ABSTRACT
The consumption of seafood is crucial for food security, but poor hygiene along the food production chain can result in low microbiological quality, posing significant risks for public health and seafood quality. Thus, this study aimed to assess the microbiological quality and antimicrobial sensitivity of E. coli from 69 samples of illegally marketed shrimp and mussels in the Vitória Region, Brazil. These foods exhibited poor microbiological quality due to high counts of mesophilic, psychrotrophic, and enterobacteria microorganisms. While this issue is widespread in this area, shrimp samples displayed higher microbial counts compared to mussels, and fresh mussels had elevated counts of enterobacteria compared to frozen ones. Among the 10 E. coli isolates, none carried the genes blaCTX-M-1, blaCTX-M-2, blaCTX-M-3, blaCTX-M-15, mcr-1, mcr-2, mcr-3, mcr-4, and tet, associated with antibiotic resistance. Phenotypical resistance to tetracycline and fosfomycin was not observed in any isolate, while only 20% demonstrated resistance to ciprofloxacin. Regarding ampicillin and amoxicillin with clavulanic acid, 60% of isolates were resistant, 10% showed intermediate susceptibility, and 30% were sensitive. One isolate was considered simultaneously resistant to ß-lactams and quinolones, and none were conserved as ESBL producers. These findings highlight the inherent risks to local public health that arise from consuming improperly prepared seafood in this area.
ABSTRACT
Bacterial cell wall formation is essential for cellular survival and morphogenesis. The peptidoglycan (PG), a heteropolymer that surrounds the bacterial membrane, is a key component of the cell wall, and its multistep biosynthetic process is an attractive antibacterial development target. Penicillin-binding proteins (PBPs) are responsible for cross-linking PG stem peptides, and their central role in bacterial cell wall synthesis has made them the target of successful antibiotics, including ß-lactams, that have been used worldwide for decades. Following the discovery of penicillin, several other compounds with antibiotic activity have been discovered and, since then, have saved millions of lives. However, since pathogens inevitably become resistant to antibiotics, the search for new active compounds is continuous. The present review highlights the ongoing development of inhibitors acting mainly in the transpeptidase domain of PBPs with potential therapeutic applications for the development of new antibiotic agents. Both the critical aspects of the strategy, design, and structure-activity relationships (SAR) are discussed, covering the main published articles over the last 10 years. Some of the molecules described display activities against main bacterial pathogens and could open avenues toward the development of new, efficient antibacterial drugs.
Subject(s)
Anti-Bacterial Agents , beta-Lactams , Penicillin-Binding Proteins/chemistry , Penicillin-Binding Proteins/metabolism , Anti-Bacterial Agents/pharmacology , beta-Lactams/chemistry , beta-Lactams/pharmacology , Penicillins/chemistry , Penicillins/metabolism , Penicillins/pharmacology , Bacteria/metabolism , Bacterial Proteins/chemistryABSTRACT
Poultry litter is widely used worldwide as an organic fertilizer in agriculture. However, poultry litter may contain high concentrations of antibiotics and/or antimicrobial-resistant bacteria (ARB), which can be mobilized through soil erosion to water bodies, contributing to the spread of antimicrobial resistance genes (ARGs) in the environment. To better comprehend this kind of mobilization, the bacterial communities of four ponds used for irrigation in agricultural and poultry production areas were determined in two periods of the year: at the beginning (low volume of rainfall) and at the end of the rainy season (high volume of rainfall). 16S rRNA gene sequencing revealed not only significantly different bacterial community structures and compositions among the four ponds but also between the samplings. When the DNA obtained from the water samples was PCR amplified using primers for ARGs, those encoding integrases (intI1) and resistance to sulfonamides (sul1 and sul2) and ß-lactams (blaGES, blaTEM and blaSHV) were detected in three ponds. Moreover, bacterial strains were isolated from CHROMagar plates supplemented with sulfamethoxazole, ceftriaxone or ciprofloxacin and identified as belonging to clinically important Enterobacteriaceae. The results presented here indicate a potential risk of spreading ARB through water resources in agricultural areas with extensive fertilization with poultry litter.
