Journal articles: 'Antibiotic synergy'

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Acar, Jacques F. "ANTIBIOTIC SYNERGY AND ANTAGONISM." Medical Clinics of North America 84, no. 6 (November 2000): 1391–406. http://dx.doi.org/10.1016/s0025-7125(05)70294-7.

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Foweraker, Juliet E., Christian R. Laughton, Derek F. Brown, and Diana Bilton. "Comparison of Methods To Test Antibiotic Combinations against Heterogeneous Populations of Multiresistant Pseudomonas aeruginosa from Patients with Acute Infective Exacerbations in Cystic Fibrosis." Antimicrobial Agents and Chemotherapy 53, no. 11 (August 24, 2009): 4809–15. http://dx.doi.org/10.1128/aac.00269-09.

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ABSTRACT Multiresistant Pseudomonas aeruginosa isolates can chronically infect patients with cystic fibrosis. Acute infective exacerbations are treated with combinations of two antipseudomonal antibiotics. Patients may respond clinically even if the bacteria are resistant, possibly due to antimicrobial synergy. The challenge for testing for synergy in vitro is that there is no standardized method, and the antibiotic susceptibility in a population of P. aeruginosa isolates in a single sputum sample can vary. We therefore compared (i) antibiotic combinations with different examples of resistant bacteria from the same sputum sample and (ii) the results of synergy testing by different methods. Antibiotic synergy was tested by using resistant P. aeruginosa isolates recovered from sputum samples taken just before the start of treatment for an acute infective exacerbation. Several examples of each morphotype of P. aeruginosa were tested by cidal checkerboard, time-kill curve, and multiple-combination bactericidal testing. The isolates were typed by pulsed-field gel electrophoresis (PFGE). The results were compared with the clinical and microbiological responses to 14 days of antibiotic treatment. Forty-four resistant isolates from nine patients were tested. Some P. aeruginosa isolates with the same morphotype and PFGE pulsotype had different results by synergy testing. There was a poor correlation between the results of the different methods of synergy testing, and no one method would have predicted the response to treatment in all patients. The in vitro effects of antibiotic combinations against different isolates from the same sputum sample can vary, and the results depend on the methodology used. The role of combination testing for the treatment of antibiotic-resistant P. aeruginosa in acute exacerbations of chronic infection in patients with cystic fibrosis needs to be reviewed.

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Song, Lisa Yun, Sara D'Souza, Karen Lam, Tina Manzhu Kang, Pamela Yeh, and Jeffrey H. Miller. "Exploring Synergy between Classic Mutagens and Antibiotics To Examine Mechanisms of Synergy and Antibiotic Action." Antimicrobial Agents and Chemotherapy 60, no. 3 (December 28, 2015): 1515–20. http://dx.doi.org/10.1128/aac.02485-15.

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We used classical mutagens in Gram-negativeEscherichia colito study synergies with different classes of antibiotics, test models of antibiotic mechanisms of action, and examine the basis of synergy. We used 4-nitroquinoline 1-oxide (4NQO), zebularine (ZEB), 5-azacytidine (5AZ), 2-aminopurine (2AP), and 5-bromodeoxyuridine (5BrdU) as mutagens (with bactericidal potency of 4NQO > ZEB > 5AZ > 2AP > 5BrdU) and vancomycin (VAN), ciprofloxacin (CPR), trimethoprim (TMP), gentamicin (GEN), tetracycline (TET), erythromycin (ERY), and chloramphenicol (CHL) as antibiotics. We detected the strongest synergies with 4NQO, an agent that oxidizes guanines and ultimately results in double-strand breaks when paired with the bactericidal antibiotics VAN, TMP, CPR, and GEN, but no synergies with the bacteriostatic antibiotics TET, ERY, and CHL. Each of the other mutagens displays synergies with the bactericidal antibiotics to various degrees that reflect their potencies, as well as with some of the other mutagens. The results support recent models showing that bactericidal antibiotics kill bacteria principally by ultimately generating more double-strand breaks than can be repaired. We discuss the synergies seen here and elsewhere as representing dose effects of not the proximal target damage but rather the ultimate resulting double-strand breaks. We also used the results of pairwise tests to place the classic mutagens into functional antibacterial categories within a previously defined drug interaction network.

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Diallo, Kevin, and Alain Dublanchet. "Benefits of Combined Phage–Antibiotic Therapy for the Control of Antibiotic-Resistant Bacteria: A Literature Review." Antibiotics 11, no. 7 (June 22, 2022): 839. http://dx.doi.org/10.3390/antibiotics11070839.

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With the increase in bacterial resistance to antibiotics, more and more therapeutic failures are being reported worldwide. The market for antibiotics is now broken due to the high cost of developing new molecules. A promising solution to bacterial resistance is combined phage–antibiotic therapy, a century-old method that can potentiate existing antibiotics by prolonging or even restoring their activity against specific bacteria. The aim of this literature review was to provide an overview of different phage–antibiotic combinations and to describe the possible mechanisms of phage–antibiotic synergy.

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Wang, Shu, Xiang-Qian Liu, Ok-Hwa Kang, and Dong-Yeul Kwon. "Combination of Sanguisorbigenin and Conventional Antibiotic Therapy for Methicillin-Resistant Staphylococcus aureus: Inhibition of Biofilm Formation and Alteration of Cell Membrane Permeability." International Journal of Molecular Sciences 23, no. 8 (April 11, 2022): 4232. http://dx.doi.org/10.3390/ijms23084232.

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Methicillin-resistant Staphylococcus aureus (MRSA) infection is challenging to eradicate because of antibiotic resistance and biofilm formation. Novel antimicrobial agents and alternative therapies are urgently needed. This study aimed to evaluate the synergy of sanguisorbigenin (SGB) isolated from Sanguisorba officinalis L. with six conventional antibiotics to achieve broad-spectrum antibacterial action and prevent the development of resistance. A checkerboard dilution test and time-to-kill curve assay were used to determine the synergistic effect of SGB combined with antibiotics against MRSA. SGB showed significant synergy with antibiotics and reduced the minimum inhibitory concentration of antibiotics by 2–16-fold. Biofilm inhibition assay, quantitative RT-PCR, crystal violet absorption, and transmission electron microscopy were performed to evaluate the synergy mechanism. The results indicated that SGB could inhibit biofilm formation and alter cell membrane permeability in MRSA. In addition, SGB was found to exhibit quite low cytotoxicity and hemolysis. The discovery of the superiority of SGB suggests that SGB may be an antibiotic adjuvant for use in combination therapy and as a plant-derived antibacterial agent targeting biofilms.

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Itzia Azucena, Rangel-Castañeda, Cruz-Lozano José Roberto, Zermeño-Ruiz Martin, Cortes-Zarate Rafael, Hernández-Hernández Leonardo, Tapia-Pastrana Gabriela, and Castillo-Romero Araceli. "Drug Susceptibility Testing and Synergistic Antibacterial Activity of Curcumin with Antibiotics against Enterotoxigenic Escherichia coli." Antibiotics 8, no. 2 (April 18, 2019): 43. http://dx.doi.org/10.3390/antibiotics8020043.

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Aim: This study investigated the susceptibility of Enterotoxigenic Escherichia coli to curcumin, as well as its synergistic effect with 12 antimicrobial drugs. Methods and Results: Our study shows that curcumin did not affect bacterial growth. The antimicrobial susceptibility of curcumin and antibiotic synergy were identified using disc diffusion on Mueller-Hinton agar. The strain of Enterotoxigenic Escherichia coli used was resistant to Ampicillin, Amoxicillin/Clavulanic acid, Ampicillin/Sulbactam, Ciprofloxacin, and Cefazolin. There was synergy between curcumin and the majority of antibiotics tested. Maximum synergy was observed with combinations of 330 µg/mL curcumin and Ceftazidime, followed by Cefotaxime, Amoxicillin/Clavulanic acid, Ampicillin, Aztreonam, Trimethoprim, Ciprofloxacin, Ceftriaxone, Cefazolin, Tetracycline, and Imipenem. Conclusion: Our findings indicated that curcumin might be useful as a combinatorial strategy to combat the antibiotic resistance of Enterotoxigenic Escherichia coli.

