevance to Dialysis-Related Infections

As the survival of patients with end-stage renal failure has improved, their exposure to antibiotics has also increased. Infections, especially peritoneal dialysis–related peritonitis, are unavoidable because of lapses in technique and the slow worsening of systemic and peritoneal defense associated with aging and dialysis. The selective pressure inherent in the use of antibiotics shapes the pattern of antibiotic resistance in the bacteria causing peritonitis and extraperitoneal infections, and vice versa.

Renal function–preserving and non-ototoxic regimens that incorporate double β-lactams (first- and third-generation cephalosporins) for peritonitis have increased the selective pressure in favor of methicillin-resistant staphylococci (MRS) and extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae. Attempts to use the fluoroquinolones as alternatives to β-lactams was met with rocketing quinolone resistance. The high incidence of MRS led many nephrologists to use empiric vancomycin—until the début of vancomycin-resistant enterococci. The recent emergence of heterogeneous and high-level vancomycin resistance in staphylococci (which are especially prevalent in patients on dialysis) calls for further prudence in the use of vancomycin.

The coming challenges are ESBL-producing Enterobacteriaceae with carbapenemase, multi-resistant Pseudomonas, and highly virulent community-acquired methicillin-resistant Staphylococcus aureus with Panton–Valentine leukocidin. Antibiotic auditing programs and meticulous patient training by nurses are the only available defense at the moment. Novel approaches such as antibiotic-impregnated Tenckhoff catheters, biocompatible dialysis fluid, and peritoneal immuno-augmentation strategies are eagerly awaited.