ABSTRACT
The aim of this review is to present an update on the susceptibility of viridans group streptococci (VGS) to ß-lactam antimicrobials, with emphasis on the Argentinean scenario. VGS are a heterogeneous group including five groups of species, each one exhibiting peculiar susceptibility patterns to penicillin (PEN). Species of the Streptococcus mitis group are frequently nonsusceptible to PEN. PEN resistance is associated with changes in PEN-binding proteins. In Argentina, one to two thirds of VGS are nonsusceptible to PEN. Third generation cephalosporins and carbapenems are currently more effective in vitro than PEN against VGS. Mortality was associated to nonsusceptibility to PEN in at least two studies involving patients with bacteremia caused by VGS. Treatment of endocarditis due to VGS should be adjusted/to the PEN susceptibility of the isolates. Vancomycin may be an alternative choice for treating endocarditis caused by PEN-resistant isolates (MIC≥4µg/ml).
Subject(s)
Endocarditis , Streptococcal Infections , Humans , Microbial Sensitivity Tests , Streptococcal Infections/drug therapy , Viridans Streptococci , Penicillins , Monobactams , beta-Lactams/pharmacology , beta-Lactams/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Endocarditis/drug therapyABSTRACT
Salmonella enterica causes Salmonellosis, an important infection in humans and other animals. The number of multidrug-resistant (MDR) phenotypes associated with Salmonella spp. isolates is increasing worldwide, causing public health concern. Here, we aim to characterize the antimicrobial-resistant phenotype of 789 non-typhoidal S. enterica strains isolated from human infections in the state of São Paulo, Brazil, along 20 years (2000-2019). Among the non-susceptible isolates, 31.55, 14.06, and 13.18% were resistant to aminoglycosides, tetracycline, and ß-lactams, respectively. Moreover, 68 and 11 isolates were considered MDR and Extended Spectrum ß-Lactamase (ESBL) producers, respectively, whereas one isolate was colistin-resistant. We selected four strains to obtain a draft of the Genome Sequence; one S. Infantis (ST32), one S. Enteritidis (ST11), one S. I 4,[5],12:i:- (ST19), and one S. Typhimurium (ST313). Among them, three presented at least one of the following antimicrobial resistance genes (AMR) linked to mobile DNA: blaTEM-1B, dfrA1, tetA, sul1, floR, aac(6')-laa, and qnrE1. This is the first description of the plasmid-mediated quinolone resistance (PMQR) gene qnrE1 in a clinical isolate of S. I 4,[5],12:i:-. The S. Typhimurium is a colistin-resistant isolate, but did not harbor mcr genes, but it presented mutations within the mgrB, pmrB, and pmrC regions that might be linked to the colistin-resistant phenotype. The virulence pattern of the four isolates resembled the virulence pattern of the highly pathogenic S. Typhimurium UK-1 reference strain in assays involving the in vivo Galleria mellonella model. In conclusion, most isolates studied here are susceptible, but a small percentage present an MDR or ESBL-producer and pathogenic phenotype. Sequence analyses revealed plasmid-encoded AMR genes, such as ß-lactam and fluoroquinolone resistance genes, indicating that these characteristics can be potentially disseminated among other bacterial strains.
Subject(s)
Drug Resistance, Bacterial , Salmonella Infections , Salmonella enterica , Anti-Bacterial Agents/pharmacology , Brazil , Colistin/pharmacology , Drug Resistance, Bacterial/genetics , Drug Resistance, Multiple, Bacterial/genetics , Genetic Background , Humans , Microbial Sensitivity Tests , Salmonella Infections/microbiology , Salmonella enterica/geneticsABSTRACT
Antimicrobial resistance (AMR) remains a major global public health crisis. The food animal industry will face escalating challenges to increase productivity while minimizing AMR, since the global demand for animal protein has been continuously increasing and food animals play a key role in the global food supply, particularly broiler chickens. As chicken products are sources of low-cost, high-quality protein, poultry production is an important economic driver for livelihood and survival in developed and developing regions. The globalization of the food supply, markedly in the poultry industry, is aligned to the globalization of the whole modern society, with an unprecedented exchange of goods and services, and transit of human populations among regions and countries. Considering the increasing threat posed by AMR, human civilization is faced with a complex, multifaceted problem compromising its future. Actions to mitigate antimicrobial resistance are needed in all sectors of the society at the human, animal, and environmental levels. This review discusses the problems associated with antimicrobial resistance in the globalized food chain, using the poultry sector as a model. We cover critical aspects of the emergence and dissemination of antimicrobial resistance in the poultry industry and their implications to public health in a global perspective. Finally, we provide current insights using the multidisciplinary One Health approach to mitigate AMR at the human-animal-environment interface.
