Table 2

Comparative clinical studies assessing the benefit of monotherapy compared with combination antibiotic therapy for infections with multidrug-resistant Gram-negative bacteria

ReferenceDesign (n)InfectionDrug combinationOutcome(s) (monotherapy vs combination therapy)Conclusion(s)
52 Prospective, randomized (53) Pseudomonas aeruginosa cystic fibrosis exacerbationsColisin (2 million IU q8h) vs colistin plus aztreonam, piperacillin, ceftazidime, imipenem, or ciprofloxacin100% vs 100% (clinical response at day 12); significant decrease in creatinine clearance in combination therapy group (nephrotoxicity)No difference in response rates; nephrotoxicity increased with combination therapy
55a Prospective, observational (162)Metallo-β-lactamase-producing Klebsiella pneumoniae bacteremiaSingle active agent vs carbapenem plus either colistin or aminoglycoside27% vs 8.3% (mortality)Patients treated with a carbapenem plus either colistin or an aminoglycoside tended to have higher survival that those treated with a single active drug
74 Retrospective (71)MDRGN infections (multiple sites)Colistin vs colistin plus meropenem85.7% vs 68.4% (clinical response); 0% vs 37% (mortality); 0% vs 7% (nephrotoxicity)No difference in response and nephrotoxicity rates; survival significantly higher in patients treated with colistin monotherapy
73 Retrospective (258)MDRGN infections (multiple sites)Colistin vs colistin plus meropenem, ampicillin-sulbactam, or piperacillin-tazobactam90% (colistin) vs 83% (colisin plus meropenem) vs 55% (colistin plus piperacillin-tazobactam or ampicillin-sulbactam) (clinical response)Favorable outcomes of MDRGN infections can be observed with colistin monotherapy or colistin in combination with meropenem
103 Retrospective (33)Carbapenem-resistant Acinetobacter baumannii Tigecycline vs tigecycline plus aminoglycoside100% (tigecycline) vs 32% (tigecycline plus aminoglycoside) (clinical failure)Improved outcomes when tigecycline was used in combination with an aminoglycoside
150 Prospective, observational (16)Carbapenem-resistant K. pneumoniae bacteremiaPolymyxin B vs polymyxin B plus tigecycline25% vs 0% (increase in polymyxin B MIC)Treatment with combination of polymyxin B and tigecycline may prevent emergence of resistance to these agents
154 Prospective, observational (23)MDR P. aeruginosa (multiple sites)Colistin (1-5 mg/kg/day) vs colistin plus amikacin or antipseudomonal β-lactam60% vs 62% (clinical response)No difference in response rates
243 Retrospective (8)MDR P. aeruginosa diabetic foot infectionsColistin (1 million IU q12h) vs colistin plus rifampin or imipenem75% vs 50% (response rates); 25% vs 0% (nephrotoxicity)No difference in response and nephrotoxicity rates