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BRIEF COMMUNICATION
Year : 2016  |  Volume : 34  |  Issue : 4  |  Page : 513-515
 

Can minocycline be a carbapenem sparing antibiotic? Current evidence


Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India

Date of Submission29-Sep-2016
Date of Acceptance12-Oct-2016
Date of Web Publication8-Dec-2016

Correspondence Address:
B Veeraraghavan
Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0255-0857.195380

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 ~ Abstract 

With the increasing incidence of multidrug-resistant organisms, there is a need for newer antibiotics. However, due to the lack of new antimicrobial agents, it is necessary to re-evaluate the older agents like minocycline which is a second-line antimicrobial agent. In this study, minocycline susceptibility testing was performed for 693 Escherichia coli, 316 Klebsiella spp. and 89 Acinetobacter spp. Among extended spectrum beta-lactamase producing E. coli and Klebsiella spp. percentage susceptibility to minocycline were 76 and 85, respectively. Among the carbapenem resistant E. coli, Klebsiella spp. and Acinetobacter spp. minocycline susceptibility were 52%, 55% and 42%, respectively. Based on the susceptibility profile, minocycline can be considered for treatment of infections by multidrug-resistant organisms.


Keywords: Acinetobacter spp., Escherichia coli, Klebsiella spp., minocycline


How to cite this article:
Veeraraghavan B, Shankar C, Vijayakumar S. Can minocycline be a carbapenem sparing antibiotic? Current evidence. Indian J Med Microbiol 2016;34:513-5

How to cite this URL:
Veeraraghavan B, Shankar C, Vijayakumar S. Can minocycline be a carbapenem sparing antibiotic? Current evidence. Indian J Med Microbiol [serial online] 2016 [cited 2017 Feb 26];34:513-5. Available from: http://www.ijmm.org/text.asp?2016/34/4/513/195380



 ~ Introduction Top


Minocycline is a second-generation tetracycline with improved pharmacological properties than tetracycline. It has longer half-life, better oral absorption, superior tissue penetration, change from intravenous to oral therapy, limited toxicity and most importantly can evade tetracycline-resistance mechanisms.[1]

Tigecycline is the first member of glycylcycline which is derived from minocycline by the addition of a 9-tert-butyl-glycylamido side chain to the D ring at the ninth position of minocycline. This side chain aids in overcoming the ribosomal protection proteins and efflux pumps which confer resistance to other tetracyclines.[2],[3] Both the antibiotics act by inhibiting protein synthesis.

Carbapenem-resistant (CR) organisms are on the rise globally which leaves tigecycline and colistin as a last resort for treatment. With increased usage, resistance to tigecycline has increased, within a few years, tigecycline might be rendered obsolete. It is worthwhile to reconsider the efficacy and use of some of the older antibiotics such as minocycline for the treatment of multidrug-resistant organisms.


 ~ Materials and Methods Top


From August 2015 to July 2016, 693 Escherichia coli, 316 Klebsiella spp. and 89 Acinetobacter spp. isolated from patients with bacteraemia at the Department of Clinical Microbiology, Christian Medical College (CMC), Vellore was subjected to susceptibility testing to minocycline and tigecycline along with the first- and second-line antibiotics by disc diffusion method. For Acinetobacter spp., only the CR isolates were included in the study. The results were interpreted according to the Clinical and Laboratory Standards Institute guidelines for all antibiotics. For tigecycline, breakpoints are described only by FDA for Enterobacteriaceae but Acinetobacter there are no breakpoints available. Percentage susceptibility of extended spectrum beta-lactamase (ESBL) producing and CR Enterobacteriaceae and Acinetobacter spp. to minocycline were calculated.


