{"id":621,"date":"2015-02-15T07:55:48","date_gmt":"2015-02-15T07:55:48","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=621"},"modified":"2017-01-04T11:27:31","modified_gmt":"2017-01-04T11:27:31","slug":"microbial-efficacy-analysis-of-potentox-a-fixed-dose-combination-of-cefepime-amikacin-with-cefepime-and-amikacin-alone-in-a-citrobacter-braaki-mycobacterium-smegmatis-acinetobacter-baumanii-and-nei","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol2no1\/microbial-efficacy-analysis-of-potentox-a-fixed-dose-combination-of-cefepime-amikacin-with-cefepime-and-amikacin-alone-in-a-citrobacter-braaki-mycobacterium-smegmatis-acinetobacter-baumanii-and-nei\/","title":{"rendered":"Microbial Efficacy Analysis of Potentox, a Fixed Dose Combination of Cefepime Amikacin with Cefepime and Amikacin Alone in a Citrobacter Braaki, Mycobacterium Smegmatis, Acinetobacter Baumanii and Neisseria mucosa"},"content":{"rendered":"

Introduction<\/strong><\/p>\n

Cefepime is a new broad spectrum parenteral fourth generation cephalosporin antibiotic with significant potential advantages over other broad\u00a0 spectrum cephalosporins and some nontraditional \u03b2 – lactam antibiotics.1, 2, 3<\/sup> In addition to a very broad antimicrobial spectrum, cefepime appears to have low affinity for major chromosomally mediated, \u03b2 – lactamases and those it less affected by the nonhydrolytic barrier mechanism of resistance in these bacteria.4<\/sup>\u00a0 <\/sup>Its high affinity for essential penicillin binding proteins, and its zwitterionic structure.5, 6<\/sup> Cefepime also appears to have a low propensity toward the development of resistance. Cefepime is generally active against gram negative bacteria resistance to other broad spectrum cephalosporins. Broad spectrum cephalosporins and aminoglycosides\u00a0 are highly active against aerobic gram negative bacteria. However, resistance to these agents has developed during their clinical use. These in vitro <\/em>advantages have been borne out in a number of in vivo\u00a0 <\/em>infection modal.7<\/sup> It is a active against\u00a0 a wider range of\u00a0 gram positive and gram\u00a0 negative aerobic organism.<\/p>\n

Combination therapy with an aminoglycoside plus an anti pseudomonal \u03b2 – lactam has commonly been recommended because this approach provides broad spectrum coverage, bactericidal activity and potential synergistic effects, and minimizes the development of resistance during treatment.8 <\/sup>Extended spectrum \u03b2 – lactamases (ESBL) production is one of the main mechanisms of resistance to \u03b2 – lactam antotics among the strains of family Enterobacteriaciaceae.9<\/sup> \u00a0The therapeutic choices in infections caused by such strains remain limited because of cross resistance.10<\/sup><\/p>\n

Conflicting <\/em>reports have been published concerning the activities of the\u00a0 broad – spectrum and fourth generation cephalosporins with an explanation of the inoculum effect.<\/em>11, 12, 13<\/sup><\/em> Cefepime and amikacin acts synergistically and has a broad spectrum <\/em>in vitro <\/em>activity that in enompasses a wide range of gram positive and gram negative bacteria. Cefepime has a low affinity\u00a0 for chromosomally encoded\u00a0 \u03b2 –\u00a0 lactamases.<\/em><\/p>\n

Amikacin is an aminoglycoside antibiotic used to treat different types of bacterial infections. amikacin works by binding to the bacteria 30 S ribosome subunit, causing misreading of\u00a0 m-RNA and leaving the bacterium unable to synthesize proteins vital to its growth. Amikacin is most often used for treating severe, hospital acquired infections with multi drug resistant gram negative bacteria such as \u00a0<\/strong>C. braaki, M. smegmatis, A. baumanii <\/em>and Neisseria mucosa.<\/em><\/p>\n

Amikacin is semi synthetic aminoglycoside antibiotic for the treatment of\u00a0 some gram negative and other infection. Amikacin belong to the aminoglycosides and is active against aerobic gram negative bacilli, including pseudomonas. It dose not have activity against anaerobes, and alone they are inactive against streptococci. Aminoglycosides are usually used in the treatment of serious infections with aerobic gram negative bacilli, including\u00a0 pseudomonas, complicated urinary tract infections.<\/p>\n

Materials and Methods<\/strong><\/p>\n

Bacterial Strains<\/strong><\/p>\n

Following strains obtained from Microbial Type Collection Center of Institute of Microbial Technology, Chandigarh, India were used for the study, Citrobacter braaki <\/em>(MTCC No. – 2690), Mycobacterium smegmatis<\/em> (MTCC No. – 995), Acinetobacter baumanii<\/em> (MTCC No. – 1425) and Neisseria mucosa<\/em> (MTCC No. – 1722).<\/p>\n

