• Korean Journal of Clinical Laboratory Science
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• v.38 no.3
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• pp.166-172
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• 2006

Metallo-${\beta}$-lactamase (MBL) can hydrolyze all ${\beta}$-lactams except monobactams and frequently coexists with various antibiotic resistance genes such as aminoglycoside resistance, sulfonamide resistance gene, etc. Therefore, the effective antibiotics against infections by these bacteria are markedly limited or can't even be found. We tried to search in-vitro antimicrobial combinations with synergistic effects for a VIM-2 type MBL producing Pseudomonas aeruginosa, isolated from clinical specimen. On the selection of antibiotic combinations with synergistic effects, we performed a one disk synergy test, modified Pestel's method, in agar without aztreonam (AZT). The bacteriostatic synergistic effects of this tests were scored as $S_1$ (by susceptibility pattern in agar without antibiotics), $S_2$ (by the change of susceptibility in agar with or without antibiotics) and $S_3$ ($S_1$ + $S_2$) and was classified into weak (1 point), moderate (2 points) and strong (3 points) by $S_3$ score. Subsequently, we carried out the time-killing curve for the antibiotic combinations with the strong synergistic bacteriostatic effect. One VIM-2 type MBL producing P. aeruginosa confirmed by the PCR showed all resistance against all ${\beta}$-lactams except AZT, aminoglycoside and ciprofloxacin. In the one disk synergy test, this isolate showed a strong bacteriostatic synergistic effect for the antibiotic combination of AZT and piperacillin-tazobactam (PIP-TZP) or AZT and amikacin (AN). On the time-killing curve after six hours of incubation, the colony forming units (CFUs/mL) of this bacteria in the medium broth with both combination antibiotics were decreased to 1/18.7, 1/17.1 of the least CFUs of each single antibiotics. The triple antibiotic combination therapy including AZT, PIP-TZP and AN was shown to be significantly synergistic after 8 hrs of exposure. In a VIM-2 MBL producing P. aeruginosa with susceptibility for AZT, the triple antibiotic combination therapy including AZT, PIP-TZP and AN may be considered as an alternative antibiotics modality against the infection by some MBL type. But the antimicrobial combination therapy for many more MBL producing isolates is essential to know as soon as possible for the selection of effective treatment against the infection by this bacteria.

• Journal of Pharmacopuncture
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• v.25 no.2
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• pp.79-87
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• 2022

Since ancient times, plants have been a major source of novel drug molecules and have been used in the treatment of different infectious diseases. Secondary plant metabolites have miraculous healing properties and show potent therapeutic responses when used in combination drug therapy. The prime objective of this review is to summarize the concept of drug combination with special emphasis on the synergistic interactions between plant-derived bioactive phytochemicals with commercially available antimicrobial agents. The study also assesses the roles, importance, and applicability of phytochemicals in the management of different diseases. The review focuses on different aspects of combined antimicrobial activities, the possible mechanisms involved, and the current status of research in the field. The study was conducted based on an extensive literature survey that resulted in the following hypothesis: secondary metabolites derived from plants possess remarkable therapeutic activities. The study was designed as a systematic review that ensures unbiased and accurate representations of the relevant data and information. Jadad scale selection criteria were used for qualitative analysis of the articles to assess them based on the relevant secure score (minimum and maximum scores range between 1 and 5, respectively). Articles with secure scores > 3 were considered for the study. A comprehensive literature survey was conducted using resource databases including PubMed, Google Scholar, Bielefeld Academic Search Engine, Research Gate, Scopus, Medline, and Science Direct up to June 2019. This article contains concise information about the most commonly used bioactive phytochemicals with potent antifungal and antibacterial effects.

• Journal of Microbiology and Biotechnology
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• v.28 no.11
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• pp.1771-1781
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• 2018

The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases that further threaten health, especially in immunodeficient populations, is a major global problem. The development of new antifungal agents in clinical trials is inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms aim at certain characteristics of the fungus in order to avoid biological similarities with the host. Synthesis of the cell wall and ergosterol are mainly targeted in clinical use. The need for new approaches to antifungal therapeutic agents or development alternatives has increased. This review explores new perspectives on mechanisms to effectively combat fungal infections and effective antifungal activity. The clinical drug have a common feature that ultimately causes caspase-dependent cell death. The drugs-induced cell death pathway is associated with mitochondrial dysfunction, including mitochondrial membrane depolarization and cytochrome c release. This mechanism of action also reveals antimicrobial peptides, the primary effector molecules of innate systems, to highlight new alternatives. Furthermore, drug combination therapy is suggested as another strategy to combat fungal infection. The proposal for a new approach to antifungal agents is not only important from a basic scientific point of view, but will also assist in the selection of molecules for combination therapy.