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Vamsi, K. Sreeja, S. Rama Moorthy, N. Mary Hemiliamma, Y. Raja Rathna Reddy, B. Rama Chandra Reddy, J. Deepak, and S. Sravani. "A review of antibiotic synergy in carbapenemase-producing bacteria." Journal of Applied and Natural Science 14, no. 1 (March 20, 2022): 148–62. http://dx.doi.org/10.31018/jans.v14i1.3248.

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The problem of antibiotic resistance has garnered too much attention over the last few decades for posing a global hazard to the clinical handling and the inhibition of several deadly infections caused by bacteria. It burdens the world not only clinically but also economically... Antibiotic agents known as carbapenems are a very effective and typically designated for the treatment of multidrug-resistant (MDR) bacterial infections. To identify a suitable antibiotic combination to be used in vivo, one must be able to determine the synergism between the antibiotics in vitro. Several methods, such as the checkerboard method, multiple-combination bactericidal test, time-kill and E-test, have been used for this purpose. However, the lack of proper standardization procedures, types of bacterial agents, bacterial load, stage of infection and other factors make it very difficult to reproduce or correlate the results with other methods.Carbapenem-destroying lactases, which have recently emerged as mechanisms of resistance, are increasing in number and decreasing the treatment alternatives available. These infections are treated with colistin and tigecycline, but monotherapy may result in clinical breakdown because of a variety of factors. To control these infections, clinicians often choose combinations of drugs over monotherapy. There is an extreme lack of information on synergistic antibiotic combinations accounting for the diverse mechanisms of GNB resistance commonly encountered. The incidence of carbapenem-resistant GNB in Indian articles is also unknown. Therefore, we anticipate that this study may provide methodology for the selection of an appropriate antibiotic combination.

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Hess, Donavon J., Michelle J. Henry-Stanley, and Carol L. Wells. "Antibacterial Synergy of Glycerol Monolaurate and Aminoglycosides in Staphylococcus aureus Biofilms." Antimicrobial Agents and Chemotherapy 58, no. 11 (September 2, 2014): 6970–73. http://dx.doi.org/10.1128/aac.03672-14.

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ABSTRACTGlycerol monolaurate (GML) is a natural surfactant with antimicrobial properties. At ∼0.3 mM, both GML and its component lauric acid were bactericidal for antibiotic-resistantStaphylococcus aureusbiofilms. With the use of MICs of antibiotics obtained from planktonic cells, GML and lauric acid acted synergistically with gentamicin and streptomycin, but not ampicillin or vancomycin, to eliminate detectable viable biofilm bacteria. Images of GML-treated biofilms suggested that GML may facilitate antibiotic interaction with matrix-embedded bacteria.

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Kamal, Fatima, and Jonathan J. Dennis. "Burkholderia cepacia Complex Phage-Antibiotic Synergy (PAS): Antibiotics Stimulate Lytic Phage Activity." Applied and Environmental Microbiology 81, no. 3 (December 1, 2014): 1132–38. http://dx.doi.org/10.1128/aem.02850-14.

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ABSTRACTTheBurkholderia cepaciacomplex (Bcc) is a group of at least 18 species of Gram-negative opportunistic pathogens that can cause chronic lung infection in cystic fibrosis (CF) patients. Bcc organisms possess high levels of innate antimicrobial resistance, and alternative therapeutic strategies are urgently needed. One proposed alternative treatment is phage therapy, the therapeutic application of bacterial viruses (or bacteriophages). Recently, some phages have been observed to form larger plaques in the presence of sublethal concentrations of certain antibiotics; this effect has been termed phage-antibiotic synergy (PAS). Those reports suggest that some antibiotics stimulate increased production of phages under certain conditions. The aim of this study is to examine PAS in phages that infectBurkholderia cenocepaciastrains C6433 and K56-2. Bcc phages KS12 and KS14 were tested for PAS, using 6 antibiotics representing 4 different drug classes. Of the antibiotics tested, the most pronounced effects were observed for meropenem, ciprofloxacin, and tetracycline. When grown with subinhibitory concentrations of these three antibiotics, cells developed a chain-like arrangement, an elongated morphology, and a clustered arrangement, respectively. When treated with progressively higher antibiotic concentrations, both the sizes of plaques and phage titers increased, up to a maximum.B. cenocepaciaK56-2-infectedGalleria mellonellalarvae treated with phage KS12 and low-dose meropenem demonstrated increased survival over controls treated with KS12 or antibiotic alone. These results suggest that antibiotics can be combined with phages to stimulate increased phage production and/or activity and thus improve the efficacy of bacterial killing.

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Brennan, Jennifer, Lalit Jain, Sofia Garman, Ann E. Donnelly, Erik Scott Wright, and Kevin Jamieson. "Sample-efficient identification of high-dimensional antibiotic synergy with a normalized diagonal sampling design." PLOS Computational Biology 18, no. 7 (July 18, 2022): e1010311. http://dx.doi.org/10.1371/journal.pcbi.1010311.

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Antibiotic resistance is an important public health problem. One potential solution is the development of synergistic antibiotic combinations, in which the combination is more effective than the component drugs. However, experimental progress in this direction is severely limited by the number of samples required to exhaustively test for synergy, which grows exponentially with the number of drugs combined. We introduce a new metric for antibiotic synergy, motivated by the popular Fractional Inhibitory Concentration Index and the Highest Single Agent model. We also propose a new experimental design that samples along all appropriately normalized diagonals in concentration space, and prove that this design identifies all synergies among a set of drugs while only sampling a small fraction of the possible combinations. We applied our method to screen two- through eight-way combinations of eight antibiotics at 10 concentrations each, which requires sampling only 2,560 unique combinations of antibiotic concentrations.

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Gildea, Logan, Joseph Atia Ayariga, Junhuan Xu, Robert Villafane, Boakai K. Robertson, Michelle Samuel-Foo, and Olufemi S. Ajayi. "Cannabis sativa CBD Extract Exhibits Synergy with Broad-Spectrum Antibiotics against Salmonella enterica subsp. Enterica serovar typhimurium." Microorganisms 10, no. 12 (November 29, 2022): 2360. http://dx.doi.org/10.3390/microorganisms10122360.

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New generation antibiotics are needed to combat the development of resistance to antimicrobials. One of the most promising new classes of antibiotics is cannabidiol (CBD). It is a non-toxic and low-resistance chemical that can be used to treat bacterial infections. The antibacterial activity of Cannabis sativa L. byproducts, specifically CBD, has been of growing interest in the field of novel therapeutics. As research continues to define and characterize the antibacterial activity that CBD possesses against a wide variety of bacterial species, it is important to examine potential interactions between CBD and common therapeutics such as broad-spectrum antibiotics. In this study it is demonstrated that CBD-antibiotic (combination of CBD and antibiotic) co-therapy can effectively fight Salmonella typhimurium (S. typhimurium) via membrane integrity disruption. This research serves to examine the potential synergy between CBD and three broad-spectrum antibiotics (ampicillin, kanamycin, and polymyxin B) for potential CBD-antibiotic co-therapy. In this study, it is revealed that S. typhimurium growth is inhibited at very low dosages of CBD-antibiotic. This interesting finding demonstrates that CBD and CBD-antibiotic co-therapies are viable novel alternatives to combating S. typhimurium.

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D’Souza, Sara, Justin E. Miller, Jenny Ahn, Raechel Subandi, Daniel Lozano, James Ramirez, Marisa Goff, Christina Davidian, and Jeffrey H. Miller. "The Antibiotic Trimethoprim Displays Strong Mutagenic Synergy with 2-Aminopurine." Antimicrobial Agents and Chemotherapy 63, no. 2 (December 3, 2018): e01577-18. http://dx.doi.org/10.1128/aac.01577-18.

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ABSTRACTWe show that trimethoprim (TMP), an antibiotic in current use, displays a strong synergistic effect on mutagenesis inEscherichia coliwhen paired with the base analog 2-aminopurine (2AP), resulting in a 35-fold increase in mutation frequencies in therpoB-Rifrsystem. Combination therapies are often employed both as antibiotic treatments and in cancer chemotherapy. However, mutagenic effects of these combinations are rarely examined. An analysis of the mutational spectra of TMP, 2AP, and their combination indicates that together they trigger a response via an alteration in deoxynucleoside triphosphate (dNTP) ratios that neither compound alone can trigger. A similar, although less strong, response is seen with the frameshift mutagen ICR191 and 2AP. These results underscore the need for testing the effects on mutagenesis of combinations of antibiotics and chemotherapeutics.