Subject(s)
One Health , Poultry , Animals , Anti-Bacterial Agents/pharmacology , Chickens/microbiology , Drug Resistance, Bacterial , Food Chain , Humans , Poultry/microbiologyABSTRACT
Hypersensitivity reactions can be complex and life-threatening to patients, especially when drugs such as ß-lactam antibiotics are involved. To this day, there are diagnostic algorithms and mobile applications that improve the clinical approach, as well as laboratory tests and more specialized procedures, such as skin tests and controlled exposure tests; which are useful for identifying the drug involved and for selecting safe and effective therapeutic alternatives. For several years, the desensitization procedure has been positioned as a vital tool for clinical allergists and for their patients, and it is key to improving clinical outcomes such as survival and quality of life.
Las reacciones de hipersensibilidad pueden ser complejas y poner en peligro la vida de los pacientes, más cuando se involucran medicamentos como los antibióticos betalactámicos. A la fecha, se dispone de algoritmos diagnósticos y aplicaciones móviles que facilitan el abordaje clínico, así como pruebas de laboratorio y procedimientos más especializados, como las pruebas cutáneas y de exposición controlada, útiles para la identificación de la sustancia implicada y para la selección de alternativas terapéuticas seguras y efectivas. Desde hace varios años, el procedimiento de desensibilización se ha posicionado como una herramienta vital para el alergólogo clínico y los pacientes, y es clave para mejorar los desenlaces clínicos, tanto la supervivencia como la calidad de vida.
Subject(s)
Drug Hypersensitivity , Quality of Life , Algorithms , Anti-Bacterial Agents/adverse effects , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/etiology , Drug Hypersensitivity/therapy , Humans , Skin Tests , beta-Lactams/adverse effectsABSTRACT
Streptococcus pneumoniae is an important causal agent of pneumonia, meningitis, sepsis, bacteremia, and otitis media. Penicillin resistance rates in S. pneumoniae have remained stable in Argentina in the last years. In the late '90s more isolates with MIC of penicillin ≥2µg/ml were observed; however, their frequency has decreased in recent years. The phenotypic expression of penicillin resistance is due to a modification in penicillin-binding proteins associated with a mosaic structure in the coding genes. The expansion of successful resistant clones varies among the different regions and is influenced by the use of antibiotics, vaccines, particularly conjugated ones, as well as population density. Parenteral treatment with high doses of penicillin G continues to be effective for the treatment of pneumonia and bacteremia, oral aminopenicillins for otitis media and sinusitis and third generation cephalosporins for meningitis.
Subject(s)
Pneumococcal Infections , Streptococcus pneumoniae , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Argentina , Humans , Microbial Sensitivity Tests , Penicillin Resistance , Pneumococcal Infections/drug therapy , Streptococcus pneumoniae/genetics , beta-Lactams/pharmacologyABSTRACT
Background: Worldwide, chicken meat is widely consumed due to its low cost, high nutritional value and non-interference with religious or cultural beliefs. However, during animal husbandry chickens are exposed to many chemical substances, including tetracyclines and ß-lactams, which are used to prevent and cure several infections. Some residues of these compounds may bioaccumulate and be present in chicken meat after slaughtering, promoting oxidative reactions. Methods: In order to evaluate in vitro carbonylation induced by tetracyclines and ß-lactams residues, a proteomic approach was used. For this, chicken muscle was individually contaminated with tetracyclines (tetracycline, chlortetracycline, oxytetracycline, and doxycycline) and ß-lactams (ampicillin, benzathine penicillin, dicloxacillin and oxacillin) at 0.5, 1.0 and 1.5 times their maximum residue level (MRL). Then, sarcoplasmic, myofibrillar and insoluble proteins were extracted and their content were measured using the Bradford method. Protein carbonylation was measured using the 2,4-Dinitrophenylhydrazine alkaline method. Results: Residues of tetracyclines and ß-lactams induced in vitro carbonylation on sarcoplasmic, myofibrillar and insoluble proteins even at 0.5MRL concentrations ( p<0.05). When comparing the carbonylation induced by both antibiotics no differences were found ( p>0.05). Variables such as the partition coefficient (log P) and the concentration of these antibiotics showed a high correlation with the oxidative capacity of tetracyclines and ß-lactams on chicken breast proteins. Conclusions: This study shows that the presence of tetracyclines and ß-lactams residues at MRLs concentrations promotes in vitro carbonylation on chicken breast proteins. Our results provide important insights about the impact of antibiotics on the integrity of meat proteins intended for human consumption.
