Antimicrobial-ResistantEscherichia coliin Public Beach Waters in Quebec

INTRODUCTION: Human exposure to antimicrobial-resistant bacteria may result in the transfer of resistance to commensal or pathogenic microbes present in the gastrointestinal tract, which may lead to severe health consequences and difficulties in treatment of future bacterial infections. It was hypothesized that the recreational waters from beaches represent a source of antimicrobial-resistantEscherichia colifor people engaging in water activities.OBJECTIVE: To describe the occurrence of antimicrobial-resistantE coliin the recreational waters of beaches in southern Quebec.METHODS: Sampling occurred over two summers; in 2004, 674 water samples were taken from 201 beaches, and in 2005, 628 water samples were taken from 177 beaches. The minimum inhibitory concentrations of the antimicrobial-resistantE coliisolates against a panel of 16 antimicrobials were determined using microbroth dilution.RESULTS: For 2004 and 2005, respectively, 28% and 38% of beaches sampled had at least one water sample contaminated byE coliresistant to one or more antimicrobials, and more than 10% of the resistant isolates were resistant to at least one antimicrobial of clinical importance for human medicine. The three antimicrobials with the highest frequency of resistance were tetracycline, ampicillin and sulfamethoxazole.DISCUSSION: The recreational waters of these beaches represent a potential source of antimicrobial-resistant bacteria for people engaging in water activities. Investigations relating the significance of these findings to public health should be pursued.

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Antibacterial Activity of Defatted and Nondefatted Methanolic Extracts of Aframomum melegueta K. Schum. against Multidrug-Resistant Bacteria of Clinical Importance

The Scientific World JOURNAL ◽

10.1155/2020/4808432 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Olufunmiso Olusola Olajuyigbe ◽

Otunola Adedayo ◽

Roger Murugas Coopoosamy

Keyword(s):

Antibacterial Activity ◽

Bacterial Infections ◽

Methanol Extract ◽

Clinical Importance ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Plant Materials ◽

Methanolic Extracts ◽

Agar Dilution ◽

Inhibition Zones

The antibacterial activity of the extracts of Aframomum melegueta including n-hexane extract (NHE), nondefatted methanol extract (NDME), and defatted methanol extract (DME) was investigated in this study. The NHE exhibited no antibacterial activity. The DME showed higher antibacterial activity than the NDME against the different isolates. At the highest concentration of 10 mg/mL in agar diffusion, NDME produced inhibition zones ranging from 11 to 29 mm against the microorganisms while DME produced inhibition zones ranging from 20 to 40 mm with the concentration of 10 mg/mL against the microorganisms. 0.1 mg/mL of the DME produced inhibition zones ranging between 12 and 14 mm in Aeromonas hydrophila ATCC 35654 and Pseudomonas aeruginosa ATCC 15442, respectively, while none of the isolates were inhibited by the NDME at a concentration of 1 mg/mL or less. In the agar dilution assay, the MICs of the NDME and DME ranged between 0.31 and 10 mg/mL, but more isolates were inhibited at 0.31 mg/mL of DME than those in NDME. In macrobroth assay, the MICs of the NDME ranged between 0.15 and 5.0 mg/mL and the MBCs ranged between 0.63 and 5.0 mg/mL, and the MICs of the DME ranged between 0.08 and 5.0 mg/mL and the MBCs were between 0.31 and 5.0 mg/mL. This study indicated that DME was more active with higher antibacterial activity than the NDME of this plant, and extracting the fatty portion of plant materials prior susceptibility testing would allow plant extracts to be more effective as well as justifying the use of Aframomum melegueta in traditional medicine for the treatment of bacterial infections.

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Comparative stability and growth requirements of S. aureus and faecal indicator bacteria in seawater

Water Science & Technology ◽

10.2166/wst.2006.465 ◽

2006 ◽

Vol 54 (3) ◽

pp. 169-175 ◽

Cited By ~ 8

Author(s):

R.S. Fujioka ◽

T.M. Unutoa

Keyword(s):

Environmental Conditions ◽

Water Samples ◽

High Salinity ◽

Indicator Bacteria ◽

Nutritional Requirements ◽

Recreational Waters ◽

E Coli ◽

Growth Requirements ◽

Comparative Stability ◽

Bactericidal Agent

The fate (stability, multiplication) of S. aureus, E. coli and E. faecalis was determined in three classes of recreational waters (seawater, estuarine, stream) supplemented with nutrients in the form of sewage and peptone. In the absence of sunlight (24±2 °C), all bacteria in all water samples did not multiply and were slowly (days) inactivated. When 50% sewage was added to all water samples, E. coli and E. faecalis multiplied but S. aureus did not. When peptone (0.05%, 0.5%) was the added nutrient, the three bacteria multiplied. In the presence of sunlight (15–27 °C), S. aureus was inactivated rapidly (hours) in all water samples. These results show that when their nutritional requirements are met, S. aureus, E. coli and E. faecalis can multiply in the high salinity conditions of seawater. However, under environmental conditions, sunlight is an effective natural bactericidal agent.

