title: In Vitro Fractional Inhibitory Concentration (FIC) Study of Cefixime and Azithromycin Fixed Dose Combination (FDC) Against Respiratory Clinical Isolates.
abstract: BACKGROUND
  Acute respiratory infections (ARI) contribute to more than 75% of health care seeking in primary health care facilities in India. Respiratory tract infections (RTIs) are managed frequently by β-lactam, macrolide and fluroquinolone class of antibiotics. However, these recommended classes of antibiotic have shown resistance in community settings. Antibiotic combinations may provide broader spectrum not only in terms of coverage but also to overcome multiple resistance mechanisms overcoming individual class limitations.
  
  
  OBJECTIVE
  The study aimed to determine In vitro interactions interpreted according to calculated fractional inhibitory concentration (FIC) index between cefixime and azithromycin against common respiratory clinical isolates.
  
  
  METHODS
  Forty four bacterial respiratory clinical isolates from microbiology department of tertiary care hospital from Mumbai were used to determine the minimum inhibitory concentration (MIC) values of cefixime and azithromycin. Synergy testing of cefixime combination with azithromycin was performed by checkerboard method. Interaction was determined according to calculated FIC index.
  
  
  RESULTS
  MIC values were ranging from 2-128 μg/ml and 0.24-128 μg/ml for cefixime and azithromycin respectively against K.pneumoniae, M.catarrhalis, S.pneumoniae and H.influenzae isolates. All the tested isolates were resistant to cefixime. Azithromycin resistance was noted in all the isolates except six M. catarrhalis isolates. FIC index showed synergy and additive effect in 66% (29/44) and 34% (15/44) all bacterial clinical isolates. Maximum synergy between cefixime and azithromycin was observed against K. pneumoniae in 91% isolates.
  
  
  CONCLUSIONS
  This is one of the first attempts to check the rationality of fixed dose antibiotic combination of cefixime and azithromycin in India market. Though results of this study cannot be generalized considering the limitations of low sample size and in vitro model, our data provides stepping stone for further validation of cefixime and azithromycin fixed dose combinations (FDCs) in clinical setting by conducting randomized controlled trials. We think that judicious and rational use of FDCs may help to reduce the risk of selection of further drug resistance along with better clinical outcome.
authors: Assistant Manager, Medical Services, Glenmark Pharmaceuticals Ltd , Andheri(E). Mumbai, India .
authors: Saiprasad Vilas
authors: SV
authors: Patil
authors: Assistant Manager, Medical Services, Glenmark Pharmaceuticals Ltd , Andheri(E). Mumbai, India .
authors: Anoop Laxminarayan
authors: AL
authors: Hajare
authors: Lecturer, Department of Pharmacology, D.Y. Patil Medical College , Navi Mumbai, India .
authors: Manjusha
authors: M
authors: Patankar
authors: Deputy General Manager, Medical Services, Glenmark Pharmaceuticals Ltd , Andheri(E). Mumbai, India .
authors: K
authors: K
authors: Krishnaprasad
keywords: Acute respiratory infections; Fixed dose combination; Fractional inhibitory concentration index; Minimum inhibitory concentration; Synergy