title: Synergy of drug combinations in treating multidrug-resistant Pseudomonas aeruginosa.
abstract: BACKGROUND
  With the emergence of metallo-betalactamases (MBL) in Pseudomonas aeruginosa (P. aeruginosa), the value of carbapenem, the drug of last resort, is being severely compromised. Curtailing the use of carbapenems becomes paramount if resistance is to be reined in.
  
  
  OBJECTIVE
  To study the role of synergy between combinations of drugs as an alternative treatment choice for P. aeruginosa. Synergy was studied between combinations of levofloxacin with piperacillin-tazobactam and levofloxacin with cefoperazone-sulbactam by time-kill and chequerboard techniques.
  
  
  METHODS
  P. aeruginosa were tested for antibiotic susceptibility by the disc diffusion assay (260 isolates) and E-test (60 isolates). Synergy testing by chequerboard and time-kill assays was performed with combinations of piperacillin-tazobactam with levofloxacin (11 isolates) and cefoperazone-sulbactam with levofloxacin (10 isolates).
  
  
  RESULTS
  Nearly all isolates were susceptible to piperacillin-tazobactam (96.1 per cent), followed by piperacillin (78.5 per cent). Seventy-one isolates (27.3 per cent) were found to be multidrug resistant and 19.6 per cent were ESBL producers. MIC50 of amikacin was 32μg/ml and MIC90 was 64μg/ml. MIC50 and MIC90 of cefoperazone-sulbactam was 32μg/ml and 64μg/ml, and for levofloxacin it was 10μg/ml and 240μg/ml, respectively. Piperacillin-tazobactam had MIC50 and MIC90 of 5μg/ml and 10μg/ml, respectively. Synergy was noted in 72.7 per cent isolates for levofloxacin and piperacillin-tazobactam combination, the remaining 27.3 per cent isolates showed addition by both chequerboard and time-kill assay. For levofloxacin and cefoperazone-sulbactam, only 30 per cent isolates had synergy, 40 per cent showed addition, 20 per cent indifference, and 10 per cent were antagonistic by the chequerboard method.
  
  
  CONCLUSIONS
  The combination of levofloxacin and piperacillin-tazobactam is a good choice for treatment of such strains.
authors.affiliation: Dept. of Microbiology, Jawaharlal Nehru Medical College & Hospital, Amu, India.
authors.forename: Meher
authors.initials: M
authors.lastname: Rizvi
authors.affiliation: Dept. of Microbiology, Jawaharlal Nehru Medical College & Hospital, Amu, India.
authors.forename: Junaid
authors.initials: J
authors.lastname: Ahmad
authors.affiliation: Dept. of Microbiology, Jawaharlal Nehru Medical College & Hospital, Amu, India.
authors.forename: Fatima
authors.initials: F
authors.lastname: Khan
authors.affiliation: Dept. of Microbiology, Jawaharlal Nehru Medical College & Hospital, Amu, India.
authors.forename: Indu
authors.initials: I
authors.lastname: Shukla
authors.affiliation: Dept. of Microbiology, Jawaharlal Nehru Medical College & Hospital, Amu, India.
authors.forename: Abida
authors.initials: A
authors.lastname: Malik
authors.affiliation: Dept. of Microbiology, Jawaharlal Nehru Medical College & Hospital, Amu, India.
authors.forename: Hiba
authors.initials: H
authors.lastname: Sami
keywords: Multidrug resistance; chequerboard technique; synergy; time-kill assay
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