Subject(s)
Drug Residues , Tetracyclines , Animals , Anti-Bacterial Agents/pharmacology , Chickens , Drug Residues/analysis , Food Contamination/analysis , Meat/analysis , Proteomics , Tetracyclines/pharmacology , beta-Lactams/analysisABSTRACT
INTRODUCTION: The production of ß-lactamases by Gram-negative bacteria is among the most important factors of resistance to antibiotics, which has contributed to therapeutic failures that currently threaten human and veterinary medicine worldwide. Antimicrobial photodynamic therapy and antimicrobial blue light have a broad-spectrum antibacterial activity against multidrug-resistant and hypervirulent pathogens. OBJECTIVE: To investigate the ability of antimicrobial blue light to inhibit the hydrolytic activity of clinically relevant ß-lactamase enzymes (i.e., KPC, IMP, OXA, CTX-M, and SHV), with further comparison of the inhibitory effects of antimicrobial blue light with methylene blue-mediated antimicrobial photodynamic therapy. METHODS: Blue LED light (λ = 410 ± 10 nm) alone or red LED light (λ = 660 ± 10 nm) in combination with methylene blue were used to inactivate, in vitro, suspensions of Klebsiella pneumoniae strains producing clinically important ß-lactamase enzymes assigned to the A, B and D Ambler molecular classes. Furthermore, ß-lactamase activity inhibition mediated by antimicrobial blue light and methylene blue-mediated antimicrobial photodynamic therapy was measured by using the chromogenic ß-lactam substrate nitrocefin. RESULTS: ß-lactamase activities were effectively inactivated by both visible light-based approaches. In this regard, antimicrobial blue light and methylene blue-antimicrobial photodynamic therapy led to a significant reduction in the hydrolysis of nitrocefin (81-98 %). CONCLUSION: Sublethal doses of antimicrobial blue light and methylene blue-mediated antimicrobial photodynamic therapy are equally effective to inhibit clinically significant ß-lactamases, including extended-spectrum ß-lactamases and carbapenemases.
Subject(s)
Photochemotherapy , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins , Humans , Light , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , beta-LactamasesABSTRACT
Aminoglycosides and ß-lactams are the most commonly used antimicrobial agents in clinical practice. This occurs because they are capable of acting in the treatment of acute bacterial infections. However, the effectiveness of antibiotics has been constantly threatened due to bacterial pathogens producing resistance enzymes. Among them, the aminoglycoside-modifying enzymes (AMEs) and ß-lactamase enzymes are the most frequently reported resistance mechanisms. AMEs can inactivate aminoglycosides by adding specific chemical molecules in the compound, whereas ß-lactamases hydrolyze the ß-lactams ring, preventing drug-target interaction. Thus, these enzymes provide a scenario of multidrug-resistance and a significant threat to public health at a global level. In response to this challenge, in recent decades, several studies have focused on the development of inhibitors that can restore aminoglycosides and ß-lactams activity. In this context, peptides appear as a promising approach in the field of inhibitors for future antibacterial therapies, as multiresistant bacteria may be susceptible to these molecules. Therefore, this review focused on the most recent findings related to peptide-based inhibitors that act on AMEs and ß-lactamases, and how these molecules could be used for future treatment strategies.