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Stachurska, Xymena, Marta Roszak, Joanna Jabłońska, Małgorzata Mizielińska, and Paweł Nawrotek. "Double-Layer Agar (DLA) Modifications for the First Step of the Phage-Antibiotic Synergy (PAS) Identification." Antibiotics 10, no. 11 (October 26, 2021): 1306. http://dx.doi.org/10.3390/antibiotics10111306.

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The research carried out so far for phage-antibiotic synergy (PAS) differs as regards the technique of modifying the double-layer agar (DLA) method to show the PAS effect on Petri plates, which may contribute to non-uniform research results. Therefore, there is a need to unify the method to effectively detect the PAS effect, at its most basic in vitro test. In this study, bacteriophage T45 and 43 antibiotics belonging to different antibiotic classes were used. Seven different DLA method modifications were tested, in terms of antibiotic addition placement and presence or absence of the base agar. The overall number of phage plaques per plate mainly depended on the antibiotic used. Differences in plaque quantity depended on the type of the DLA method modification. The largest total number of plaques was obtained by the addition of an antibiotic to a bottom agar with the presence of a top agar. This indicates that even though an antibiotic could manifest the PAS effect by a standard disk method, it would be worth examining if the effect is equally satisfactory when applying antibiotics directly into the agar, with regards to using the same bacteriophage and bacterial host.

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Park, Myungseo, Liz Horn, Victoria Lappi, Dave Boxrud, Craig Hedberg, and Byeonghwa Jeon. "Antimicrobial Synergy between Aminoglycosides and Licorice Extract in Listeria monocytogenes." Pathogens 11, no. 4 (April 6, 2022): 440. http://dx.doi.org/10.3390/pathogens11040440.

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Listeria monocytogenes is a foodborne pathogen that can develop serious invasive infections. Among foodborne pathogens, L. monocytogenes exhibits the highest case fatality despite antibiotic treatment, suggesting the current therapy should be improved. Although ampicillin and gentamicin are used as a combination therapy to treat listeriosis, our results showed there is no synergy between the two antibiotics. We discovered that aqueous extract of licorice generated significant antimicrobial synergy when combined with aminoglycosides, such as gentamicin, in L. monocytogenes. In the presence of 1 mg/mL licorice extract, for instance, the minimum inhibitory concentration (MIC) of gentamicin was reduced by 32-fold. Moreover, antimicrobial synergy with licorice extract made gentamicin-resistant clinical isolates of L. monocytogenes susceptible to gentamicin. Given the common use of licorice as a food sweetener in Western countries and a herb in Oriental medicine, our findings suggest that licorice extract can be potentially used as an antibiotic adjuvant to improve the efficacy of antimicrobial treatment of listeriosis.

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McCafferty, Dewey G., Predrag Cudic, Michael K. Yu, Douglas C. Behenna, and Ryan Kruger. "Synergy and duality in peptide antibiotic mechanisms." Current Opinion in Chemical Biology 3, no. 6 (December 1999): 672–80. http://dx.doi.org/10.1016/s1367-5931(99)00025-3.

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Černohorská, L., and M. Votava. "Antibiotic synergy against biofilm-forming Pseudomonas aeruginosa." Folia Microbiologica 53, no. 1 (January 2008): 57–60. http://dx.doi.org/10.1007/s12223-008-0008-z.

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Landersdorfer, Cornelia B., Neang S. Ly, Hongmei Xu, Brian T. Tsuji, and Jürgen B. Bulitta. "Quantifying Subpopulation Synergy for Antibiotic Combinations via Mechanism-Based Modeling and a Sequential Dosing Design." Antimicrobial Agents and Chemotherapy 57, no. 5 (March 11, 2013): 2343–51. http://dx.doi.org/10.1128/aac.00092-13.

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ABSTRACTQuantitative modeling of combination therapy can describe the effects of each antibiotic against multiple bacterial populations. Our aim was to develop an efficient experimental and modeling strategy that evaluates different synergy mechanisms using a rapidly killing peptide antibiotic (nisin) combined with amikacin or linezolid as probe drugs. Serial viable counts over 48 h were obtained in time-kill experiments with all three antibiotics in monotherapy against a methicillin-resistantStaphylococcus aureusUSA300 strain (inoculum, 108CFU/ml). A sequential design (initial dosing of 8 or 32 mg/liter nisin, switched to amikacin or linezolid at 1.5 h) assessed the rate of killing by amikacin and linezolid against nisin-intermediate and nisin-resistant populations. Simultaneous combinations were additionally studied and all viable count profiles comodeled in S-ADAPT and NONMEM. A mechanism-based model with six populations (three for nisin times two for amikacin) yielded unbiased and precise (r= 0.99, slope = 1.00; S-ADAPT) individual fits. The second-order killing rate constants for nisin against the three populations were 5.67, 0.0664, and 0.00691 liter/(mg · h). For amikacin, the maximum killing rate constants were 10.1 h−1against its susceptible and 0.771 h−1against its less-susceptible populations, with 14.7 mg/liter amikacin causing half-maximal killing. After incorporating the effects of nisin and amikacin against each population, no additional synergy function was needed. Linezolid inhibited successful bacterial replication but did not efficiently kill populations less susceptible to nisin. Nisin plus amikacin achieved subpopulation synergy. The proposed sequential and simultaneous dosing design offers an efficient approach to quantitatively characterize antibiotic synergy over time and prospectively evaluate antibiotic combination dosing strategies.

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Kampshoff, Franziska, Mark D. P. Willcox, and Debarun Dutta. "A Pilot Study of the Synergy between Two Antimicrobial Peptides and Two Common Antibiotics." Antibiotics 8, no. 2 (May 9, 2019): 60. http://dx.doi.org/10.3390/antibiotics8020060.

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Background: Frequent and unrestricted use of antibiotics has been associated with the development of antibiotic resistance by microorganisms. Thus, there is a need to find novel antibacterial agents or a combination of agents as the first line of treatment for various infections. This study aimed to investigate the synergy between antimicrobial peptide (AMP) combinations or between AMP-antibiotics combinations using two common pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. Methods: The AMPs melimine, Mel4 and protamine, and antibiotics cefepime and ciprofloxacin were used in this study. The minimum inhibitory concentration (MIC) of each were evaluated against P. aeruginosa and S. aureus strains by a microtiter broth dilution. Based on the MIC of each antimicrobial agent, a checkerboard assay was performed to investigate the synergy between them, which was expressed as the fractional inhibitory concentration (FIC). Results: The combination of melimine and ciprofloxacin showed synergistic activity against antibiotic sensitive or resistant strains of P. aeruginosa and with FIC values ≤0.5. Conclusion: Combinations of AMPs and the fluoroquinolone ciprofloxacin is a promising method for reducing resistance to the fluoroquinolone of P. aeruginosa.

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Montalbán-López, Manuel, Rubén Cebrián, Rosa Galera, Lidia Mingorance, Antonio M. Martín-Platero, Eva Valdivia, Manuel Martínez-Bueno, and Mercedes Maqueda. "Synergy of the Bacteriocin AS-48 and Antibiotics against Uropathogenic Enterococci." Antibiotics 9, no. 9 (September 2, 2020): 567. http://dx.doi.org/10.3390/antibiotics9090567.

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The genus Enterococcus comprises a ubiquitous group of Gram-positive bacteria that can cause diverse health care-associated infections. Their genome plasticity enables easy acquisition of virulence factors as well as antibiotic resistances. Urinary tract infections (UTIs) and catheter-associated UTIs are common diseases caused by enterococci. In this study, Enterococcus strains isolated from UTIs were characterized, showing that the majority were E. faecalis and contained several virulence factors associated to a better colonization of the urinary tract. Their susceptibility against the bacteriocin AS-48 and several antibiotics was tested. AS-48 is a potent circular bacteriocin that causes bacterial death by pore formation in the cell membrane. The interest of this bacteriocin is based on the potent inhibitory activity, the high stability against environmental conditions, and the low toxicity. AS-48 was active at concentrations below 10 mg/L even against antibiotic-resistant strains, whereas these strains showed resistance to, at least, seven of the 20 antibiotics tested. Moreover, the effect of AS-48 combined with antibiotics commonly used to treat UTIs was largely synergistic (with up to 100-fold MIC reduction) and only occasionally additive. These data suggest AS-48 as a potential novel drug to deal with or prevent enterococcal infections.