• Journal of Microbiology and Biotechnology
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• v.33 no.9
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• pp.1179-1188
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• 2023

Escherichia coli, particularly multidrug-resistant (MDR) strains, is a serious cause of healthcare-associated infections. Development of novel antimicrobial agents or restoration of drug efficiency is required to treat MDR bacteria, and the use of natural products to solve this problem is promising. We investigated the antimicrobial activity of dried green coffee (DGC) beans, coffee pulp (CP), and arabica leaf (AL) crude extracts against 28 isolated MDR E. coli strains and restoration of ampicillin (AMP) efficiency with a combination test. DGC, CP, and AL extracts were effective against all 28 strains, with a minimum inhibitory concentration (MIC) of 12.5-50 mg/ml and minimum bactericidal concentration of 25-100 mg/ml. The CP-AMP combination was more effective than CP or AMP alone, with a fractional inhibitory concentration index value of 0.01. In the combination, the MIC of CP was 0.2 mg/ml (compared to 25 mg/ml of CP alone) and that of AMP was 0.1 mg/ml (compared to 50 mg/ml of AMP alone), or a 125-fold and 500-fold reduction, respectively, against 13-drug resistant MDR E. coli strains. Time-kill kinetics showed that the bactericidal effect of the CP-AMP combination occurred within 3 h through disruption of membrane permeability and biofilm eradication, as verified by scanning electron microscopy. This is the first report indicating that CP-AMP combination therapy could be employed to treat MDR E. coli by repurposing AMP.

• Archives of Plastic Surgery
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• v.33 no.3
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• pp.330-334
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• 2006

Polymicrobial nature of diabetic foot infection has been well documented in the literature. Initial antibiotic therapy of diabetic foot infection is usually empiric until reliable culture data is shown. This study was carried out to determine the common bacteriological flora of diabetic foot infection and antimicrobial sensitivity pattern in order to enhance possible empiric treatment. The specimens were obtained from wounds of 207 cases of diabetic foot ulcer, and the bacteriological isolation, and antimicrobial susceptibility tests of the isolates were carried out by standard microbiological methods. Staphylococcus aureus was the most common isolate, with 46.2% of recover rate among total bacterial isolated cases. Among gram-negative organisms, Pseudomonas aeruginosa was most common. Gram-positive organisms showed significant susceptibility to clindamycin, trimethoprim/sulfamethoxazole, and levofloxacin, besides vancomycin. Cefoperazone, piperacillin/tazobactam, and amikacin in addition to imipenem were most effective agents compared to gram-negative organisms. Diabetic foot infection requires use of combined antimicrobial therapy for initial management. Our results indicate that the most effective antibiotic combination for diabetic foot infection of Korean patients is clindamycin plus cefoperazone.

• Journal of Microbiology and Biotechnology
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• v.31 no.2
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• pp.189-196
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• 2021

Periplanetasin-2 from cockroach exhibits broad-spectrum antimicrobial activity. The underlying antibacterial mechanisms rely on the stimulation of reactive oxygen species overproduction to induce apoptotic cell death. A promising strategy to increase the bioavailability of periplanetasin-2 involves reducing the dose through combination therapy with other antibacterials that show synergistic effects. Thus, the synergistic antibacterial activity of periplanetasin-2 with conventional antibacterial agents and its mechanisms was examined against Escherichia coli in this study. Among the agents tested, the combinations of periplanetasin-2 with vancomycin and chloramphenicol exhibited synergistic effects. Periplanetasin-2 in combination with vancomycin and chloramphenicol demonstrated antibacterial activity through the intracellular oxidative stress response. The combination with vancomycin resulted in the enhancement of bacterial apoptosis-like death, whereas the combination with chloramphenicol enhanced oxidative stress damage. These synergistic interactions of periplanetasin-2 can help broaden the spectrum of conventional antibiotics. The combination of antimicrobial peptides and conventional antibiotics is proposed as a novel perspective on treatments to combat severe bacterial infection.

• Clinical and Experimental Pediatrics
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• v.50 no.1
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• pp.89-92
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• 2007

Burkholderia cepacia is a Gram-negative aerobic bacillus known to cause opportunistic infections in the immune-compromised hosts. This microorganism is strongly virulent and causes a necrotising invasive infection that may lead to death. As B. cepacia is highly resistant to various antimicrobials, combination antimicrobial therapy must be used instead of monotherapy. We report a successful treatment of lung abscess that was naturally caused by B. cepacia in a healthy child, through combination antimicrobial therapy of meropenem and trimethoprim/sulfamethoxazole and operative management.