Subject(s)
Antimicrobial Cationic Peptides/therapeutic use , Bacterial Infections/drug therapy , Clavulanic Acid/therapeutic use , Drug Resistance, Multiple, Bacterial/drug effects , Sulbactam/therapeutic use , Tazobactam/therapeutic use , Aminoglycosides/metabolism , Aminoglycosides/therapeutic use , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/microbiology , Bacterial Infections/pathology , Drug Design , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/enzymology , Gram-Negative Bacteria/growth & development , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/enzymology , Gram-Positive Bacteria/growth & development , Humans , Kanamycin Kinase/antagonists & inhibitors , Kanamycin Kinase/chemistry , Kanamycin Kinase/metabolism , Nucleotidyltransferases/antagonists & inhibitors , Nucleotidyltransferases/chemistry , Nucleotidyltransferases/metabolism , beta-Lactamases/chemistry , beta-Lactamases/metabolism , beta-Lactams/metabolism , beta-Lactams/therapeutic useABSTRACT
A serious emerging problem worldwide is increased antimicrobial resistance. Acquisition of coding genes for evasion methods of antimicrobial drug mechanisms characterizes acquired resistance. This phenomenon has been observed in Enterobacteriaceae family. Treatment for bacterial infections is performed with antibiotics, of which the most used are beta-lactams. The aim of this study was to correlate antimicrobial resistance profiles in Enterobacteriaceae by phenotypic methods and molecular identification of 14 beta-lactamase coding genes. In this study, 70 exclusive isolates from Brazil were used, half of which were collected in veterinary clinics or hospitals Phenotypic methodologies were used and real-time PCR was the molecular methodology used, through the Sybr Green system. Regargding the results found in the tests it was observed that 74.28% were resistant to ampicillin, 62.85% were resistant to amoxicillin associated with clavalunate. The mechanism of resistance that presented the highest expression was ESBL (17.14%). The genes studied that were detected in a greater number of species were blaGIM and blaSIM (66.66% of the samples) and the one that was amplified in a smaller number of samples was blaVIM (16.66%). Therefore, high and worrying levels of antimicrobial resistance have been found in enterobacteria, and a way to minimize the accelerated emergence of their resistance includes developing or improving techniques that generate diagnoses with high efficiency and speed.
ABSTRACT
Resistance to antibiotics is one of the most relevant public health concerns in the world. Aquatic environments play an important role because they are reservoirs for antibiotic resistance genes and antibiotic-resistant strains, contributing to the spread of resistance. The present study investigated the resistome in Lake Bolonha (three sampling sites) in the Amazon region using a metagenomics approach and culture-dependent methods. Whole-metagenome-based results showed that the most abundant phyla were Protobacteria, Actinobacteria, Firmicutes, Bacteroidetes and Cyanobacteria. The composition of the resistome demonstrated that the genes that confer resistance to ß-lactams were prevalent at all sampling sites, followed by genes conferring resistance to aminoglycosides and tetracycline. Acquired genes encoding extended-spectrum ß-lactamases (e.g., bla CTX-M) and resistance to carbapenems (e.g., bla IMP and bla VIM) were detected through metagenome analysis. Bacteria were isolated from culture medium supplemented with cefotaxime or imipenem, and isolates were identified and analyzed for their antibiotic susceptibility profiles and resistance genes. In total, 98 bacterial isolates belonging to the genera Pseudomonas (37), Acinetobacter (32), Klebsiella (13), Enterobacter (9), Pantoe (3), Stenotrophomonas (3), and Methylobacterium (1) were obtained. Among isolates, the most abundant genes were bla CTX-M (28.3%), bla SHV (22.6%) and bla TEM (18.8%) in isolates from cefotaxime-supplemented medium and bla VIM (28.8%) and bla IMP (22.2%) in isolates recovered from imipenem-supplemented medium. The genes intl1 and intl2 were detected in 19.3% and 7.1% of isolates. Antibiograms showed that 94.9% (from cefotaxime-supplemented medium) and 85.7% (from imipenem-supplemented medium) of the isolates were multidrug resistant. Besides cefotaxime and imipenem, isolates were mostly resistant to aztreonam (91.8%), amoxicillin (98.8%), ampicillin (82.6%), and nalidixic acid (77.5%). Hence, the present study demonstrates that Lake Bolonha is a reservoir of bacteria resistant to antibiotics and resistance genes, some of which are of critical importance to human health.
ABSTRACT
Enterococci are intrinsically resistant to several antimicrobial classes and show a great ability to acquire new mechanisms of resistance. Resistance to ß-lactam antibiotics is a major concern because these drugs either alone or in combination are commonly used for the treatment of enterococcal infections. Ampicillin resistance, which is rare in Enterococcus faecalis, occurs in most of the hospital-associated Enterococcus faecium isolates. High-level resistance to ampicillin in E. faecium is mainly due to the enhanced production of PBP5 and/or by polymorphisms in the beta subunit of this protein. The dissemination of high-level ampicillin resistance can be the result of both clonal spread of strains with mutated pbp5 genes and horizontal gene transfer.