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Chen, Qingquan, Tejas Dharmaraj, Pamela C. Cai, Elizabeth B. Burgener, Naomi L. Haddock, Andy J. Spakowitz, and Paul L. Bollyky. "Bacteriophage and Bacterial Susceptibility, Resistance, and Tolerance to Antibiotics." Pharmaceutics 14, no. 7 (July 7, 2022): 1425. http://dx.doi.org/10.3390/pharmaceutics14071425.

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Bacteriophages, viruses that infect and replicate within bacteria, impact bacterial responses to antibiotics in complex ways. Recent studies using lytic bacteriophages to treat bacterial infections (phage therapy) demonstrate that phages can promote susceptibility to chemical antibiotics and that phage/antibiotic synergy is possible. However, both lytic and lysogenic bacteriophages can contribute to antimicrobial resistance. In particular, some phages mediate the horizontal transfer of antibiotic resistance genes between bacteria via transduction and other mechanisms. In addition, chronic infection filamentous phages can promote antimicrobial tolerance, the ability of bacteria to persist in the face of antibiotics. In particular, filamentous phages serve as structural elements in bacterial biofilms and prevent the penetration of antibiotics. Over time, these contributions to antibiotic tolerance favor the selection of resistance clones. Here, we review recent insights into bacteriophage contributions to antibiotic susceptibility, resistance, and tolerance. We discuss the mechanisms involved in these effects and address their impact on bacterial fitness.

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Braga, L. C., A. A. M. Leite, K. G. S. Xavier, J. A. Takahashi, M. P. Bemquerer, E. Chartone-Souza, and A. M. A. Nascimento. "Synergic interaction between pomegranate extract and antibiotics against Staphylococcus aureus." Canadian Journal of Microbiology 51, no. 7 (July 1, 2005): 541–47. http://dx.doi.org/10.1139/w05-022.

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We evaluated the interaction between Punica granatum (pomegranate) methanolic extract (PGME) and antibiotics against 30 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). Susceptibility testing of the isolates to PGME and antibiotics was performed by the broth dilution method. Synergic activity was detected between PGME and the 5 antibiotics tested, chloramphenicol, gentamicin, ampicillin, tetracycline, and oxacillin, ranging from 38% to 73%. For some isolates, PGME did not interfere with the action of any of the antibiotics tested. The bactericidal activity of PGME (0.1 × MIC) in combination with ampicillin (0.5 × MIC) was assessed using chosen isolates by time-kill assays, and they confirmed the synergic activity. Using this combination, cell viability was reduced by 99.9% and 72.5% in MSSA and MRSA populations, respectively. PGME increased the post-antibiotic effect (PAE) of ampicillin from 3 to 7 h. In addition, PGME demonstrated the potential to either inhibit the efflux pump NorA or to enhance the influx of the drug. The detection of in vitro variant colonies of S. aureus resistant to PGME was low and they did not survive. In conclusion, PGME dramatically enhanced the activity of all antibiotics tested, and thus, offers an alternative for the extension of the useful lifetime of these antibiotics.Key words: Staphylococcus aureus, antibiotic-resistance, synergy, NorA, Punica granatum.

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Hassan, D. M., S. M. Elnagdy, A. Abu Taleb, B. A. Gomaa, and N. S. Soliman. "Synergy of Herbal Oil Extracts/Antibiotic Combinations in Drug- Resistant Uropathogenic E. coli." Journal of Pure and Applied Microbiology 14, no. 2 (June 11, 2020): 1479–85. http://dx.doi.org/10.22207/jpam.14.2.45.

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Woźniak, Agata, Beata Kruszewska, Michał Karol Pierański, Michał Rychłowski, and Mariusz Grinholc. "Antimicrobial Photodynamic Inactivation Affects the Antibiotic Susceptibility of Enterococcus spp. Clinical Isolates in Biofilm and Planktonic Cultures." Biomolecules 11, no. 5 (May 5, 2021): 693. http://dx.doi.org/10.3390/biom11050693.

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Enterococcus faecium and Enterococcus faecalis are opportunistic pathogens that can cause a vast variety of nosocomial infections. Moreover, E. faecium belongs to the group of ESKAPE microbes, which are the main cause of hospital-acquired infections and are especially difficult to treat because of their resistance to many antibiotics. Antimicrobial photodynamic inactivation (aPDI) represents an alternative to overcome multidrug resistance problems. This process requires the simultaneous presence of oxygen, visible light, and photosensitizing compounds. In this work, aPDI was used to resensitize Enterococcus spp. isolates to antibiotics. Antibiotic susceptibility testing according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations was combined with synergy testing methods recommended by the American Society for Microbiology. Two clinical isolates, E. faecalis and E. faecium, were treated with a combination of aPDI utilizing rose bengal (RB) or fullerene (FL) derivative as photosensitizers, antimicrobial blue light (aBL), and 10 recommended antibiotics. aPDI appeared to significantly impact the survival rate of both isolates, while aBL had no significant effect. The synergy testing results differed between strains and utilized methods. Synergy was observed for RB aPDI in combination with gentamycin, ciprofloxacin and daptomycin against E. faecalis. For E. faecium, synergy was observed between RB aPDI and gentamycin or ciprofloxacin, while for RB aPDI with vancomycin or daptomycin, antagonism was observed. A combination of FL aPDI gives a synergistic effect against E. faecalis only with imipenem. Postantibiotic effect tests for E. faecium demonstrated that this isolate exposed to aPDI in combination with gentamycin, streptomycin, tigecycline, doxycycline, or daptomycin exhibits delayed growth in comparison to untreated bacteria. The results of synergy testing confirmed the effectiveness of aPDI in resensitization of the bacteria to antibiotics, which presents great potential in the treatment of infections caused by multidrug-resistant strains.

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Duong, Leora, Steven P. Gross, and Albert Siryaporn. "A novel antibacterial strategy: histone and antimicrobial peptide synergy." Microbial Cell 7, no. 11 (November 2, 2020): 309–11. http://dx.doi.org/10.15698/mic2020.11.736.

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The rate at which antibiotics are discovered and developed has stagnated; meanwhile, antibacterial resistance continually increases and leads to a plethora of untreatable and deadly infections worldwide. Therefore, there is a critical need to develop new antimicrobial strategies to combat this alarming reality. One approach is to understand natural antimicrobial defense mechanisms that higher-level organisms employ in order to kill bacteria, potentially leading to novel antibiotic therapeutic approaches. Mammalian histones have long been reported to have antibiotic activity, with the first observation of their antibacterial properties reported in 1942. However, there have been doubts about whether histones could truly have any such role in the animal, predominantly based on two issues: they are found in the nucleus (so are not in a position to encounter bacteria), and their antibiotic activity in vitro has been relatively weak in physiological conditions. More recent studies have addressed both sets of concerns. Histones are released from cells as part of neutrophil extracellular traps (NETs) and are thus able to encounter extracellular bacteria. Histones are also present intracellularly in the cytoplasm attached to lipid droplets, positioning them to encounter cytosolic bacteria. Our recent work (Doolin et al., 2020, Nat Commun), which is discussed here, shows that histones have synergistic antimicrobial activities when they are paired with antimicrobial peptides (AMPs), which form pores in bacterial membranes and co-localize with histones in NETs. The work demonstrates that histones enhance AMP-mediated pores, impair bacterial membrane recovery, depolarize the bacterial proton gradient, and enter the bacterial cytoplasm, where they restructure the chromosome and inhibit transcription. Here, we examine potential mechanisms that are responsible for these outcomes.

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Ivanchenko, D. A., and L. M. Hrytsenko. "In vitro synergy testing of prodigiosin in combination with inhibitors of cell wall synthesis against Mycobacterium smegmatis." Regulatory Mechanisms in Biosystems 11, no. 1 (February 3, 2020): 127–32. http://dx.doi.org/10.15421/022019.