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Post-antibiotic era in hemodialysis? Two case reports of simultaneous colonization and bacteremia by multidrug-resistant bacteria

Brazilian Journal of Nephrology ◽

10.1590/2175-8239-jbn-2020-0070 ◽

2020 ◽

Author(s):

Johanna M. Vanegas ◽

Lorena Salazar-Ospina ◽

Gustavo A. Roncancio ◽

Julián Builes ◽

Judy Natalia Jiménez

Keyword(s):

Pseudomonas Aeruginosa ◽

Bacterial Infections ◽

Case Reports ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Control Measures ◽

Resistant Bacteria ◽

Multidrug Resistant Bacteria ◽

E Coli ◽

Carbapenem Resistant

ABSTRACT The emergence of resistance mechanisms not only limits the therapeutic options for common bacterial infections but also worsens the prognosis in patients who have conditions that increase the risk of bacterial infections. Thus, the effectiveness of important medical advances that seek to improve the quality of life of patients with chronic diseases is threatened. We report the simultaneous colonization and bacteremia by multidrug-resistant bacteria in two hemodialysis patients. The first patient was colonized by carbapenem- and colistin-resistant Klebsiella pneumoniae, carbapenem-resistant Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA). The patient had a bacteremia by MRSA, and molecular typing methods confirmed the colonizing isolate was the same strain that caused infection. The second case is of a patient colonized by extended-spectrum beta-lactamases (ESBL)-producing Escherichia coli and carbapenem-resistant Pseudomonas aeruginosa. During the follow-up period, the patient presented three episodes of bacteremia, one of these caused by ESBL-producing E. coli. Molecular methods confirmed colonization by the same clone of ESBL-producing E. coli at two time points, but with a different genetic pattern to the strain isolated from the blood culture. Colonization by multidrug-resistant bacteria allows not only the spread of these microorganisms, but also increases the subsequent risk of infections with limited treatments options. In addition to infection control measures, it is important to establish policies for the prudent use of antibiotics in dialysis units.

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Drug Resistance of Pathogens Causing Nosocomial Infection in Orthopedics from 2012 to 2017: A 6-Year Retrospective Study

10.21203/rs.3.rs-103706/v1 ◽

2020 ◽

Author(s):

Xiaowei Yang ◽

Runsheng Guo ◽

Banglin Xie ◽

Qi Lai ◽

Jiaxiang Xu ◽

...

Keyword(s):

Drug Resistance ◽

Retrospective Study ◽

Antimicrobial Resistance ◽

Bacterial Infections ◽

Multidrug Resistant ◽

Dynamic Monitoring ◽

Resistant Bacteria ◽

Clinical Microbiology Laboratory ◽

Valuable Insight ◽

E Coli

Abstract Background: Hospital-acquired infections (HAIs) are an emerging global problem that increases in-hospital mortality, length of stay, and cost. We performed a 6-year retrospective study to provide valuable insight into appropriate antibiotic use in HAI cases. We also aimed to understand how hospitals could reduce pathogen drug resistance in a population that overuses antibiotics.Methods: All data (2012–2017) were obtained from the Hospital Information Warehouse and Clinical Microbiology Laboratory.Results: We isolated 1392 pathogen strains from patients admitted to the orthopedics department during 2012–2017. Escherichia coli (14.7%, 204/1392), Enterobacter cloacae (13.9%, 193/1392), and Staphylococcus aureus (11.3%, 157/1392) were the most common pathogens causing nosocomial infections. The dominant Gram-negative bacterium was E. coli, with high resistance to ampicillin, levofloxacin, cotrimoxazole, gentamicin, and ciprofloxacin, in that order. E. coli was least resistant to amikacin, cefoperazone-sulbactam. The most dominant Gram-positive bacterium was S. aureus, highly resistant to penicillin and ampicillin, but not resistant to fluoroquinolones and cotrimoxazole. Analysis of risk factors related to multidrug-resistant bacteria showed that patients with open fractures were significantly more susceptible to methicillin-resistant S. aureus infections (p < 0.05). Additionally, extended-spectrum β-lactamase-producing E. coli infections occurred significantly more often in patients with degenerative diseases (p < 0.05). Elderly patients tended to be more susceptible to multidrug-resistant bacterial infections, but this outcome was not statistically significant.Conclusions:Antimicrobial resistance is a serious problem in orthopedics. To effectively control antimicrobial resistance among pathogens, we advocate extensive and dynamic monitoring of MDR bacteria, coupled with careful use of antibiotics.