Subject(s)
Enterococcus/drug effects , beta-Lactams/pharmacology , Drug Resistance, Bacterial , Gram-Positive Bacterial Infections/drug therapy , Humans , Lactobacillales , Microbial Sensitivity Tests , beta-Lactams/therapeutic useABSTRACT
OBJECTIVES: The aim of this study was to identify the prevalence of genes encoding resistance to three groups of antimicrobial agents in root canal samples from primary infection or post-treatment disease in Mexico. METHODS: A total of 64 subjects requiring root canal treatment because of primary infection or post-treatment disease were enrolled in this cross-sectional analytical study. Root canal samples were obtained and DNA was isolated. Specific primers for six antimicrobial resistance genes (ARGs) and seven bacterial taxa (five genera and two species) were used. Student's t-test, χ2 test and Fisher's exact test were applied where appropriate to detect statistical differences. RESULTS: The blaTEM-1, ermC and tetM genes were found more frequently in the post-treatment disease group compared with the primary infection group. The occurrence of assessed bacteria was similar in both groups, except for Enterococcus spp. and Porphyromonas endodontalis, which were found at a significantly higher frequency in the post-treatment disease group. It was observed that the post-treatment disease group harboured more ARGs. The most frequent ARG was tetW, whereas tetQ and cfxA were not detected in any case. With respect to bacterial taxa, Fusobacterium spp. was present in 100% of samples, whereas Porphyromonas gingivalis was not observed in any of the samples. CONCLUSIONS: At least one ARG was detected in all cases; moreover, 32.8% of samples were positive for four ARGs, 54.7% for three ARGs, 9.4% for two ARGs and only 3.1% for one ARG. This indicates a high prevalence and diversity of ARGs in these root canal samples.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/genetics , Bacterial Proteins/genetics , Drug Resistance, Bacterial , Methyltransferases/genetics , Tooth Diseases/microbiology , Trans-Activators/genetics , beta-Lactamases/genetics , Adult , Aged , Bacteria/drug effects , Bacteria/isolation & purification , Bacteria/metabolism , Bacterial Proteins/metabolism , Cross-Sectional Studies , Dental Pulp Cavity/microbiology , Female , Humans , Male , Methyltransferases/metabolism , Mexico , Middle Aged , Trans-Activators/metabolism , Young Adult , beta-Lactamases/metabolismABSTRACT
Group A (GAS), B (GBS), C (GCS) and G (GGS) ß-hemolytic streptococci are important human pathogens. They cause infections of different severity and frequency. Nowadays, after 70 years of use, penicillin is still universally active against GAS, GCS and GGS. However, therapeutic failures have been recorded in 2-28% of pharyngitis cases (median: 12%) attributable to different causes. By contrast, some GBS with reduced susceptibility to penicillin have been described, especially in Japan. In this group of bacteria, it is important to highlight that confirmation by reference methods is mandatory when decreased susceptibility to penicillin is suspected as well as checked for the detection of the mechanisms involved.
Subject(s)
Streptococcus/drug effects , beta-Lactams/pharmacology , Drug Resistance, Bacterial , Humans , Microbial Sensitivity TestsABSTRACT
Klebsiella pneumoniae is an important opportunistic pathogen that commonly causes nosocomial infections and contributes to substantial morbidity and mortality. We sought to investigate the antibiotic resistance profile, pathogenic potential and the clonal relationships between K. pneumoniae (n = 25) isolated from patients and sources at a tertiary care hospital's intensive care units (ICUs) in the northern region of Brazil. Most of K. pneumoniae isolates (n = 21, 84%) were classified as multidrug resistant (MDR) with high-level resistance to ß-lactams, aminoglycosides, quinolones, tigecycline, and colistin. All the 25 isolates presented extended-spectrum beta-lactamase-producing (ESBL), including carbapenemase producers, and carried the bla KPC (100%), bla TEM (100%), bla SHV variants (n = 24, 96%), bla OXA-1 group (n = 21, 84%) and bla CTX-M-1 group (n = 18, 72%) genes. The K2 serotype was found in 4% (n = 1) of the isolates, and the K1 was not detected. The virulence-associated genes found among the 25 isolates were mrkD (n = 24, 96%), fimH-1 (n = 22, 88%), entB (100%), iutA (n = 10, 40%), ybtS (n = 15, 60%). The genes related with efflux pumps and outer membrane porins found were AcrAB (100%), tolC (n = 24, 96%), mdtK (n = 22, 88%), OmpK35 (n = 15, 60%), and OmpK36 (n = 7, 28%). ERIC-PCR was employed to determine the clonal relationship between the different isolated strains. The obtained ERIC-PCR patterns revealed that the similarity between isolates was above 70%. To determine the sequence types (STs) a multilocus sequence typing (MLST) assay was used. The results indicated the presence of high-risk international clones among the isolates. In our study, the wide variety of MDR K. pneumoniae harboring ß-lactams and virulence genes strongly suggest a necessity for the implementation of effective strategies to prevent and control the spread of antibiotic resistant infections.