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The cell wall is not a target of currently used therapeutics as Mycobacterium are considered naturally resistant to most β-lactam antibiotics. Therefore, combinations of conventional antibiotics with antibiotic activity-enhancing compounds offer a productive treatment strategy and address the widespread emergence of antibiotic-resistant strains. The first area of research was the study of a comparative analysis of disk diffusion testing and the broth dilution method for evaluating the susceptibility of M. smegmatis to antimicrobial agents. A comparative analysis of the susceptibility to antimicrobial agents alone showed that M. smegmatis was the most susceptible to ceftriaxone and kanamycin, and moderately sensitive to vancomycin and prodigiosin. Compared to the susceptibility of the antibacterial combinations, the isolate was not susceptible to antibacterial combinations with prodigiosin in disk diffusion testing. The second area of research was the study of the synergic activity of prodigiosin of S. marcescens and inhibitors of cell wall synthesis manifested by their simultaneous effect on M. smegmatis. The greatest increase in the sensitivity of test-culture of mycobacteria occurred with ampicillin, benzylpenicillin, cephazolin and ceftriaxone in combination with prodigiosin of S. marcescens. The presented combination of antibiotics and prodigiosin reduce the required concentration of the antibiotic and by amplifying the effect of compounds inhibiting cell wall synthesis, thereby giving lower FICI values. These data indicate the possibility of using prodigiosin as a promising candidate for the development of "accompaniment-preparations" for antibiotics for the additional therapy of infectious diseases caused by Mycobacterium spp. and can suspend the likelihood of developing resistance to antibiotics. The cell wall is not a target of currently used therapeutics as Mycobacterium are considered naturally resistant to most β-lactam antibiotics. Therefore, combinations of conventional antibiotics with antibiotic activity-enhancing compounds offer a productive treatment strategy and address the widespread emergence of antibiotic-resistant strains. The first area of research was the study of a comparative analysis of disk diffusion testing and the broth dilution method for evaluating the susceptibility of M. smegmatis to antimicrobial agents. A comparative analysis of the susceptibility to antimicrobial agents alone showed that M. smegmatis was the most susceptible to ceftriaxone and kanamycin, and moderately sensitive to vancomycin and prodigiosin. Compared to the susceptibility of the antibacterial combinations, the isolate was not susceptible to antibacterial combinations with prodigiosin in disk diffusion testing. The second area of research was the study of the synergic activity of prodigiosin of S. marcescens and inhibitors of cell wall synthesis manifested by their simultaneous effect on M. smegmatis. The greatest increase in the sensitivity of test-culture of mycobacteria occurred with ampicillin, benzylpenicillin, cephazolin and ceftriaxone in combination with prodigiosin of S. marcescens. The presented combination of antibiotics and prodigiosin reduce the required concentration of the antibiotic and by amplifying the effect of compounds inhibiting cell wall synthesis, thereby giving lower FICI values. These data indicate the possibility of using prodigiosin as a promising candidate for the development of "accompaniment-preparations" for antibiotics for the additional therapy of infectious diseases caused by Mycobacterium spp. and can suspend the likelihood of developing resistance to antibiotics.

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Iqbal, Mochammad, Erlia Narulita, Fiqih Zahra, and Siti Murdiyah. "Effect of Phage-Antibiotic Synergism (PAS) in increasing antibiotic inhibition of bacteria caused of foodborne diseases." Journal of Infection in Developing Countries 14, no. 05 (May 31, 2020): 488–93. http://dx.doi.org/10.3855/jidc.12094.

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Introduction: Food contaminated with pathogenic bacteria is one of the most harmful things that can even threaten human life. Over time, these pathogenic bacteria are increasingly resistant to antibiotics. Continuous use of synthetic preservatives will also have an adverse effect. This study was conducted to evaluate the synergy of bacteriophage and antibiotics in increasing antibiotics inhibition to the bacteria that cause foodborne disease. Methodology: The test was performed by plaque assay and paper disc diffusion on NA medium in the same petri dish. The combination was incubated for 24 hours at 37ºC. An antibiotic inhibition on a non-bacteriophage test showed cefadroxil could only inhibit P21B bacteria. Results: Cefadroxil inhibition in the PAS test showed that these antibiotics could inhibit some other foodborne disease bacteria (Salmonella spp., Staphylococcus aureus, and Escherichia coli). The inhibitory observed from the clear zone located around the disc paper. Conclusion: These results provide useful information to reduce the risk of antibiotic resistance in humans and foods.

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Comeau, André M., Françoise Tétart, Sabrina N. Trojet, Marie-Françoise Prère, and H. M. Krisch. "Phage-Antibiotic Synergy (PAS): β-Lactam and Quinolone Antibiotics Stimulate Virulent Phage Growth." PLoS ONE 2, no. 8 (August 29, 2007): e799. http://dx.doi.org/10.1371/journal.pone.0000799.

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Ellis, Jenna-Claire, Reynolds P. Ross, and Colin Hill. "Nisin Z and lacticin 3147 improve efficacy of antibiotics against clinically significant bacteria." Future Microbiology 14, no. 18 (December 2019): 1573–87. http://dx.doi.org/10.2217/fmb-2019-0153.

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Aim: To determine if bacteriocins improve antibiotic efficacy. Materials & methods: Deferred antagonism assays identified bacteriocins with activity. Growth curves and time kill assays demonstrated bactericidal activity of antimicrobial combinations, and checkerboard assays confirmed synergy. Methicillin-resistant Staphylococcus aureus-infected porcine skin model determined ex vivo efficacy. Results: Subinhibitory concentrations of lacticin with penicillin or vancomycin resulted in complete growth inhibition of strains and the improved inhibitory effect was apparent after 1 h. Nisin with methicillin proved more effective against methicillin-resistant Staphylococcus aureus than either antimicrobial alone, revealing partial synergy and significantly reduced pathogen numbers on porcine skin after 3 h compared with minimal inhibition for either antimicrobial alone. Conclusion: Nisin Z and lacticin 3147 may support the use of certain antibiotics and revive ineffective antibiotics.

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Song, Lisa Yun, Sara D'Souza, Karen Lam, Tina Manzhu Kang, Pamela Yeh, and Jeffrey H. Miller. "Erratum for Song et al., Exploring Synergy between Classic Mutagens and Antibiotics To Examine Mechanisms of Synergy and Antibiotic Action." Antimicrobial Agents and Chemotherapy 60, no. 4 (March 25, 2016): 2600. http://dx.doi.org/10.1128/aac.00429-16.

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Hamdani, Muhammad Jen, Natsir Djide, and Mansyur Arif. "Incidence of Klebsiella pneumoniae producing Metallo Beta-Lactamase (MBL) at RSUP Dr. Wahidin Sudirohusodo Makassar." Sasambo Journal of Pharmacy 3, no. 1 (April 28, 2022): 6–10. http://dx.doi.org/10.29303/sjp.v3i1.111.

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Bacterial resistance to antibiotic is one of the factors triggering infection therapy failure. This study was conducted to determine the prevalence of carbapenem-resistance Klebsiella pneumoniae infection and the phenotype of carbapenem-resistant Metallo-Beta-Lactamase (MBL)-producing Klebsiella pneumoniae isolates at RSUP Dr. Wahidin Sudirohusodo Makassar. This study included Klebsiella pneumoniae identification on each infectious patient’s isolates. The sensitivity test of antibiotics, phenotype confirmatory test, and MBL phenotypic test were conducted using agar diffusion Kirby-Bauer, Vitek-2-Compact, and Double Disc Synergy Test (DDST) method, respectively. As the result, the antibiotic sensitivity test using the Vitek-2-Compact method on 50 clinical samples (pus, sputum, blood. tissue, urine, brain fluid, and feces) found that 10 isolates (20%) were resistant to carbapenem. The phenotypic test using the Double Disc Synergy Test (DDST) method found that carbapenem-resistant isolates caused by the production of Metallo Beta Lactamase (MBL) enzymes were 2 isolates or 20% of the total carbapenem-resistant isolates.

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Kristich, Christopher J., Dušanka Djorić, and Jaime L. Little. "Genetic Basis for Vancomycin-Enhanced Cephalosporin Susceptibility in Vancomycin-Resistant Enterococci Revealed Using Counterselection with Dominant-Negative Thymidylate Synthase." Antimicrobial Agents and Chemotherapy 58, no. 3 (December 23, 2013): 1556–64. http://dx.doi.org/10.1128/aac.02001-13.