• Korean Journal of Veterinary Research
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• v.39 no.2
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• pp.376-382
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• 1999

A methicillin-resistant Staphylococcus aureus (MRSA) isolate was recovered from a 9-month-old female Shih-Tzu dog with canine distemper virus infection. We performed in vitro antimicrobial susceptibility test to determine the most effective antimicrobial drug against the isolate and thus, to emphasize its potential clinical importance in animal practices. Isolate was confirmed MRSA by oxacillin agar screening test. The isolate was fully resistant to all $\beta$-lactam antibiotics and was susceptible to glycopeptides. Of the other antibiotics, mupirocin, TMP/SMZ (trimethoprim-sulfamethoxazole), and chloramphenicol showed inhibitory effect at the concentration of 4x MIC. The MICs ranged 0.25->$128{\mu}g/ml$, and MBCs ranged 0.5->$128{\mu}g/ml$. The combined TMP/SMZ with cefamandole or novobiocin showed synergistic effect, whereas the combination of novobiocin plus cefamandole or teicoplanin resulted in antagonistic effects. Although MRSA in animals so far has been reported in the geographically limited countries, at least theoretically, it could be occurred in the future more frequently through either human or animal origin. The use of this combination may be of value in this situation. As with all antimicrobial agents, inappropriate or unnecessarily prolonged therapy may contribute to the emergence of resistance strains and loss of efficacy.

• Tuberculosis and Respiratory Diseases
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• v.67 no.3
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• pp.212-220
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• 2009

Background: Ventilator-associated pneumonia caused by multi-drug resistant Acinetobacter baumannii has been increasing and growing as a threat in intensive care units. Limited therapeutic options have forced clinicians to choose colistin with or without combination of other antibiotics. We tried to compare the effectiveness between colistin monotherapy and combination therapy based on in vitro synergistic tests. Methods: From January 2006 to December 2007 in medical ICU of a tertiary care hospital in Korea, We reviewed the medical records of patients treated with intravenous colistin due to ventilator-associated pneumonia caused by multi-drug resistant Acinetobacter baumannii. Results: A total of 41 patients were analyzed. 22 patients had been treated with colistin monotherapy and 19 patients with colistin and combination antibiotics that were found to have in vitro synergistic effects. Baseline characteristics were similar in both groups but the mean duration of colistin administration was significantly longer in the combination group (19.1${\pm}$11.2 days vs. 12.3${\pm}$6.8 days, p=0.042). There were no significant differences in outcome variables between the two groups. Conclusion: Combination treatment based on the in vitro antimicrobial synergy test did not show better outcomes compared with colistin monotherapy in VAP caused by multi-drug resistant A. baumannii.

• Journal of Pharmacopuncture
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• v.19 no.4
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• pp.312-318
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• 2016

Objectives: Bacterial resistant infections have become a global health challenge and threaten the society's health. Thus, an urgent need exists to find ways to combat resistant pathogens. One promising approach to overcoming bacterial resistance is the use of herbal products. Green tea catechins, the major green tea polyphenols, show antimicrobial activity against resistant pathogens. The present study aimed to investigate the effect of catechins, green tea extract, and methylxanthines in combination with gentamicin against standard and clinical isolates of Staphylococcus aureus (S. aureus) and the standard strain of Pseudomonas aeruginosa (P. aeruginosa). Methods: The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) values of different agents against bacterial strains were determined. The interactions of green tea extract, epigallate catechin, epigallocatechin gallate, two types of methylxanthine, caffeine, and theophylline with gentamicin were studied in vitro by using a checkerboard method and calculating the fraction inhibitory concentration index (FICI). Results: The MICs of gentamicin against bacterial strains were in the range of $0.312-320{\mu}g/mL$. The MIC values of both types of catechins were $62.5-250{\mu}g/mL$. Green tea extract showed insufficient antibacterial activity when used alone. Methylxanthines had no intrinsic inhibitory activity against any of the bacterial strains tested. When green tea extract and catechins were combined with gentamicin, the MIC values of gentamicin against the standard strains and a clinical isolate were reduced, and synergistic activities were observed (FICI < 1). A combination of caffeine with gentamicin did not alter the MIC values of gentamicin. Conclusion: The results of the present study revealed that green tea extract and catechins potentiated the antimicrobial action of gentamicin against some clinical isolates of S. aureus and standard P. aeruginosa strains. Therefore, combinations of gentamicin with these natural compounds might be a promising approach to combat microbial resistance.