1. Ensuring Quality of Care 
             
2. Optimizing Vancomycin for MRSA Infections
      
3. Selecting Appropriate Therapy for ESBL- and KPC-Producers
      
4. Dosing Strategies for MDR P. aeruginosa/A. baumannii Infections
      
5. Adjusting Antimicrobial Regimens for Efficacy and Safety
      

Dosing Strategies for MDR P. aeruginosa/A. baumannii Infections

Rising Resistance Trends

Pseudomonas aeruginosa and Acinetobacter baumannii present significant challenges when managing hospital-acquired infections.

They are among the top 6 most frequently identified organisms causing hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). [1]

Susceptibility of these pathogens to commonly used agents can vary widely and no single agent is considered highly effective. [1]

Treatment Options and Dosing Strategies

As a consequence of lower than acceptable susceptibility rates, clinicians typically utilize combination therapy when confronted with these pathogens. Selecting the optimal combination should depend on local epidemiology and based on the institutional antibiogram (or combination antibiogram, if available). [2]

Optimized dosing strategies are also recommended to maximize the PK/PD potential of antimicrobial agents. One well-studied tactic is the use of prolonged infusions of β-lactams. [3] This allows for a greater time above the MIC (T>MIC) for the dosing interval without necessarily increasing the dose administered.

References

1. Jones RN. Microbial etiologies of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. Clin Infect Dis. 2010:51(Suppl 1):S81-S87. Click here for abstract
2. Christoff J, Tolentino J, Mawdsley E, Matushek S, Pitrak D, Weber SG. Optimizing empirical antimicrobial therapy for infection due to Gram-negative pathogens in the intensive care unit: utility of a combination antibiogram. Infect Control Hosp Epidemiol. 2010;31:256-261. Click here for abstract
3. Crandon JL, Kuti JL, Jones RN, Nicolau DP. Comparison of 2002–2006 OPTAMA programs for US hospitals: focus on Gram-negative resistance. Ann Pharmacother. 2009;43:220-227. Click here for abstract

Suggested Reading
Rahal JJ. Antimicrobial resistance among and therapeutic options against Gram-negative pathogens. Clin Infect Dis. 2009;49(Suppl 1):S4-S10. Click here for complete article
This article provides an overview of resistance trends for common Gram-negative pathogens causing nosocomial infections. A review of the mechanisms of resistance to β-lactams is followed by recommended treatment strategies—combination therapy followed by de-escalation and optimized dosing by extending the infusion period for β-lactams.

Nicasio AM, Eagye KJ, Kuti EL, Nicolau DP, Kuti JL. Length of stay and hospital costs associated with a pharmacodynamic-based clinical pathway for empiric antibiotic choice for ventilator-associated pneumonia. Pharmacotherapy. 2010;30:453-462. Click here for abstract
This retrospective analysis compared ICU costs before and after a clinical pathway was implemented to optimize antibiotic regimen selection for ventilator-associated pneumonia. The clinical pathway involved using a 3-drug regimen based on local MIC distributions and a pharmacodynamically optimized dosing strategy using prolonged infusions of β-lactams. This approach resulted in a shorter length of ICU stay, shorter hospital length of stay, and lower hospital costs after VAP.

Sengstock DM, Thyagarajan R, Apalara J, Mira A, Chopra T, Kaye KS. Multidrug-resistant Acinetobacter baumannii: an emerging pathogen among older adults in community hospitals and nursing homes. Clin Infect Dis. 2010;50:1611-1616. Click here for abstract
This study describes the epidemiology, resistance patterns, and outcomes of Acinetobacter infections in older patients in community hospitals in suburban Detroit cities over a 6-year period (2003–2008). During this period, the prevalence of Acinetobacter infections increased 25%. Resistance to imipenem and ampicillin/sulbactam increased from 1.8% (2003) to 33.1% (2008). Pan-resistance (resistance to all 8 antibiotics tested) increased from 0% (2003) to 13.6% (2008). A major concern was that many patients with resistant isolates were selectively discharged to nursing homes and long-term care facilities, thereby introducing resistance in these facilities.