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ABSTRACTAntibiotic-resistant enterococci are major causes of hospital-acquired infections. All enterococci are intrinsically resistant to most cephalosporins, antibiotics in the beta-lactam family that impair peptidoglycan synthesis by inactivating the transpeptidases responsible for cross-linking. In addition, clinical isolates of enterococci often possess acquired resistance to vancomycin, a glycopeptide antibiotic that impairs peptidoglycan biosynthesis by a mechanism distinct from that of the beta-lactams, namely, by binding to thed-Ala-d-Ala termini found in peptidoglycan precursors to prevent their utilization by biosynthetic transglycosylases. Antimicrobial synergism between vancomycin and beta-lactams against vancomycin-resistant enterococci was originally described decades ago, but the genetic basis for synergy has remained unknown. Because a complete understanding of the mechanism underlying synergy between vancomycin and beta-lactams might suggest new targets or strategies for therapeutic intervention against antibiotic-resistant enterococci, we explored the genetic basis for synergy between vancomycin and cephalosporins inEnterococcus faecalis. To do so, we developed a counterselection strategy based on a dominant-negative mutant of thymidylate synthase and implemented this approach to create a panel of mutants in vancomycin-resistantE. faecalis. Our results confirm that vancomycin promotes synergy by inducing expression of thevanresistance genes, as a mutant in which thevangenes are expressed in the absence of vancomycin exhibits susceptibility to cephalosporins. Further, we show that peptidoglycan precursors substituted withd-Ala-d-Lac are not required for vancomycin-enhanced cephalosporin sensitivity. Instead, production of thed,d-carboxypeptidase VanYBis both necessary and sufficient to dramatically sensitizeE. faecalisto cephalosporins.

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Igbinosa, Etinosa O., Emmanuel E. Odjadjare, Isoken H. Igbinosa, Phillips O. Orhue, May N. O. Omoigberale, and Napoleon I. Amhanre. "Antibiotic Synergy Interaction against Multidrug-ResistantPseudomonas aeruginosaIsolated from an Abattoir Effluent Environment." Scientific World Journal 2012 (2012): 1–5. http://dx.doi.org/10.1100/2012/308034.

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Pseudomonas aeruginosais an opportunistic pathogen in environmental waters with a high prevalence of multidrug resistance. In this study the synergistic efficacy of synergy antibiotic combinations in multidrug-resistantP. aeruginosastrains isolated from an abattoir effluent was investigated. Water samples were processed using membrane filtration;Pseudomonaswas isolated with Pseudomonas Isolation Agar and confirmed using polymerase chain reaction with specie-specific primer. Susceptibility studies andin vitrosynergy interaction testing were carried out, employing agar dilution and Etest procedure, respectively. Resistance was noted for clinically relevant antipseudomonal agents tested. Finding from antibiotic synergy interaction studies revealed that cefepime, imipenem, and meropenem combined with amikacin resulted in statistically significant (P<0.0001)in vitroantibiotics synergy interaction, indicating the possible use of this regimen in treatment of pseudomonal infections.

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Nazarov, Pavel A. "MDR Pumps as Crossroads of Resistance: Antibiotics and Bacteriophages." Antibiotics 11, no. 6 (May 30, 2022): 734. http://dx.doi.org/10.3390/antibiotics11060734.

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At present, antibiotic resistance represents a global problem in modern medicine. In the near future, humanity may face a situation where medicine will be powerless against resistant bacteria and a post-antibiotic era will come. The development of new antibiotics is either very expensive or ineffective due to rapidly developing bacterial resistance. The need to develop alternative approaches to the treatment of bacterial infections, such as phage therapy, is beyond doubt. The cornerstone of bacterial defense against antibiotics are multidrug resistance (MDR) pumps, which are involved in antibiotic resistance, toxin export, biofilm, and persister cell formation. MDR pumps are the primary non-specific defense of bacteria against antibiotics, while drug target modification, drug inactivation, target switching, and target sequestration are the second, specific line of their defense. All bacteria have MDR pumps, and bacteriophages have evolved along with them and use the bacteria’s need for MDR pumps to bind and penetrate into bacterial cells. The study and understanding of the mechanisms of the pumps and their contribution to the overall resistance and to the sensitivity to bacteriophages will allow us to either seriously delay the onset of the post-antibiotic era or even prevent it altogether due to phage-antibiotic synergy.

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Rand, K. H., H. J. Houck, P. Brown, and D. Bennett. "Reproducibility of the microdilution checkerboard method for antibiotic synergy." Antimicrobial Agents and Chemotherapy 37, no. 3 (March 1, 1993): 613–15. http://dx.doi.org/10.1128/aac.37.3.613.

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Winstanley, T. G., and J. G. M. Hastings. "Penicillin-aminoglycoside synergy and post-antibiotic effect for enterococci." Journal of Antimicrobial Chemotherapy 23, no. 2 (1989): 189–99. http://dx.doi.org/10.1093/jac/23.2.189.

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Sunnerhagen, Torgny, Bo Nilson, and Magnus Rasmussen. "Antibiotic synergy against viridans streptococci isolated in infective endocarditis." International Journal of Antimicrobial Agents 45, no. 5 (May 2015): 550–51. http://dx.doi.org/10.1016/j.ijantimicag.2015.01.002.

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Bodey, G. P. "Synergy. Should it determine antibiotic selection in neutropenic patients?" Archives of Internal Medicine 145, no. 11 (November 1, 1985): 1964–66. http://dx.doi.org/10.1001/archinte.145.11.1964.

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Adeniji, Oluwaseun Ola, Nolonwabo Nontongana, Janet Chiyem Okoh, and Anthony Ifeanyi Okoh. "The Potential of Antibiotics and Nanomaterial Combinations as Therapeutic Strategies in the Management of Multidrug-Resistant Infections: A Review." International Journal of Molecular Sciences 23, no. 23 (November 30, 2022): 15038. http://dx.doi.org/10.3390/ijms232315038.

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Antibiotic resistance has become a major public health concern around the world. This is exacerbated by the non-discovery of novel drugs, the development of resistance mechanisms in most of the clinical isolates of bacteria, as well as recurring infections, hindering disease treatment efficacy. In vitro data has shown that antibiotic combinations can be effective when microorganisms are resistant to individual drugs. Recently, advances in the direction of combination therapy for the treatment of multidrug-resistant (MDR) bacterial infections have embraced antibiotic combinations and the use of nanoparticles conjugated with antibiotics. Nanoparticles (NPs) can penetrate the cellular membrane of disease-causing organisms and obstruct essential molecular pathways, showing unique antibacterial mechanisms. Combined with the optimal drugs, NPs have established synergy and may assist in regulating the general threat of emergent bacterial resistance. This review comprises a general overview of antibiotic combinations strategies for the treatment of microbial infections. The potential of antibiotic combinations with NPs as new entrants in the antimicrobial therapy domain is discussed.

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Ahmad, Manzoor, Mukhtiar Hassan, Anwar Khalid, Imran Tariq, Muhammad Hassham Hassan Bin Asad, Abdul Samad, Qaisar Mahmood, and Ghulam Murtaza. "Prevalence of Extended Spectrumβ-Lactamase and Antimicrobial Susceptibility Pattern of Clinical Isolates ofPseudomonasfrom Patients of Khyber Pakhtunkhwa, Pakistan." BioMed Research International 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/6068429.

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Majority of gram negative pathogenic bacteria are responsible for extended spectrumβ-lactamases (ESBLs) production, which show resistance to some newer generation of antibiotics. The study was aimed at evaluating the prevalence of ESBL and antibiotic susceptibility pattern ofPseudomonasisolates collected during 2010 to 2014 from tertiary care hospitals of Peshawar, Pakistan. Out of 3450 samples, 334Pseudomonasspp. isolates comprised of 232 indoor and 102 outdoor patients were obtained from different specimens and their susceptibility pattern was determined against 20 antibiotics. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer agar diffusion method and ESBL production was detected by Synergy Disc Diffusion technique. The mean age group of the patients was 29.9 + 9.15 years. Meronem showed best activity (91.02%) from class carbapenem,β-lactam andβ-lactamase inhibitors exhibited 69.16% activity, and doxycycline had a diminished activity (10.18%) toPseudomonasspp. Outdoor isolates were more resistant than the indoor and during the course of the study the sensitivity rate of antibiotics was gradually reducing. ESBL production was observed in 44.32% while the remaining was non-ESBL. The moderate active antibiotics were amikacin (50.7%), SCF (51.4%), TZP (52.7%), and MXF (54.1%) among ESBL producing isolates. Lack of antibiotic policy, irrational uses (3GCs particularly), and the emergence of antibiotic resistant organisms in hospitals may be causes of high antibiotic resistance.

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Simon, Kevin, Wolfgang Pier, Alex Krüttgen, and Hans-Peter Horz. "Synergy between Phage Sb-1 and Oxacillin against Methicillin-Resistant Staphylococcus aureus." Antibiotics 10, no. 7 (July 13, 2021): 849. http://dx.doi.org/10.3390/antibiotics10070849.