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Mode of action of the 2-phenylquinoline efflux inhibitor PQQ4R againstEscherichia coli

PeerJ ◽

10.7717/peerj.3168 ◽

2017 ◽

Vol 5 ◽

pp. e3168 ◽

Cited By ~ 14

Author(s):

Diana Machado ◽

Laura Fernandes ◽

Sofia S. Costa ◽

Rolando Cannalire ◽

Giuseppe Manfroni ◽

...

Keyword(s):

Mode Of Action ◽

Bacterial Infections ◽

Efflux Pump ◽

Resistant Bacteria ◽

Gram Negative Bacteria ◽

Synergistic Activity ◽

Dependent Manner ◽

Gram Negative ◽

E Coli ◽

Efflux Pump Inhibitors

Efflux pump inhibitors are of great interest since their use as adjuvants of bacterial chemotherapy can increase the intracellular concentrations of the antibiotics and assist in the battle against the rising of antibiotic-resistant bacteria. In this work, we have described the mode of action of the 2-phenylquinoline efflux inhibitor (4-(2-(piperazin-1-yl)ethoxy)-2-(4-propoxyphenyl) quinolone – PQQ4R), againstEscherichia coli,by studding its efflux inhibitory ability, its synergistic activity in combination with antibiotics, and compared its effects with the inhibitors phenyl-arginine-β-naphthylamide (PAβN) and chlorpromazine (CPZ). The results showed that PQQ4R acts synergistically, in a concentration dependent manner, with antibiotics known to be subject to efflux inE. colireducing their MIC in correlation with the inhibition of their efflux. Real-time fluorometry assays demonstrated that PQQ4R at sub-inhibitory concentrations promote the intracellular accumulation of ethidium bromide inhibiting its efflux similarly to PAβN or CPZ, well-known and described efflux pump inhibitors for Gram-negative bacteria and whose clinical usage is limited by their levels of toxicity at clinical and bacteriological effective concentrations. The time-kill studies showed that PQQ4R, at bactericidal concentrations, has a rapid antimicrobial activity associated with a fast decrease of the intracellular ATP levels. The results also indicated that the mode of action of PQQ4R involves the destabilization of theE. coliinner membrane potential and ATP production impairment, ultimately leading to efflux pump inhibition by interference with the energy required by the efflux systems. At bactericidal concentrations, membrane permeabilization increases and finally ATP is totally depleted leading to cell death. Since drug resistance mediated by the activity of efflux pumps depends largely on the proton motive force (PMF), dissipaters of PMF such as PQQ4R, can be regarded as future adjuvants of conventional therapy againstE. coliand other Gram-negative bacteria, especially their multidrug resistant forms. Their major limitation is the high toxicity for human cells at the concentrations needed to be effective against bacteria. Their future molecular optimization to improve the efflux inhibitory properties and reduce relative toxicity will optimize their potential for clinical usage against multi-drug resistant bacterial infections due to efflux.

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Design, Overproduction and Purification of the Chimeric Phage Lysin MLTphg Fighting against Staphylococcus aureus

Processes ◽

10.3390/pr8121587 ◽

2020 ◽

Vol 8 (12) ◽

pp. 1587

Author(s):

Feng Wang ◽

Xiaohang Liu ◽

Zhengyu Deng ◽

Yao Zhang ◽

Xinyu Ji ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Bacterial Infections ◽

Antimicrobial Agents ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Antibiotic Resistant ◽

