Potential role of the cardiovascular non-antibiotic (helper compound) amlodipine in the treatment of microbial infections: scope and hope for the future

Mazumdar, Kaushiki; Kumar, K. Asok; Dutta, Noton K.

doi:10.1016/j.ijantimicag.2010.05.003

Cited by 34 publications

(31 citation statements)

References 54 publications

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“…Recently, an effective approach has been to explore non-antibiotic compounds (helper compounds) that express antibacterial properties, possibly by acting through different mechanisms from those of existing drugs, either by the enhancement of antibiotic activity (synergism) or the reversal of antibiotic resistance, yielding sensitivity comparable to that derived from classical antibiotics in previously drug-resistant microorganisms [7]. Among these non-antibiotics, amlodipine (AML) is the most promising helper compound.…”

Section: Introductionmentioning

confidence: 99%

Effects of a combination of amlodipine and imipenem on 42 clinical isolates of Acinetobacter baumannii obtained from a teaching hospital in Guangzhou, China

Pan

Zhao

et al. 2013

BMC Infect Dis

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BackgroundThe clonal spread of Acinetobacter baumannii is a global problem, and carbapenems, such as imipenem, remain the first-choice agent against A. baumannii. Using synergy to enhance the antibiotic activity of carbapenems could be useful. Here, amlodipine (AML) was tested alone and with imipenem against A. baumannii isolates.MethodsForty-two isolates of A. baumannii were collected. Multilocus sequence typing (MLST) assessed the genetic relationship of the isolates. The resistance phenotypes were determined using disc diffusion. The minimum inhibitory concentrations (MICs) of the drugs were determined by broth microdilution. The combined effects of the drugs were determined by a checkerboard procedure. Metallo-β-lactamase (MBL) was determined using the MBL Etest.ResultsForty-two A. baumannii isolates were collected from 42 patients who were mostly older than 65 years and had long inpatient stays (≥7 days). A. baumannii was mostly recovered from the respiratory system (N = 35, 83.3%). Most patients (N = 27, 64.3%) received care in intensive care units (ICUs). Disc diffusion testing demonstrated that A. baumannii susceptibility to polymyxin B was 100%, while susceptibility to other antimicrobial agents was less than 30%, classifying the isolates into 10 MDR and 32 XDR strains. MLST grouped the A. baumannii isolates into 4 existing STs and 6 new STs. STn4 carried allele G1, with a T → C mutation at nt3 on the gpi111 locus. STn5 carried allele A1, possessing A → C mutations at nt156 and nt159 on the gltA1 locus. ST195 and ST208 accounted for 68.05% (29/42) of the isolates. Clonal relation analysis showed that ST195 and ST208 belonged to clonal complex (CC) 92. The inhibitory concentration of imipenem ranged from 0.5 to 32 μg/ml, and that of AML ranged from 40 to 320 μg/ml. In combination, the susceptibility rate of A. baumannii isolates increased from 16.7% to 54.8% (P = 0.001). In the checkerboard procedure, half of the isolates (N = 21, 50.0%) demonstrated synergy or partial synergy with the drug combination. The MBL Etest revealed that 1 A. baumannii strain (N = 1, 2.4%) produced MBL.ConclusionsCC92 was the major clone spreading in our hospital. AML improved the activity of imipenem against A. baumannii isolates in vitro but did not inhibit MBL.

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Section: Introductionmentioning

confidence: 99%

Effects of a combination of amlodipine and imipenem on 42 clinical isolates of Acinetobacter baumannii obtained from a teaching hospital in Guangzhou, China

Pan

Zhao

et al. 2013

BMC Infect Dis

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“…13 High doses of verapamil have been shown to inhibit the growth of Chlamydia, 14 and most interestingly, Ca 2+ channel blockers have been shown to improve antibiotic susceptibility of persistent C. pneumoniae infection, presumably by reactivating the persistent infection to more easily treatable acute infection. 15,16 We have previously shown that phenolic compounds, common in our daily food, are potent and valid inhibitors of C. pneumoniae, in vitro and in vivo, even with doses achievable from the nutritional sources.…”

