Treatment for UTI with Pseudomonas and VRE
For a urinary tract infection involving both Pseudomonas and VRE, treat each pathogen separately with targeted therapy: use an anti-pseudomonal agent (such as ceftazidime, cefepime, piperacillin-tazobactam, or a carbapenem based on susceptibilities) combined with fosfomycin 3g PO single dose for uncomplicated VRE UTI, or nitrofurantoin 100mg PO every 6 hours for lower tract infections. 1
VRE-Specific Treatment Approach
First-Line Options for VRE UTI
For uncomplicated urinary tract infections due to VRE, fosfomycin is FDA-approved and recommended as a single 3g oral dose. 1 This agent has demonstrated promising results in retrospective observational studies for uncomplicated VRE UTIs and shows synergistic or additive effects when combined with other agents. 1
Nitrofurantoin 100mg PO every 6 hours is an alternative first-line option for lower urinary tract VRE infections. 1, 2 Despite limited clinical data, it has good in vitro activity against VRE and has been FDA-approved since the 1950s for lower UTI treatment. 1
High-Dose Ampicillin Strategy
High-dose ampicillin (18-30g IV daily) or amoxicillin (500mg IV/PO every 8 hours) can achieve sufficient urinary concentrations to overcome ampicillin resistance in VRE UTIs. 1 A retrospective study demonstrated clinical and microbiological eradication rates of 88.1% and 86%, respectively, in patients with ampicillin-resistant VRE UTIs treated with ampicillin. 1 The high urinary concentrations of ampicillin may overcome elevated MICs and achieve necessary bactericidal activity. 1
Systemic or Complicated VRE Infections
For complicated VRE infections or bacteremia, linezolid 600mg IV or PO every 12 hours is strongly recommended. 1 Treatment duration depends on infection site and clinical response. 1
High-dose daptomycin (8-12 mg/kg IV daily) or in combination with β-lactams (penicillins, cephalosporins, or carbapenems) is recommended for VRE bacteremia. 1 A prospective observational study showed that high-dose daptomycin (9 mg/kg) combined with β-lactams significantly reduced mortality compared to monotherapy, particularly in isolates with lower daptomycin MICs (≤2 mg/L). 1
Pseudomonas-Specific Treatment Approach
Anti-Pseudomonal Agents for UTI
Treatment options for multidrug-resistant Pseudomonas UTIs include fluoroquinolones, ceftazidime, cefepime, piperacillin-tazobactam, carbapenems, aminoglycosides, ceftazidime-avibactam, and ceftolozane-tazobactam. 3, 4 Selection should be guided by local susceptibility patterns and individual patient factors. 3
For complicated UTIs caused by carbapenem-resistant Enterobacteriaceae (which may have similar resistance patterns to MDR Pseudomonas), ceftazidime-avibactam 2.5g IV every 8 hours is recommended. 1 Alternative newer agents include meropenem-vaborbactam 4g IV every 8 hours or imipenem-cilastatin-relebactam 1.25g IV every 6 hours. 1
Combination Therapy Considerations
For seriously ill patients with suspected pseudomonal infection, combination therapy improves the likelihood of including an active agent in the initial regimen. 5 While data on combination versus monotherapy remain conflicting, combination therapy has shown considerable evidence for improving adequacy of empiric therapy in severe infections. 5
Single-dose aminoglycoside is recommended for simple cystitis due to resistant organisms and as an alternative for complicated UTIs. 1 This approach minimizes toxicity while maintaining efficacy for lower tract infections. 1
Critical Clinical Considerations
Differentiate Colonization from Infection
It is essential to differentiate colonization from true infection before prescribing anti-VRE antimicrobial agents. 1 This distinction prevents unnecessary antibiotic exposure and preserves treatment options. 1
Avoid Common Pitfalls
Do not use tigecycline for VRE bacteremia due to large volume of distribution and low serum levels, despite its activity against VRE. 1 It is reserved for intra-abdominal infections. 1
Restrict fluoroquinolone use for empiric UTI treatment due to increasing resistance rates. 3 Reserve these agents for culture-directed therapy when susceptibilities confirm activity. 3
Monitor patients on nitrofurantoin for pulmonary reactions, hepatic toxicity, and gastrointestinal disturbances. 2
Antimicrobial Stewardship
Judicious antibiotic use through antimicrobial stewardship principles is essential given increasing resistance rates. 3 Knowledge of local susceptibility patterns is critical for determining appropriate empiric therapy. 3, 4
Infectious disease consultation is highly recommended for management of infections caused by multidrug-resistant organisms. 1