E Coli ◽

Conventional Antibiotics ◽

Phage Lysin ◽

Shed Light

With the increasing spread of multidrug-resistant bacterial pathogens, it is of great importance to develop alternatives to conventional antibiotics. Here, we report the generation of a chimeric phage lysin, MLTphg, which was assembled by joining the lysins derived from Meiothermus bacteriophage MMP7 and Thermus bacteriophage TSP4 with a flexible linker via chimeolysin engineering. As a potential antimicrobial agent, MLTphg can be obtained by overproduction in Escherichia coli BL21(DE3) cells and the following Ni-affinity chromatography. Finally, we recovered about 40 ± 1.9 mg of MLTphg from 1 L of the host E. coli BL21(DE3) culture. The purified MLTphg showed peak activity against Staphylococcus aureus ATCC6538 between 35 and 40 °C, and maintained approximately 44.5 ± 2.1% activity at room temperature (25 °C). Moreover, as a produced chimera, it exhibited considerably improved bactericidal activity against Staphylococcus aureus (2.9 ± 0.1 log10 reduction was observed upon 40 nM MLTphg treatment at 37 °C for 30 min) and also a group of antibiotic-resistant bacteria compared to its parental lysins, TSPphg and MMPphg. In the current age of growing antibiotic resistance, our results provide an engineering basis for developing phage lysins as novel antimicrobial agents and shed light on bacteriophage-based strategies to tackle bacterial infections.

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1004. Cladophora in Lake Michigan May Serve as Important Reservoirs for Antibiotic-Resistant Bacteria

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1198 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S592-S593

Author(s):

Dannielle C Grayer ◽

Latania K Logan

Keyword(s):

Surface Water ◽

Water Samples ◽

Lake Michigan ◽

Primary Objective ◽

Resistant Bacteria ◽

Research Station ◽

Antibiotic Resistant ◽

E Coli ◽

Amoxicillin Clavulanate ◽

Surface Water Samples

Abstract Background Cladophora is a green algae, native to the Great Lakes, and found in large quantities along Lake Michigan shorelines. Previous studies have shown that Cladophora provide protection and nutrients for the Enterobacteriaceae (Ent) family, allowing persistence and regrowth. Chicago waterways harbor concerning antibiotic-resistant (AR) Ent, however the community reservoirs are unknown. Our primary objective was to assess whether Cladophora harbor AR Ent and to secondarily assess AR Ent in local beach waters where Cladophora are present. Figure 1. Map of Lake Michigan showing sites (S1-S3) where Cladophora samples were collected. NB, North Beach, Racine, Wisconsin; Michigan City, Indiana; PL, Portage Lakefront, Indiana Dunes National Park, Indiana. Figure 2. Map of Lake Michigan showing sites (S4-S7) where beach surface water samples were obtained. Montrose, Foster, 63rd St, & Calumet beaches in Chicago, Illinois. Methods Cladophora were processed from three Indiana Lake Michigan sites (S1 and S2; Fig 1) in 2002 and 2012 (S3; Fig 1) at the USGS Lake Michigan Ecological Research Station (Chesterton, IN). In 2015, surface water samples were obtained by the USGS at four Chicago beaches (S4-S7; Fig 2), which also amass Cladophora. Bacteria were isolated shortly after collection. In 2019-2020, Ent were cultivated and susceptibilities were performed at Rush. Results In 2002-2003 (S1 and S2), 160 E. coli were cultured from Cladophora. There was AR to multiple classes, highest overall in tetracyclines (7.5%, range 6.2%-18.7%), cefoxitin (8%), and cefazolin (5.6%). Resistance to cefuroxime was 0.6%. Four Salmonella isolates from 2012 (S3) were pan-susceptible, while two Citrobacter isolates were resistant to penicillins, 1st and 2nd generation cephalosporins, and cephamycins. Beach surface water samples from 2015 revealed more pronounced AR in E. coli (n=185) involving multiple classes, including highest in ampicillin (12.4%), tetracyclines (8.1%); piperacillin (7%); cefazolin (3.8%), cephamycins (3.2%) and amoxicillin-clavulanate (2.7%). Resistance to 3rd-generation cephalosporins, fluoroquinolones, trimethoprim/sulfamethoxazole ranged from 0.5-2%. AR Ent varied by beach site with highest percentages at S4, the only site with an associated dog beach. Conclusion These findings suggest that Cladophora in recreational waterways may serve as reservoirs for AR Ent. Differences in AR Ent at beach sites may reflect varying degrees of fecal contamination. Identifying community reservoirs is key to better understanding the acquisition of antibiotic resistant Ent among healthy populations and has long-term ecological and public health implications. Disclosures All Authors: No reported disclosures

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Exploration of Antimicrobial Potency of Mangrove Symbiont Against Multi-Drug Resistant Bacteria

Jurnal Ilmiah Perikanan dan Kelautan ◽

10.20473/jipk.v13i2.26199 ◽

2021 ◽

Vol 13 (2) ◽

pp. 222

Author(s):

Delianis Pringgenies ◽

Wilis Ari Setyati ◽

Ali Djunaedi ◽

Rini Pramesti ◽

Siti Rudiyanti ◽

...