Antibiotic<\/strong><\/p>\n

Cefepime amikacin and potentox used in study were provided by manufacturer (Venus Remedies Limited, India) for the study.<\/p>\n

Medium<\/strong><\/p>\n

Mueller Hinton (MH) broth supplemented with calcium (25 mg\/l) and Magnesium (1.25 mg\/l) was used for susceptibility tests. Colony counts were determined with MH agar plates.<\/p>\n

Susceptibility\u00a0 Testing<\/strong><\/p>\n

The Minimum Inhibitory Concentration (MIC) of potentox, cefepime and amikacin alone, against C. braaki, M. smegmatis, A. baumanii <\/em>and N. mucosa <\/em>were determined by broth microdiluction method as per the standard National Committee for Clinical Laboratory Standards.14<\/sup> Overnight MH broth cultures were used to prepare inocula of 105 <\/sup>CFU\/ml. The MIC was defined as the lowest concentration of antimicrobial\u00a0 agent that prevented\u00a0 turbidity after 24 hours of\u00a0 incubation at 37 0<\/sup>C.<\/p>\n

Results<\/strong><\/p>\n

MIC studies<\/strong><\/p>\n

In case of C. braaki, M. smegmatis, A. baumanii<\/em> and N. mucosa<\/em> MIC were found to be in potentox 0.421mg\/l, 0.625mg\/l, 0.342mg\/l and 0.423 mg\/l. In cefepime alone the MIC\u00a0 were found to be 1.67mg\/l, 0.52mg\/l, 0.84mg\/l and 2.67 mg\/l respectively and\u00a0 in amikacin alone the MIC were found to be 3.34mg\/l, 1.67mg\/l, 2.67mg\/l and 1.0mg\/l. (Table -1)<\/p>\n

Table 1 : Results of\u00a0 Minimal Inhibitory Concentration Studies of <\/strong>\u00a0potentox, a fixed dose combination of cefepime amikacin with cefepime and amikacin alone.<\/strong><\/p>\n\n\n\n\n\n\n\n\n
\u00a0Mean Values of MIC (mg\/l)<\/strong><\/td>\n<\/tr>\n
S. No.<\/td>\nMicro-organisms<\/td>\nCefepime<\/td>\nAmikacin<\/td>\nPotentox<\/td>\n<\/tr>\n
1<\/td>\nC. braaki<\/em><\/td>\n1.67<\/td>\n3.34<\/td>\n0.421<\/td>\n<\/tr>\n
2<\/td>\nM. smegmatis<\/em><\/td>\n0.52<\/td>\n1.67<\/td>\n0.625<\/td>\n<\/tr>\n
3<\/td>\nA. baumanii <\/em><\/td>\n0.84<\/td>\n2.67<\/td>\n0.342<\/td>\n<\/tr>\n
4<\/td>\nN.<\/em> mucosa<\/em><\/td>\n2.67<\/td>\n1.00<\/td>\n0.423<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Susceptibility Studies<\/strong><\/p>\n

Antimicrobial Susceptibility Test of all microbial strains under study resulted in significant reduction in potentox\u00a0 when compared with cefepime and amikacin alone. (Table – 2)<\/p>\n

Table 2: Results of Antimicrobial Susceptibility Test studies of\u00a0 potentox, a fixed dose combination of cefepime amikacin with cefepime and amikacin alone.<\/strong><\/p>\n\n\n\n\n\n\n\n\n
S.No.<\/strong><\/td>\nMicroorganism<\/strong><\/td>\nZone diameter (mm)<\/strong><\/td>\n<\/tr>\n
Cefepime<\/strong><\/p>\n

Avg.\u00b1 S.D<\/strong><\/td>\n

Amikacin<\/strong><\/p>\n

Avg.\u00b1 S.D<\/strong><\/td>\n

Potentox<\/strong><\/p>\n

Avg.\u00b1 S.D<\/strong><\/td>\n<\/tr>\n

1<\/td>\nC. braaki<\/em><\/td>\n30.71\u00b10.7560<\/td>\n21.70\u00b10.5960<\/td>\n33.20\u00b10.5853<\/td>\n<\/tr>\n
2<\/td>\nM. smegmatis<\/em><\/td>\n23.50\u00b10.3760<\/td>\n22.63\u00b10.7350<\/td>\n29.11\u00b10.6230<\/td>\n<\/tr>\n
3<\/td>\nA. baumanii <\/em><\/td>\n30.70\u00b10.6330<\/td>\n17.65\u00b10.3870<\/td>\n32.80\u00b10.6280<\/td>\n<\/tr>\n
4<\/td>\nN.<\/em> mucosa<\/em><\/td>\n32.70\u00b10.5078<\/td>\n21.80\u00b10.36.52<\/td>\n34.15\u00b10.5162<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Note – <\/strong>Mean value \u00b1 Standered deviation value<\/p>\n

