Mathematical Model To Quantify the Effects of Risk Factors on Carbapenem-Resistant Acinetobacter baumannii

ABSTRACT Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are increasing, and they are associated with an increased risk of mortality in hospitalized patients. Linear regression is commonly used to identify concurrent trends, but it cannot quantify the relationship between risk factors and resistance. We developed a model to quantify the impact of antibiotic consumption on the prevalence of CRAB over time. Data were collected from January 2007 to June 2013 from our institution. Quarterly antibiotic consumption was expressed as defined daily dose/1,000 inpatient days. Six-month prevalence of CRAB was expressed as a percentage of all nonrepeat A. baumannii isolates tested. Individual trends were identified using linear regression. Antibiotic consumption from 2007 to 2011 was input as a step function in a relationship with CRAB. Model fit was evaluated by visual inspection and the residual sum of squares. The final model was validated using the best-fit (95% confidence interval) parameter estimates and antibiotic consumption to predict CRAB prevalence from January 2012 to June 2013. Cefepime, ertapenem, and piperacillin-tazobactam consumption and CRAB prevalence increased significantly over time. CRAB prevalence was best correlated to ertapenem (use sensitive; r2 = 0.76), and accounting for additional concurrent antibiotic use did not significantly improve model fit. Prospective validation with ertapenem consumption correlated well with CRAB observations, suggesting good predicting ability of the model. Our model provided the quantitative impact of antibiotic consumption on CRAB. We plan to further refine this model to account for multiple risk factors. Interventions should focus on controlling risk factors with the highest impact on resistance.

[1]  T. Einarson,et al.  Carbapenem resistance and mortality in patients with Acinetobacter baumannii infection: systematic review and meta-analysis. , 2014, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[2]  A. Andremont,et al.  Antimicrobial agent exposure and the emergence and spread of resistant microorganisms: issues associated with study design , 2013, European Journal of Clinical Microbiology & Infectious Diseases.

[3]  Florian Hölzl,et al.  Time Series Analysis as a Tool To Predict the Impact of Antimicrobial Restriction in Antibiotic Stewardship Programs Using the Example of Multidrug-Resistant Pseudomonas aeruginosa , 2013, Antimicrobial Agents and Chemotherapy.

[4]  B. Gu,et al.  Correlation Between Carbapenem Consumption and Antimicrobial Resistance Rates of Acinetobacter baumannii in a University‐Affiliated Hospital in China , 2013, Journal of clinical pharmacology.

[5]  V. Tam,et al.  Correlation of Hospital Carbapenem Consumption and Resistance Trends in Selected Gram-Negative Bacteria , 2012, The Annals of pharmacotherapy.

[6]  M. Su,et al.  Mortality risk factors in patients with Acinetobacter baumannii ventilator: associated pneumonia. , 2011, Journal of the Formosan Medical Association = Taiwan yi zhi.

[7]  Ronald N. Jones,et al.  Contemporary activity of colistin and polymyxin B against a worldwide collection of Gram-negative pathogens: results from the SENTRY Antimicrobial Surveillance Program (2006-09). , 2011, The Journal of antimicrobial chemotherapy.

[8]  N. Goel,et al.  Trend analysis of antimicrobial consumption and development of resistance in non-fermenters in a tertiary care hospital in Delhi, India. , 2011, The Journal of antimicrobial chemotherapy.

[9]  K. Hızel,et al.  Nosocomial imipenem-resistant Acinetobacter baumannii infections: Epidemiology and risk factors , 2010, Scandinavian journal of infectious diseases.

[10]  D. Nicolau,et al.  Absence of Association between Use of Ertapenem and Change in Antipseudomonal Carbapenem Susceptibility Rates in 25 Hospitals , 2010, Infection Control & Hospital Epidemiology.

[11]  V. Tam,et al.  Surveillance and Correlation of Antibiotic Prescription and Resistance of Gram-Negative Bacteria in Singaporean Hospitals , 2010, Antimicrobial Agents and Chemotherapy.

[12]  V. Peraino,et al.  Introduction of Ertapenem into a Hospital Formulary: Effect on Antimicrobial Usage and Improved In Vitro Susceptibility of Pseudomonas aeruginosa , 2009, Antimicrobial Agents and Chemotherapy.

[13]  Michael Nikolaou,et al.  Pharmacodynamic Modeling of Aminoglycosides against Pseudomonas aeruginosa and Acinetobacter baumannii: Identifying Dosing Regimens To Suppress Resistance Development , 2008, Antimicrobial Agents and Chemotherapy.

[14]  Lisa L Maragakis,et al.  Acinetobacter baumannii: epidemiology, antimicrobial resistance, and treatment options. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  L. Hsu,et al.  IMP-4 and OXA β-lactamases in Acinetobacter baumannii from Singapore , 2007 .

[16]  K. Ko,et al.  Impact of imipenem resistance on mortality in patients with Acinetobacter bacteraemia. , 2007, The Journal of antimicrobial chemotherapy.

[17]  R. Polk,et al.  Measurement of adult antibacterial drug use in 130 US hospitals: comparison of defined daily dose and days of therapy. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[18]  J. Vila,et al.  Risk-factors for the acquisition of imipenem-resistant Acinetobacter baumannii in Spain: a nationwide study. , 2005, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[19]  Michael Nikolaou,et al.  Mathematical modelling of resistance emergence. , 2005, The Journal of antimicrobial chemotherapy.

[20]  Michael Nikolaou,et al.  Modelling time-kill studies to discern the pharmacodynamics of meropenem. , 2005, The Journal of antimicrobial chemotherapy.

[21]  Ronald N. Jones,et al.  Antimicrobial usage and resistance trend relationships from the MYSTIC Programme in North America (1999-2001). , 2004, The Journal of antimicrobial chemotherapy.

[22]  Tae Hyong Kim,et al.  Risk Factors for Acquisition of Imipenem-Resistant Acinetobacter baumannii: a Case-Control Study , 2004, Antimicrobial Agents and Chemotherapy.

[23]  K. Madaras-Kelly Optimizing Antibiotic Use in Hospitals: The Role of Population‐Based Antibiotic Surveillance in Limiting Antibiotic Resistance Insights from the Society of Infectious Diseases Pharmacists , 2003, Pharmacotherapy.

[24]  Gülseren Baran,et al.  Risk factors for nosocomial imipenem-resistant Acinetobacter baumannii infections. , 2008, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[25]  L. Hsu,et al.  IMP-4 and OXA beta-lactamases in Acinetobacter baumannii from Singapore. , 2007, The Journal of antimicrobial chemotherapy.

[26]  M. Ferraro Performance standards for antimicrobial susceptibility testing , 2001 .