Keyword(s):

Antimicrobial Properties ◽

Inhibition Zone ◽

Resistant Bacteria ◽

Drug Resistant ◽

E Coli ◽

Drug Resistant Bacteria ◽

Acanthus Ilicifolius ◽

Pathogenic Microbes ◽

Microbial Isolates ◽

Antimicrobial Potency

Highlight ResearchAntimicrobial potential against the test microbesRhizhopora mucronata isolate showed 95% homology with Bacillus subtilis, and 97% homology with Bacillus oceanisediminis,Acanthus ilicifolius isolate showed 96% homology with Paracoccus caeni, and 89% homology with Bacillus circulans. The study found 4 isolates with antimicrobial potency against MDR pathogenic microbes.The symbiont microbes taken from Rhizophora mucronata and Acanthus ilicifolius were determined to be of the genus Bacillus and Paracoccus AbstractAntimicrobial property of mangrove symbiont have the ability to fight Multi Drug Resistant bacteria which were Staphylococcus aureus, Escherichia coli, and Vibrio haryeyi. This study aimed to determine the potential of symbiont microbes from the root of Rhizopora mucronata and Acanthus iilicifolius as antimicrobial agents against multi-drug resistant (MDR) pathogenic microbes. This research was conducted during July to November 2020. The MDR bacteria were S. aureus, E. coli, and V. harveyi MDR test microbes. The symbiont microbes were identified through molecular analyses (PCR 16S rDNA). Isolation of symbiont microbes from R. mucronata resulted in 16 isolates, while isolation from A. iilicifolius resulted in 14 isolates. Based on the antimicrobial qualitative test against S. aureus, 8 out of 16 microbial isolates from R. mucronata were found to show antimicrobial properties. The testing of A. ilicifolius symbiont microbes against S. aureus showed 8 out of 14 isolates with antimicrobial properties. The test against E. coli resulted in 2 out of 16 microbial isolates from R. mucronata and 5 out of 14 isolates from A. ilicifolius with antimicrobial properties. The test against V. harveyi resulted in two out of 16 microbial isolates from R.mucronata and 4 out of 14 isolates from A. ilicifolius with antimicrobial properties. The quantitative test found 2 isolates from R. mucronta, namely isolates RM10 and RM12, with antimicrobial properties against MDR strain E. coli, with the best isolate being RM10, which produced 11.22 mm of inhibition zone diameter. Furthermore, the selection of isolates was based on the size of the inhibition zone, the clearness of the inhibition zone and the potential for antibacterial activity. Based on their overall antimicrobial potential against the test microbes, four isolates were selected. Molecular analyses of RM12 isolate showed 95% homology with Bacillus subtilis, of RM 10 isolate showed 97% homology with Bacillus oceanisediminis, of AC isolate showed 96% homology with Paracoccus caeni, and of AC 5 isolate showed 89% homology with Bacillus circulans. The study found four isolates with antimicrobial potency against MDR pathogenic microbes. The symbiont microbes taken from R. mucronata and A. ilicifolius were determined to be of the genus Bacillus and Paracoccus.

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ESKAPEade in hematological malignancies: Dare to review!

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18110 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18110-e18110

Author(s):

Cesar Giancarlo Gentille Sanchez ◽

Kai Sun ◽

Purnima Sravanti Teegavarapu ◽

Mamta Puppala ◽

Stephen Tc Wong ◽

...