Section: Introductionmentioning

confidence: 99%

Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro

et al. 2011

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Besides small molecules from medicinal chemistry, natural products are still major sources of innovative therapeutic agents for various conditions, including infectious diseases. Here we present the first attempt to design a combination treatment targeted against Chlamydia pneumoniae infection using coadministration of natural phenolics with calcium (Ca 2+ ) modulators, and also the concomitant administration of these compounds with doxycycline. An in vitro acute C. pneumoniae model in human lung epithelial cells was used and Loewe additivity model was applied to evaluate the effects. In general, the phenolic compounds, quercetin, luteolin, rhamnetin and octyl gallate did not improve the antichlamydial effect of doxycycline, and, in some cases, resulted in antagonistic effects. The combination of doxycycline and Ca 2+ modulators (isradipine, verapamil and thapsigargin) was at most additive, and at subinhibitory concentrations of doxycycline, often even antagonistic. The Ca 2+ modulators showed no inhibitory effects on C. pneumoniae growth alone, whereas the coadminstration of Ca 2+ modulators with phenolic compounds resulted in potentiation of the antichlamydial effect of phenolic compounds. Verapamil (100 lM) was synergistic with low quercetin and luteolin concentrations (0.39 and 1.56 lM), whereas 10 lM isradipine was synergistic with high quercetin, rhamnetin and octyl gallate concentrations (12.5 lM and 100 lM). Use of thapsigargin with the phenolic compounds resulted in the most intense synergism. Interaction indices 0.12 and 0.14 were achieved with 0.39 lM luteolin and 10 and 100 nM thapsigargin, respectively. To conclude, the observed results indicate that the Ca 2+ modulators potentiate the antichlamydial effects of the phenolic compounds.

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“…Unexpectedly, studies by Paul Ehrlich showed that the vital dye methylene blue could be efficacious in the treatment of malaria and the dye trypan red is active against trypanosomiasis in horses and the dye salvarsan had an antisyphilitic action. 1,9 After the discovery of penicillin by Alexander Fleming, the antimicrobial chemotherapeutic agents usage minimized within a short period of time. A very large number of antibiotic compounds flooded in the medical world and most of these provided quick remedy against gram (+) ve and gram (-) [10][11] After many years, the unsystematic usage of antibiotics for prolonged periods had its limitations as microorganisms gradually began to rise in the form of antibiotic resistant microbes.…”

Section: The Antibiotic and Non-antibiotic Storymentioning

confidence: 99%

“…While cyproheptadine is an anti-histamine and is also an anabolic stimulant. 1 It is reported that post cataract inflammation could be managed with diclofenac-gentamycin eye drops which was proved to be more effective than gentamycin eye drops. 24 Ascorbic acid also enhances the antibacterial activity with aminopenicillinampicillin.…”

Section: The Antibiotic and Non-antibiotic Storymentioning

confidence: 99%

“…This problem has been manifested by using the different combinational therapy or new antimicrobial agents to treat drug resistant infections. 1 In this context, it has become essential to identify effective antimicrobial agents. A different variety of compounds which are employed in the management of pathological conditions of non-infectious diseases have also been shown to alter cell permeability and to exhibit wide range of activity in vitro against specific microorganism.…”

Section: Introductionmentioning

confidence: 99%

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Studies on Anti microbial Potential of Non-antibiotics on Resistant Bacteria – A Review

Krishnan¹,

Kandasamy²

2015

JYP

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The non-chemotherapeutic compounds, synthetic compounds and naturally isolated compounds possess good antimicrobial activity against microbial infections is a well-known fact. In this state the term non-antibiotics is taken to include a variety of pharmacologically active compounds which are useful in the management of pathological conditions of anon-infectious diseases that modify cell permeability and have been shown to exhibit broad spectrum antimicrobial activity. Of the nonantibiotic medicinal compounds, neuroleptic as well as phenothiazine inhibited the extracellular and intracellular efflux pump system and particularly intracellular efflux pumps has been the main research focus in multidrug resistant gram positive and gram negative microorganisms. The increase and spread of drug resistance is exerted by unsystematic usage of antibiotics for prolonged periods and over use of antimicrobials. Antimicrobial agents are inactivated by the following resistance mechanisms. Multi drug efflux pump and alteration of membrane protein are based on the persistence of resistance genes. A review of literature on a number of research articles suggests that some of these and other membrane active compounds improve the activity of conventional antibiotics, eliminate the natural resistance to particular antibiotics, and exhibit good activity against multi drug resistant form of Mycobacterium tuberculosis and methicillin resistant staphylococcus aureus. Thus, non-antibiotics particularly anti depressants, antipsychotics, anti-hypertensive agent, anti-spasmodic drug, anti-inflammatory agent and Cardio vascular drug have a significant role in the treatment of microbial infections which had shown their synergistic effect with penicillin and some other antibiotics. These effects would help to reduce the dose of antibiotics to patients suffering from specific bacterial infections.

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Potential role of the cardiovascular non-antibiotic (helper compound) amlodipine in the treatment of microbial infections: scope and hope for the future

Cited by 34 publications

References 54 publications

Effects of a combination of amlodipine and imipenem on 42 clinical isolates of Acinetobacter baumannii obtained from a teaching hospital in Guangzhou, China

Effects of a combination of amlodipine and imipenem on 42 clinical isolates of Acinetobacter baumannii obtained from a teaching hospital in Guangzhou, China

Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro

Studies on Anti microbial Potential of Non-antibiotics on Resistant Bacteria – A Review

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