ABSTRACT
Bacterial resistance has become a problem of great concern all over the world. Gram-negative bacteria, including the Enterobacteriaceae family and Pseudomonas and Acinetobacter species, are among the leading causes of healthcare-associated infections. The rate of antibiotic resistance among these pathogens has increased dramatically in recent years, reaching a pandemic scale. The most common mechanism of resistance described for Gram-negative bacteria consists of beta-lactamase production. These enzymes hydrolyze beta-lactam antibiotics, which are among the most commonly used antimicrobial agents. As with other antibiotics, reports of bacterial resistance to these agents have increased in recent years. An alternative method for combating beta-lactamasemediated resistance has been the use of small beta-lactamase inhibitors (e.g., clavulanic acid and tazobactam), allowing the resurgence of beta-lactam antibiotics for the treatment of infections caused by beta-lactamase-producing bacteria. However, due to the beta-lactamase group's diversity, some of them present resistance to conventional beta-lactamase inhibitors. Bearing this in mind, in the last two decades, beta- lactamase inhibitor peptides have been developed as alternative adjuvants to strike back against such strains. In this review, we outline the most recent findings related to the design of beta-lactamase inhibitor peptides and their biotechnological potential.
Subject(s)
Bacterial Infections/drug therapy , Drug Resistance, Bacterial , Peptides/pharmacology , beta-Lactamase Inhibitors/pharmacology , Humans , beta-LactamasesSubject(s)
Alphaproteobacteria/genetics , Bacterial Proteins/genetics , Chromosomes/genetics , beta-Lactam Resistance/genetics , beta-Lactamases/genetics , Alphaproteobacteria/enzymology , Alphaproteobacteria/isolation & purification , Bacterial Proteins/isolation & purification , Humans , Microbial Sensitivity Tests/methods , beta-Lactamases/isolation & purificationABSTRACT
The objective of this study was to evaluate the microbial susceptibility to ß-lactams and metronidazole, and evaluate the production of ß-lactamases by microorganisms isolated from patients with chronic or aggressive periodontitis. The samples were obtained from 50 patients with periodontitis and microorganisms were isolated onto selective and nonselective culture media, identified by biochemical methods and tested for susceptibility to antimicrobial agents (amoxicillin, amoxicillin/clavulanate, cefoxitin, imipenem, metronidazole, penicillin G). The isolates were resistant to at least 1 mg/ml of any drug tested were evaluated to verify the production of ß-lactamases by the method of double layer (or biological) and chromogenic cephalosporin using nitrocefin. The results evidenced resistance to amoxicillin and penicillin G, while the susceptibility to association amoxicillin/clavulanate, imipenem and cefoxitin was widely disseminated among the organisms. Resistance to these drugs showed a clear correlation with the production of ß-lactamase in the majority of microbial groups.
El objetivo fue evaluar la susceptibilidad a ß-lactámicos y metronidazol, y evaluar la producción de ß-lactamasas por microorganismos aislados de pacientes con periodontitis crónica y agresivo. Las muestras fueron obtenido de 50 pacientes con periodontitis y microorganismos aislados en medios de cultivo selectivos y no selectivos, identificados por métodos bioquímicos y probados a la susceptibilidad a los antimicrobianos (amoxicilina, amoxicilina/clavulanato, cefoxitina, imipenem, metronidazol, penicilina G). Los aislados fueron resistentes a por lo menos 1 mg/ml de cualquier drogas analizadas fueron evaluados para verificar la producción de ß-lactamasas por el método de doble capa (o biológico) y nitrocefina. Los resultados mostraron resistencia a amoxicilina y penicilina G, mientras la susceptibilidad a la asociación amoxicilina/ clavulanate, cefoxitina y imipenem fue ampliamente difundido entre los microrganismos. Resistencia a estas drogas mostraron una clara correlación con la producción de ß-lactamasas en la mayoría de grupos microbianos.