Keyword(s):

Broad Spectrum ◽

Bacterial Infections ◽

Hematological Malignancies ◽

Prophylactic Antibiotic ◽

Resistant Bacteria ◽

Hematological Cancer ◽

E Coli ◽

Broad Spectrum Antibiotics ◽

Hematological Cancers ◽

Severe Infections

e18110 Background: Patients with hematological cancers are at a high risk for increasingly resistant and severe infections. The Infectious Diseases Society of America has defined commonly resistant bacteria as ESKAPE (Enterococcus, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter, Pseudomonas aeruginosa, Enterobacter/Enterobacteriaceae). We performed a retrospective review of the rate of ESKAPE infections, resistance profile, and outcomes in patients with various hematological malignancies at the Houston Methodist Hospital from 2006 to 2015. Methods: The patient data was obtained from METEOR (Methodist Environment for Translational Enhancement and Outcomes Research), a clinical data warehouse that contains records dating back to January 1, 2006 with over 3 million patients and over 10 million unique patient encounters. We queried for leukemia (AML, CML, ALL, CLL), amyloidosis and myelodysplastic syndrome (MDS) along with hospitalizations due to bacterial infections. Baseline demographics and overall outcomes were also obtained. Results: Out of 6017 patients with Hematological Malignancies, 632 patients were found; 322 had MDS, 225 had AML, 136 had CLL, 49 had ALL, 60 had CML, 97 had amyloidosis and 13 had an unspecified hematological cancer. Of 1091 infectious events, 60.5% were ESKAPE infections. The bacteria most frequently isolated were Enterococcus (24.7%), MRSA (19.8%) and Pseudomonas (18.0%). Patients with MDS (41.5%), AML (20.6%) and CLL (14.4%) were mostly affected. A prevalent resistance to levofloxacin was detected in gram positives and gram negatives (29-54%). Pseudomonas, E. coli, Proteus and K. pneumoniae showed a significant resistance to broad spectrum antibiotics including aztreonam (23-34%), cefepime (7-23%) and imipenem (22%). Proteus had the highest mortality rate (45.2%), followed by Enterococcus (44.2%) and Pseudomonas. (36.7%). Conclusions: Hematological cancers with risk for neutropenia such as MDS and AML were the most affected by ESKAPE. A significant resistance to levofloxacin, a prophylactic antibiotic, was seen. Gram negative pathogens had an increased resistance to broad spectrum antibiotics and higher mortality rates. New strategies for reducing ESKAPE in MDS and AML are required.

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Efficacy of OH-CATH30 and Its Analogs against Drug-Resistant BacteriaIn Vitroand in Mouse Models

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.06304-11 ◽

2012 ◽

Vol 56 (6) ◽

pp. 3309-3317 ◽

Cited By ~ 38

Author(s):

Sheng-An Li ◽

Wen-Hui Lee ◽

Yun Zhang

Keyword(s):

Mouse Models ◽

Bacterial Infections ◽

Resistant Bacteria ◽

Infection Model ◽

Drug Resistant ◽

Content Type ◽

E Coli ◽

Drug Resistant Bacteria

ABSTRACTAntimicrobial peptides (AMPs) have been considered alternatives to conventional antibiotics for drug-resistant bacterial infections. However, their comparatively high toxicity toward eukaryotic cells and poor efficacyin vivohamper their clinical application. OH-CATH30, a novel cathelicidin peptide deduced from the king cobra, possesses potent antibacterial activityin vitro. The objective of this study is to evaluate the efficacy of OH-CATH30 and its analog OH-CM6 against drug-resistant bacteriain vitroandin vivo. The MICs of OH-CATH30 and OH-CM6 ranged from 1.56 to 12.5 μg/ml against drug-resistant clinical isolates of several pathogenic species, includingEscherichia coli,Pseudomonas aeruginosa, and methicillin-resistantStaphylococcus aureus. The MICs of OH-CATH30 and OH-CM6 were slightly altered in the presence of 25% human serum. OH-CATH30 and OH-CM6 killedE. coliquickly (within 60 min) by disrupting the bacterial cytoplasmic membrane. Importantly, the 50% lethal doses (LD50) of OH-CATH30 and OH-CM6 in mice following intraperitoneal (i.p.) injection were 120 mg/kg of body weight and 100 mg/kg, respectively, and no death was observed at any dose up to 160 mg/kg following subcutaneous (s.c.) injection. Moreover, 10 mg/kg OH-CATH30 or OH-CM6 significantly decreased the bacterial counts as well as the inflammatory response in a mouse thigh infection model and rescued infected mice in a bacteremia model induced by drug-resistantE. coli. Taken together, our findings demonstrate that the natural cathelicidin peptide OH-CATH30 and its analogs exhibit relatively low toxicity and potent efficacy in mouse models, indicating that they may have therapeutic potential against the systemic infections caused by drug-resistant bacteria.

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