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Methicillin-resistant Staphylococcus aureus (MRSA) is a notorious pathogen responsible for not only a number of difficult-to-treat hospital-acquired infections, but also for infections that are community- or livestock-acquired. The increasing lack of efficient antibiotics has renewed the interest in lytic bacteriophages (briefly phages) as additional antimicrobials against multi-drug resistant bacteria, including MRSA. The aim of this study was to test the hypothesis that a combination of the well-known and strictly lytic S. aureus phage Sb-1 and oxacillin, which as sole agent is ineffective against MRSA, exerts a significantly stronger bacterial reduction than either antimicrobial alone. Eighteen different MRSA isolates and, for comparison, five MSSA and four reference strains were included in this study. The bacteria were challenged with a combination of varying dosages of the phage and the antibiotic in liquid medium using five different antibiotic levels and four different viral titers (i.e., multiplicity of infections (MOIs) ranging from 10−5 to 10). The dynamics of the cell density changes were determined via time-kill assays over 16 h. Positive interactions between both antimicrobials in the form of facilitation, additive effects, or synergism were observed for most S. aureus isolates. These enhanced antibacterial effects were robust with phage MOIs of 10−1 and 10 irrespective of the antibiotic concentrations, ranging from 5 to 100 µg/mL. Neutral effects between both antimicrobials were seen only with few isolates. Importantly, antagonism was a rare exception. As a conclusion, phage Sb-1 and oxacillin constitute a robust heterologous antimicrobial pair which extends the efficacy of a phage-only approach for controlling MRSA.

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Maisuria, Vimal B., Zeinab Hosseinidoust, and Nathalie Tufenkji. "Polyphenolic Extract from Maple Syrup Potentiates Antibiotic Susceptibility and Reduces Biofilm Formation of Pathogenic Bacteria." Applied and Environmental Microbiology 81, no. 11 (March 27, 2015): 3782–92. http://dx.doi.org/10.1128/aem.00239-15.

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ABSTRACTPhenolic compounds are believed to be promising candidates as complementary therapeutics. Maple syrup, prepared by concentrating the sap from the North American maple tree, is a rich source of natural and process-derived phenolic compounds. In this work, we report the antimicrobial activity of a phenolic-rich maple syrup extract (PRMSE). PRMSE exhibited antimicrobial activity as well as strong synergistic interaction with selected antibiotics against Gram-negative clinical strains ofEscherichia coli,Proteus mirabilis, andPseudomonas aeruginosa. Among the phenolic constituents of PRMSE, catechol exhibited strong synergy with antibiotics as well as with other phenolic components of PRMSE against bacterial growth. At sublethal concentrations, PRMSE and catechol efficiently reduced biofilm formation and increased the susceptibility of bacterial biofilms to antibiotics. In an effort to elucidate the mechanism for the observed synergy with antibiotics, PRMSE was found to increase outer membrane permeability of all bacterial strains and effectively inhibit efflux pump activity. Furthermore, transcriptome analysis revealed that PRMSE significantly repressed multiple-drug resistance genes as well as genes associated with motility, adhesion, biofilm formation, and virulence. Overall, this study provides a proof of concept and starting point for investigating the molecular mechanism of the reported increase in bacterial antibiotic susceptibility in the presence of PRMSE.

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WOLSKA, KRYSTYNA I., KATARZYNA GRZEŚ, and ANNA KUREK. "Synergy between Novel Antimicrobials and Conventional Antibiotics or Bacteriocins." Polish Journal of Microbiology 61, no. 2 (2012): 95–104. http://dx.doi.org/10.33073/pjm-2012-012.

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Due to the alarming spread of resistance to classic antimicrobial agents, innovative therapeutic methods to combat antibiotic-resistant bacterial pathogens are urgently required. This minireview examines the enhancement of antibiotic efficacy by their combination with new antimicrobials, such as plant-derived compounds, metal ions and nanoparticles and bacteriophage lytic enzymes. The mechanisms of the observed synergy are also described. The promising results of basic research indicate that in future, combined therapy may be applied in human and veterinary medicine, agriculture and the food industry to combat bacterial pathogens.

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Okoko, Irene Mkavi, Naomi Maina, Daniel Kiboi, and John Kagira. "β-lactam resistance in bacteria associated with subclinical mastitis in goats in Thika Subcounty, Kenya." July-2020 13, no. 7 (2020): 1448–56. http://dx.doi.org/10.14202/vetworld.2020.1448-1456.

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Aim: This study determined the resistance pattern to β-lactam antibiotics of bacteria isolated from goats with subclinical mastitis in Thika subcounty, Kenya. We also administered a questionnaire to assess the risk factors associated with the occurrence of resistance to commonly used antibiotics. Materials and Methods: We collected milk samples from 110 lactating dairy goats in Thika subcounty to screen for subclinical mastitis using the California mastitis test. Bacterial isolation and identification were performed according to colony morphology, the hemolytic pattern on sheep blood agar, lactose fermentation on MacConkey plates, Gram staining, and standard biochemical tests. The antibiotic susceptibility of the isolates was determined by the agar disk diffusion method using penicillin G, cephalexin, cefoxitin, and cefotaxime antibiotic disks. The double-disk synergy test using amoxicillin-clavulanic acid was employed as a confirmatory test for extended-spectrum β-lactamase (ESBL) production. Fisher's exact test was used to determine the risk factors associated with the occurrence of antibiotic resistance (p≤0.05 was considered significant). Results: Of the 110 dairy goats sampled, 72.7% (80) were positive for subclinical mastitis. Isolation and identification of the bacteria from the positive samples yielded 149 bacteria isolates, including Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter spp., Yersinia spp., coagulase-negative staphylococci, and Escherichia coli. A high percentage (76.5%, 114/149) of the bacterial isolates was resistant to at least one of the tested antibiotics. At least 56/106 isolates (52.8%) showing cross-resistance to the β-lactam antibiotics were resistant to all four of the tested antibiotics, while only one isolate was resistant to three antibiotics (penicillin G, cephalexin, and cefoxitin). The double-disk synergy test confirmed that none of the isolates possessed ESBLs. Pre- and post-milking practices (p=0.0336) were found to be significantly associated with the occurrence of antibiotic resistance. Conclusion: A large proportion of the goats in our study cohort were infected with β-lactam-resistant bacteria associated with subclinical mastitis. Because the identified bacteria are of zoonotic importance, further studies should be undertaken to determine the transmission dynamics between humans and livestock and to identify novel intervention strategies.

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Chitrabanu, N. Ashwin, and Shrikara Mallya. "Identification, Speciation and Antibiogram along with Detection of Metallo Beta-lactamase Production in Acinetobacter Isolated from Clinical Samples in a Tertiary Care Hospital." Journal of Pure and Applied Microbiology 15, no. 2 (May 28, 2021): 839–44. http://dx.doi.org/10.22207/jpam.15.2.38.

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Acinetobacter species are gram negative non fermenters, which are important nosocomial pathogens involved in various outbreaks in hospitals due to widespread resistance to majority antibiotics. The aim of this study is to speciate Acinetobacter isolated from clinical samples, to assess the antibiotic sensitivity pattern and to detect the production of metallo-β-lactamase by double disc synergy test. The study was conducted in the department of microbiology, A. J Institute of Medical Sciences. All clinical samples were subjected to gram stain & cultured; the Acinetobacter isolates obtained were subjected to antibiogram. Those isolates that showed Imipenem resistant were further tested for production of metallo-β-lactamase by double disc synergy test. Out of 6625 culture positive isolates, 414 (36.1%) were identified biochemically to belong to Acinetobacter species. Of the 414 cases, 393 (94.9%) were further identified to be Acinetobacter baumannii and the remaining 21 (5.1%) to be Acinetobacter lwoffi. Acinetobacter lwoffii showed 100% sensitivity to all the drugs. Of the 393 Acinetobacter baumannii isolates 109 (27.7%) showed resistant to Imipenem. Out of these 109 isolates, 65 (59.63%) were positive for metallo-β-lactamase production by double disk synergy test. The speciation is highly demanding and laborious but it’s important to be demonstrated due to difference in the antibiotic susceptibility pattern. Carbapenem resistant Acinetobacter nosocomial strains in ICUs are detected to be more resistant to antibiotics. As shown in this study the metallo-β-lactamase producing A.baumannii isolates were 59.63% and therapeutic options were limited. Therefore early identification of metallo-β-lactamase producers is of great importance to start appropriate treatment and to control the spread.