 ~ Results and Discussion Top


[Table 1] summarises the results of susceptibility testing by disc diffusion to meropenem, minocycline and tigecycline among the multidrug-resistant isolates from CMC hospital. Multidrug-resistant isolates are defined as those that are resistant to at least one agent in three or more classes of antimicrobials. Among ESBL producing E. coli and Klebsiella spp. percentage susceptibility to minocycline were 76 and 85, respectively. Among the CR E. coli, Klebsiella spp. and Acinetobacter spp. minocycline susceptibility were 52%, 55% and 42%, respectively. Only CR Acinetobacter spp. was included in the study and the susceptibility to minocycline is lesser than that of CR Enterobacteriaceae isolates.
Table 1: Results of in-vitro susceptibility testing by disc diffusion from CMC between August 2015 to July 2016, Vellore

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Nine and six clinical isolates each of K. pneumoniae and A. baumannii were found to be susceptible to minocycline but resistant to tigecycline. Similar results have been reported by Goff and Kaye.[4] Ritchie and Garavaglia-Wilson, propose the inclusion of minocycline in the panel of antimicrobials to be tested especially for A. baumannii and not to use tetracycline as a surrogate marker.[5] Unlike tetracycline resistance which occurs mainly through increased efflux activity and ribosomal protection proteins, minocycline resistance in A. baumannii has been reported to be associated with the tet (B) efflux gene along with the plasmid-mediated ISCR-2 mobile element. Therefore, to avoid discrepant results, minocycline testing should be considered.

The literature regarding the combination testing with minocycline is limited. In 2007, Tan et al., showed 92% and 69% synergistic and bactericidal effect respectively by time-kill assay (TKA) when 13 imipenem-resistant A. baumannii were tested against a combination of minocycline with colistin.[6] Liang et al. in 2011, reported 100% synergistic activity for both minocycline with colistin and minocycline with meropenem against four extremely drug-resistant A. baumannii by TKA.[7] In 2012, Pei et al. investigated 53 CR A. baumannii against cefoperazone/sulbactam by checkerboard assay (CB) and showed 73.5% synergistic activity.[8] Recently, Zhang et al. tested 25 pan-drug resistant A. baumannii by CB showed 44% synergism for minocycline with polymyxin B.[9] There are no similar studies for Enterobacteriaceae reported.

In the recent years, there has been growing interest in minocycline for the treatment of multidrug-resistant Gram-negatives. [Table 2] details the percentage susceptibility of E. coli, K. pneumoniae and Acinteobacter spp. for meropenem, minocycline and tigecycline as determined by microbroth dilution by Tigecycline Evaluation and Surveillance Trial (TEST) studies. The TEST study conducted globally reports the minimum inhibitory concentrations (MICs) for minocycline, tigecycline and meropenem. Hoban et al. report highest susceptibility of A. baumannii to minocycline (84.5%) among all the other antibiotics tested. It is evident from [Table 2] that an average of 59% ESBL E. coli and 51% of ESBL K. pneumoniae can be treated with minocycline. However, a higher rate of susceptibility is seen among ESBL producers in this study as mentioned in [Table 1]. Approximately, 50% of the CR E. coli and K. pneumoniae can be treated with minocycline based on previous TEST studies detailed in [Table 2]. Similar results were obtained for minocycline susceptibility by disc diffusion from CMC for CR E. coli and K. pneumoniae [Table 1].
Table 2: Percentage susceptibility of E. coli, K.pneumoniae and A.baumannii for meropenem, minocycline and tigecycline as determined by microbroth dilution by TEST studies

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MIC has to be determined to consider minocycline as an alternative choice based on susceptibility profile. In addition, the lower MIC of other antibiotic can be a combination choice.

Till date, in vivo studies reported on the efficacy of minocycline for both monotherapy and combination therapy includes the following. Wood et al. and Griffith et al. in their studies using minocycline as monotherapy against wound infection and ventilator-associated pneumonia due to A. baumannii have reported 88% and 100% clinical cure, respectively.[13],[14] In in vivo studies, using minocycline both as monotherapy as well as in combination with other antimicrobial agents, Chan et al. reported 81% clinical cure for pneumonia due to A. baumannii[15] and Pogue et al. reported 69% clinical cure for bloodstream infection and pneumonia due to A. baumannii and CR K. pneumoniae.[16]

Although these in vivo studies include small number of patients, they show that minocycline can be used in treatment based on susceptibility. Hence, large multicentric studies are necessary to prove the safety and efficacy of minocycline for treating multidrug-resistant infections.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 ~ References Top