 <\/p>\n

In case of C. braaki, M. smegmatis, A. baumanii and N. mucosa AST were found of zone diameter to be 30.71mm, 23.50mm, 30.70mm and 32.70mm respectively of cefepime, for amikacin 21.70mm, 22.63mm, 17.65mm and 21.80mm respectively and for potentox 33.20mm, 29.11mm, 32.80mm and 34.15mm respectively.<\/p>\n

Discussion<\/strong><\/p>\n

The inappropriate use of antibiotics has contributed to the emergence of resistance globally with gram negative bacilli and gram positive bacteria.15<\/sup> The emerging mechanism of antibacterial resistance have compromised the effectiveness of the\u00a0 \u03b2 \u2013 lactam. Cefepime is a newly developed fourth generation\u00a0 cephalosporins with an extended spectrum of activity against many gram positive bacteria and gram negative organism, including multi resistance gram negative bacteria. Amikacin is particularly effective when used against bacteria that are resistant to other aminoglycosides, since its chemical structure makes it less\u00a0 susceptible to several inactivating enzymes. Antibiotic combinations including a \u03b2 – lactam and an aminoglycoside have frequently produced an increased bactericidal effect in in vivo<\/em> experimental models of aerobic gram negative bacillary infections which has generally paralleled an increased rate of\u00a0 killing in vitro.<\/em>16 <\/sup><\/p>\n

Combination therapy with an aminoglycoside plus an anti pseudomonal \u03b2 – lactam has commonly been recommended because this approach provides broad spectrum coverage, bactericidal activity and potential synergistic effects, and minimizes the development of resistance during treatment. To start with mono therapy\/combination\u00a0 broad spectrum empiric antibiotics are used, then switching to narrow\u00a0 spectrum specific therapy as guided by microbiological result. Appropriate \u03b2 \u2013 lactam antibiotics are recommended in international and German guidelines for the treatment of mono therapy and combination therapy.17<\/sup> In comparison with older cephalosporins, cefepime crosses the bacterial outer membrane faster. Cefepime has advantages of rapid penetration in periplasmic space and extended spectrum of activity that include gram positive and gram negative organisms.18<\/sup><\/p>\n

The therapeutic choices in infections caused by such strains remain limited\u00a0 because of cross resistance. Potentox\u00a0 acts synergistically\u00a0 and\u00a0 has a broad spectrum in vitro<\/em> activity\u00a0 that encompasses a wide range of gram positive and gram negative bacteria. Susceptibility data from our study demonstrated\u00a0 that\u00a0 potentox\u00a0 has lower MIC value than cefepime and amikacin alone, suggesting higher bactericidal activity in potentox. The in\u00a0 vitro<\/em> susceptibilities of ESBL\u00a0 producing strains to cefepime have been found to be 52 or 90%.19<\/sup> Cefepime was recommended for the treatment based on this in vitro<\/em> susceptibility.20<\/sup> Cefepime and amikacin acts synergistically and\u00a0 has a broad spectrum\u00a0 in vitro<\/em>\u00a0 activity\u00a0 that\u00a0 encompasses a wide range of gram positive\u00a0 and gram negative bacteria. Cefepime has a low affinity\u00a0 for\u00a0 chromosomally encoded \u03b2 – lactamases.<\/p>\n

In conclusion, the results by the statistical analysis of MIC and AST studies are in similar pattern for C. braaki, M. smegmatis, A. baumanii <\/em>and N. mucosa <\/em>Potentox has shown better bactericidal effect than cefepime and amikacin alone in organisms under study.<\/p>\n