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Briggs, Simon, Matthew Broom, Eamon Duffy, Richard Everts, Gabrielle Everts, Boris Lowe, Stephen McBride, and Hasan Bhally. "Outpatient continuous-infusion benzylpenicillin combined with either gentamicin or ceftriaxone for enterococcal endocarditis." Journal of Antimicrobial Chemotherapy 76, no. 8 (May 11, 2021): 2168–71. http://dx.doi.org/10.1093/jac/dkab132.

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Abstract Background Treatment regimens requiring multiple daily dosing for enterococcal endocarditis are challenging to deliver in the outpatient setting. Continuous-infusion benzylpenicillin via a 24 h elastomeric infusor, combined with either once-daily gentamicin or ceftriaxone, requires only one nursing encounter daily and is commonly used in New Zealand. Objectives To assess the therapeutic success and adverse antibiotic effects of these regimens. Methods A retrospective observational case series from multiple hospitals of patients aged 15 years or over with enterococcal endocarditis diagnosed between July 2013 and June 2019 who received at least 14 days of outpatient continuous-infusion benzylpenicillin combined with either gentamicin or ceftriaxone for synergy. Results Forty-three episodes of enterococcal endocarditis in 41 patients met inclusion criteria. The primary synergy antibiotic was gentamicin in 20 episodes and ceftriaxone in 23 episodes. For the 41 initial treatment courses, 31 (76%) patients were cured, 3 (7%) patients developed relapsed endocarditis during or following antibiotic treatment and 7 (17%) patients continued with long-term suppressive oral amoxicillin following IV antibiotic treatment. There was no difference in the relapse rate between the two groups (P = 0.59). Seven (35%) adverse antibiotic effects were documented in the gentamicin group and none in the ceftriaxone group (P < 0.01). Two deaths (5%) occurred within the 6 month follow-up period. Conclusions Outpatient treatment of enterococcal endocarditis with continuous-infusion benzylpenicillin combined with either once-daily gentamicin or ceftriaxone following a period of inpatient treatment is usually effective. A significantly higher rate of adverse effects was seen with gentamicin, favouring ceftriaxone as the initial synergy antibiotic.

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Anwar, Muneeza, Hassan Ejaz, Aizza Zafar, and Hamdan Hamid. "Phenotypic Detection of Metallo-Beta-Lactamases in Carbapenem ResistantAcinetobacter baumanniiIsolated from Pediatric Patients in Pakistan." Journal of Pathogens 2016 (2016): 1–6. http://dx.doi.org/10.1155/2016/8603964.

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Multidrug resistantA. baumanniihas emerged as an important and problematic human pathogen as it is the causative agent of several types of infections especially in neonates and immunocompromised patients because they have least capacity to fight against infections. Carbapenems are used as last resort antibiotics for treating these infections but currently resistance against carbapenems due to MBL production is on the rise. The objective of this study was to determine the frequency of antibiotic resistance inA. baumanniiand also to compare the efficacy of combined disk test and double disk synergy test for detection of metallo-beta-lactamases. A total of 112A. baumanniiwere identified from various clinical samples and antibiotic susceptibility profile was determined by Kirby-Bauer Disk Diffusion method. Out of 112, 66 (58.9%) isolates were resistant to both imipenem and meropenem (OXOID). These resistant isolates were tested for carbapenemase production, and 55 (83.3%) were carbapenemase producers by Modified Hodge Test. These isolates were further tested for MBL production by combined disk test and double disk synergy test. Out of 66, 49 isolates were positive by both methods, CDT and DDST, and only one isolate was detected as negative (with kappa value = 0.038). All MBL producing strains showed remarkable resistance to cephalosporins, fluoroquinolones, aminoglycosides, and piperacillin/tazobactam (OXOID). The antibiotic resistance was very high inA. baumanniiwhich were isolated from children in Pakistan specially attending a nephrology unit.

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Barchitta, Martina, Annalisa Quattrocchi, Andrea Maugeri, Maria Clara La Rosa, Claudia La Mastra, Laura Sessa, Pasquale Cananzi, et al. "Antibiotic Consumption and Resistance during a 3-Year Period in Sicily, Southern Italy." International Journal of Environmental Research and Public Health 16, no. 13 (June 26, 2019): 2253. http://dx.doi.org/10.3390/ijerph16132253.

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Antimicrobial resistance (AMR) is one of the biggest issues facing global public health. In 2017, Italy adopted its first National Action Plan on Antimicrobial Resistance 2017–2020, which works through the synergy between national, regional, and local levels. In the framework of a Regional Action Plan on healthcare-associated infections and AMR prevention, the Sicilian Health Authority of the Sicilian Region, Southern Italy, has implemented a surveillance system of antibiotic consumption in hospitals, in the community, and of resistance rates (RRs) in hospital settings. Data on antibiotic consumption and on antibiotic RRs have been collected from 2015 to 2017 from pharmacies and laboratories of participating hospitals and from community, respectively. Data on antibiotic consumption showed that the most consumed antibiotics in hospitals were fluoroquinolones in 2015, penicillin in 2016, and beta-lactams in 2017. From 2015 to 2017, data on Klebsiella pneumoniae showed significant increasing RRs to all antibiotic classes, except to carbapenems. RRs of third-generation cephalosporins and carbapenems Escherichia coli showed significant decreasing trends. RRs of the other microorganisms did not change significantly during the study period. The results from the present study show that in Sicily, the use of antibiotics and RRs for selected microorganisms are at a high level. Immediate strategies are needed to decrease the inappropriate usage of antibiotics and control the spread of AMR.

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Michaud, Gaëlle, Ricardo Visini, Myriam Bergmann, Gianluca Salerno, Rosa Bosco, Emilie Gillon, Barbara Richichi, et al. "Overcoming antibiotic resistance in Pseudomonas aeruginosa biofilms using glycopeptide dendrimers." Chemical Science 7, no. 1 (2016): 166–82. http://dx.doi.org/10.1039/c5sc03635f.

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Zhou, Juyan, Yunhua Chen, Setareh Tabibi, Luis Alba, Elizabeth Garber, and Lisa Saiman. "Antimicrobial Susceptibility and Synergy Studies of Burkholderia cepacia Complex Isolated from Patients with Cystic Fibrosis." Antimicrobial Agents and Chemotherapy 51, no. 3 (December 11, 2006): 1085–88. http://dx.doi.org/10.1128/aac.00954-06.

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ABSTRACT Susceptibility (18 antimicrobial agents including high-dose tobramycin) and checkerboard synergy (23 combinations) studies were performed for 2,621 strains of Burkholderia cepacia complex isolated from 1,257 cystic fibrosis patients. Minocycline, meropenem, and ceftazidime were the most active, inhibiting 38%, 26%, and 23% of strains, respectively. Synergy was rarely noted (range, 1% to 15% of strains per antibiotic combination).

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Auerbach, Tamar, Inbal Mermershtain, Chen Davidovich, Anat Bashan, Matthew Belousoff, Itai Wekselman, Ella Zimmerman, et al. "The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics." Proceedings of the National Academy of Sciences 107, no. 5 (January 11, 2010): 1983–88. http://dx.doi.org/10.1073/pnas.0914100107.

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Crystallographic analysis revealed that the 17-member polyketide antibiotic lankacidin produced by Streptomyces rochei binds at the peptidyl transferase center of the eubacterial large ribosomal subunit. Biochemical and functional studies verified this finding and showed interference with peptide bond formation. Chemical probing indicated that the macrolide lankamycin, a second antibiotic produced by the same species, binds at a neighboring site, at the ribosome exit tunnel. These two antibiotics can bind to the ribosome simultaneously and display synergy in inhibiting bacterial growth. The binding site of lankacidin and lankamycin partially overlap with the binding site of another pair of synergistic antibiotics, the streptogramins. Thus, at least two pairs of structurally dissimilar compounds have been selected in the course of evolution to act synergistically by targeting neighboring sites in the ribosome. These results underscore the importance of the corresponding ribosomal sites for development of clinically relevant synergistic antibiotics and demonstrate the utility of structural analysis for providing new directions for drug discovery.

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Journal articles on the topic 'Antibiotic synergy'

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