1.
Shankar C, Nabarro LE, Anandan S, Veeraraghavan B. Minocycline and Tigecycline: What Is Their Role in the Treatment of Carbapenem-Resistant Gram–Negative Organisms?. Microbial Drug Resistance. 2016. PubMed: 27564414. DOI: 10.1089/mdr.2016.0043.  Back to cited text no. 1
    
2.
Chopra I, Roberts M. Tetracycline antibiotics: Mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev 2001;65:232-60.  Back to cited text no. 2
    
3.
Schafer JJ, Goff DA. Establishing the role of tigecycline in an era of antimicrobial resistance. Expert Rev Anti Infect Ther 2008;6:557-67.  Back to cited text no. 3
    
4.
Goff DA, Kaye KS. Minocycline: An old drug for a new bug: Multidrug-resistant Acinetobacter baumannii. Clin Infect Dis 2014;59 Suppl 6:S365-6.  Back to cited text no. 4
    
5.
Ritchie DJ, Garavaglia-Wilson A. A review of intravenous minocycline for treatment of multidrug-resistant Acinetobacter infections. Clin Infect Dis 2014;59 Suppl 6:S374-80.  Back to cited text no. 5
    
6.
Tan TY, Ng LS, Tan E, Huang G.In vitro effect of minocycline and colistin combinations on imipenem-resistant Acinetobacter baumannii clinical isolates. J Antimicrob Chemother 2007;60:421-3.  Back to cited text no. 6
    
7.
Liang W, Liu XF, Huang J, Zhu DM, Li J, Zhang J. Activities of colistin-and minocycline-based combinations against extensive drug resistant Acinetobacter baumannii isolates from intensive care unit patients. BMC Infect Dis 2011;11:1.  Back to cited text no. 7
    
8.
Pei G, Mao Y, Sun Y.In vitro activity of minocycline alone and in combination with cefoperazone-sulbactam against carbapenem-resistant Acinetobacter baumannii. Microb Drug Resist 2012;18:574-7.  Back to cited text no. 8
    
9.
Zhang Y, Chen F, Sun E, Ma R, Qu C, Ma L.In vitro antibacterial activity of combinations of fosfomycin, minocycline and polymyxin B on pan-drug-resistant Acinetobacter baumannii. Exp Ther Med 2013;5:1737-9.  Back to cited text no. 9
    
10.
Hoban DJ, Reinert RR, Bouchillon SK, Dowzicky MJ. Global in vitro activity of tigecycline and comparator agents: Tigecycline evaluation and surveillance trial 2004-2013. Ann Clin Microbiol Antimicrob 2015;14:27.  Back to cited text no. 10
    
11.
Fernández-Canigia L, Dowzicky MJ. Susceptibility of important Gram-negative pathogens to tigecycline and other antibiotics in Latin America between 2004 and 2010. Ann Clin Microbiol Antimicrob 2012;11:1.  Back to cited text no. 11
    
12.
Denys GA, Callister SM, Dowzicky MJ. Antimicrobial susceptibility among gram-negative isolates collected in the USA between 2005 and 2011 as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.). Ann Clin Microbiol Antimicrob 2013;12:24.  Back to cited text no. 12
    
13.
Wood GC, Hanes SD, Boucher BA, Croce MA, Fabian TC. Tetracyclines for treating multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia. Intensive Care Med 2003;29:2072-6.  Back to cited text no. 13
    
14.
Griffith ME, Yun HC, Horvath LL, Murray CK. Minocycline therapy for traumatic wound infections caused by the multidrug-resistant Acinetobacter baumannii-Acinetobacter calcoaceticus Complex. Infect Dis Clin Pract 2008;16:16-9.  Back to cited text no. 14
    
15.
Chan JD, Graves JA, Dellit TH. Antimicrobial treatment and clinical outcomes of carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia. J Intensive Care Med 2010;25:343-8.  Back to cited text no. 15
    
16.
Pogue JM, Neelakanta A, Mynatt RP, Sharma S, Lephart P, Kaye KS. Carbapenem-resistance in gram-negative bacilli and intravenous minocycline: An antimicrobial stewardship approach at the Detroit Medical Center. Clin Infect Dis 2014;59 Suppl 6:S388-93.  Back to cited text no. 16
    



 
 
    Tables

  [Table 1], [Table 2]



 

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