Reference<\/strong><\/p>\n

    \n
  1. Clarke A.M., Zemcov S.J.V. and Wright J.M., HR \u2013 810 and BMY \u2013 28142 two new cephalosporins with broad spectrum activity : an in – vitro <\/em>comparison with other \u03b2 \u2013 lactam antibiotics, J. Antimicrob.\u00a0 Chemother., 15 : 305 \u2013 310 (1985).<\/li>\n
  2. Kessler R.E. et al<\/em>., Comparison of a new cephalosporin, BMY 28142, with other broad \u2013 spectrum \u03b2 \u2013 lactam\u00a0 antibiotics, Antimicrob. Agents Chemother., <\/em>27 : 207 \u2013 216 (1985).<\/li>\n
  3. Tsuji A., Maniatis A., Bertram M.A. and Young L.S., In \u2013 vitro <\/em>activity of BMY 28142 in comprision with those of other\u00a0 \u03b2 – lactam antimicrobial agents, Antimicrob. Agents Chemother., 27 : 515 \u2013 519 (1985).<\/li>\n
  4. Phelps D.J., Carlton D.D., Farrell C.A. and Kessler R.E., Affinity of cephalosporins for \u03b2 \u2013 lactamases\u00a0 as a factor in antibacterial efficacy, Antimicrob. Agents\u00a0 Chemother., 29 : 845 – 884 (1986).<\/li>\n
  5. Wynd M.A. and Paladino J.A., Cefepime : a fourth generation parenteral cephalosporin, Ann. Pharmacother., 30 : 1414 – 24 (1996).<\/li>\n
  6. Barradell L.B. and Bryson H.M., Cefepime A review of its antibacterial activity, pharmacokinetic properties and therapeutic use, Drugs., 47 : 471 – 505 (1994).<\/li>\n
  7. Tauber N.M.G., Hackbarth G.J., Scott K.G., Rusnak M.G. and Sande M.A., New cephalosporins cefotaxime, cefpimizole, BMY 28142, and HR 810 in experimental pneumococcal meningitis in rabbits, Antimicrob. Agents Chemother., 27 : 340 – 342 (1985).<\/li>\n
  8. Hughes W.T., Armstrong D., Bodey G.P., Brown A.E., Edwards J.E. and Feld R., Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Infectious Diseases Society of America, Clinical Infectious Diseases.,\u00a0 25 : 551 \u2013 73 (1997).<\/li>\n
  9. Jacoby G.A. and Medeiros A.A., Motrer extended spectrum \u03b2 \u2013 lactamases, Antimicrob. Agents Chemother., 35 : 1697 – 1704 (1991).<\/li>\n
  10. Brun – Buisson C., Legrand P., Philippon A., Montravers F., Ansquer M. and Duval J., Transferable enzymatic resistance to third generation cephalosporins during nosocomial outbreak of multiresistant Klebsiella pneumoniae, <\/em>Lancet., 2 : 302 \u2013 6 (1987).<\/li>\n
  11. Caron F.L. et al<\/em>., Ceftriaxone sulbactam combination in rabbit endocarditis caused by a strain of Klebsiella pneumoniae<\/em> producing extended\u00a0 broad spectrum TEM-3\u00a0 \u03b2 \u2013 lactamase, Antimicrob.\u00a0 Agents Chemother., 34 : 2070 – 2074 (1990).<\/li>\n
  12. Jett B.D., Ritchie D.J., Reichley R., Bailey T.C. and Sahm D.F.,\u00a0 In – vitro<\/em> activities of various \u03b2 – lactam antimicrobial agents against clinical isolates of Escherichia coli<\/em> and Klebsiella <\/em>spp<\/em>. resistant to oxyimino cephalosporins, Antimicrob. Agents Chemother., 39 : 1187 \u2013 1190 (1995).<\/li>\n
  13. Thauvin – Eliopoulos C., Tripodi M.F., Moellering Jr. and Eliopoulos G.M., <\/em>Efficacies of piperacillin-tazobactam and cefepime in rats with experimental intra abdominal abscesses due to an extended-spectrum \u03b2<\/em> \u2013<\/em> lactamase – producing strain of <\/em>Klebsiella pneumoniae<\/em>,<\/em> Antimicrob. Agents Chemother., <\/em>41<\/em> : <\/em>1053 – 1057 (1997).<\/em><\/li>\n
  14. National Committee for Clinical Laboratory Standards Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 4th ed. Approved standard M7 \u2013 A4, National Committee for Clinical Laboratory Standards., (1997).<\/li>\n
  15. Masterton R., Drusano G.L., Paterson D.L. and Park G., Appropriate antimicrobial treatment in nosocomial infection the clinical challenges, J. Hosp. Infect., 55 : 1-12 (2003).<\/li>\n
  16. Fantin B. and Carbon C.,\u00a0 In vivo<\/em> synergism : contribution of animal models, Antimicro. Agents and Chemotherapy., 36 : 907 – 12 (1992).<\/li>\n
  17. Bodmann K.F., Current guidelines for the treatment of severe pneumonia and sepsis, Chemotherapy., \u00a051 (5) : 227 – 3 (2005).<\/li>\n
  18. Angelescu M. and Apostol A., Cefepime (maxipime), large spectrum 4th generation cephalosporin, resistant to \u03b2 \u2013 lactamases, Chirurgia., 96 (6) : 547 – 52 (2001).<\/li>\n
  19. Silva J. et al.,<\/em> Susceptibility to new \u03b2 – lactams of enterobacterial extended spectrum \u03b2 – lactamase (ESBL) producers and penicillin resistant Streptococcus pneumoniae <\/em>in Mexico., J. Chemother., 10 :102 -107 (1998).<\/li>\n
  20. Gould I.M., Do we need fourth generation cephalosporins? Clin. Microbiol. Infect., 5 : S1 \u2013S5 (1999).<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

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