Bacteriophages offer an alternative for the treatment of multidrug-resistant bacterial diseases as their mechanism of action differs from that of antibiotics. However, their application in the clinical field is limited to specific cases of patients with few or no other alternative therapies. This systematic review assesses the effectiveness and safety of phage therapy against multidrug-resistant bacteria through the evaluation of studies published over the past decade. To that end, a bibliographic search was carried out in the PubMed, Science Direct, and Google Scholar databases. Of the 1500 studies found, 27 met the inclusion criteria, with a total of 165 treated patients. Treatment effectiveness, defined as the reduction in or elimination of the bacterial load, was 85%. Except for two patients who died from causes unrelated to phage therapy, no serious adverse events were reported. This shows that phage therapy could be an alternative treatment for patients with infections associated with multidrug-resistant bacteria. However, owing to the phage specificity required for the treatment of various bacterial strains, this therapy must be personalized in terms of bacteriophage type, route of administration, and dosage.

Klebsiella pneumoniae is a bacterial pathogen that has developed resistance to multiple antibiotics and is a major cause of nosocomial infections worldwide. Carbapenemase-producing Klebsiella pneumoniae have been isolated in many hospitals in Venezuela, but they have not been well-studied. The aim of this study was to characterize carbapenem-resistant Klebsiella pneumoniae isolates from the pediatric service of a hospital located in Anzoategui State, in the eastern part of Venezuela. Nineteen Klebsiella pneumoniae strains isolated in the hospital from April to July 2014 were evaluated phenotypically and molecularly for the presence of carbapenemases blaKPC, blaIMP and blaVIM. Molecular epidemiology was performed with Repetitive Extragenic Palindromic-PCR (REP-PCR) and Multilocus Sequence Typing (MLST). They were also studied for phenotypic and molecular resistance to a quaternary ammonium compound (QAC) disinfectant. All 19 isolates contained both bla VIM-2 and bla KPC-2 genes, and the bla KPC-2 gene was associated with Tn4401b. All isolates were phenotypically sensitive to QACs and contained qacΔE and addA2 genes typical of class 1 integrons. Analysis by REP-PCR and MLST showed that all isolates had identical profiles characteristic of sequence type ST833. All 19 strains are bla VIM-2 and bla KPC-2−producing ST833 K. pneumoniae sensitive to QACs. This analysis may help to understand the routes of dissemination and confirms that QAC disinfectants can be used to help control their spread.

The Enterobacter cloacae complex is an emerging opportunistic pathogen whose increased resistance to carbapenems is considered a public health problem. This is due to the loss of efficacy of beta-lactam antibiotics, which are used as the first treatment option in the management of infections caused by Gram-negative bacteria. The objective of this study was to perform the molecular characterization of 28 isolates of the E. cloacae complex resistant to cephalosporins and carbapenems isolated between 2011 and 2018 from five hospitals located in the municipality of Santiago de Cali, Colombia. Molecular detection of bla_KPC, bla_VIM, bla_NDM and bla_OXA-48-like genes was performed on these isolates and the genetic relationship between the isolates was assessed using multilocus sequence typing (MLST). Forty-three percent of the isolates carried the bla_KPC-2 gene variant. MLST showed high genetic diversity among isolates, the most frequent being the sequence type ST510 with a frequency of 50%. The identification of the genes involved in carbapenem resistance and dispersing genotypes is an important step toward the development of effective prevention and epidemiological surveillance strategies in Colombian hospitals.

Fluoroquinolones (FQs) are antibiotics useful in the treatment of drug-resistant tuberculosis, but FQ-resistant mutants can be selected rapidly. Although mutations in the DNA gyrase are the principal cause of this resistance, pentapeptide proteins have been found to confer low-level FQ resistance in Gram-negative bacteria. MfpA is a pentapeptide repeat protein conserved in mycobacterial chromosomes, where it is adjacent to a group of four highly conserved genes termed a conservon. We wished to characterize the transcriptional regulation of the mfpA gene and relate its expression to ciprofloxacin resistance in M. smegmatis. Reverse transcription PCR showed that mfpA gene is part of an operon containing the conservon genes. Using a transcriptional fusion, we showed that a promoter was located 5 to the mfpEA operon. We determined the promoter activity under different growth conditions and found that the expression of the operon increases slightly in late growth phases in basic pH and in subinhibitory concentrations of ciprofloxacin. Finally, by cloning the mfpA gene in an inducible vector, we showed that induced expression of mfpA increases the ciprofloxacin Minimal Inhibitory Concentration. These results confirm that increased expression of the mfpA gene, which is part of the mfpEA operon, increases ciprofloxacin resistance in M. smegmatis.

Antibiotic resistance is one of the main challenges worldwide due to the high morbidity and mortality caused by infections produced by resistant bacteria. In Colombia, this problem has been studied mainly from the clinical perspective; however, it is scarcely studied in the leachates produced in landfills. The objective of this study was to detect, identify and determine the antibiotic sensitivity profile of Enterobacterales isolated from a leachate treatment plant located in Cali, Colombia. Detection was performed using selective culture media, bacterial identification using Matrix-Assisted Laser Desorption/Ionization-Time-Of-Flight (MALDI-TOF, bioMérieux) and by sequencing the gene coding for the 16S ribosomal RNA subunit when discrepancies were observed between phenotypic characteristics and MALDI-TOF. Antibiotic sensitivity profiling was determined using the automated VITEK^®2 system (bioMérieux). Twenty-one isolates were obtained, of which Klebsiella pneumoniae was the most frequent (23.8%), and 34% of the isolates showed decreased sensitivity to beta-lactam antibiotics such as cefoxitin, ampicillin/sulbactam and piperacillin/tazobactam. These findings suggest that leachates from landfills could be a reservoir of pathogenic bacteria carrying antibiotic resistance determinants, so periodic microbiological characterization of these effluents should be performed, promoting the One Health approach.

This study aimed to evaluate the antibiotic resistance of 22 environmental Vibrio metschnikovii isolates and 1 Vibrio injensis isolate from landfill leachates in southwestern Colombia. Isolates were identified by Matrix-Assisted Laser Desorption/Ionization–Time-Of-Flight (MALDI-TOF), and 16S ribosomal RNA gene sequencing. Analysis of the susceptibility to six antibacterial agents by the Kirby–Bauer method showed susceptibility of all the isolates to ciprofloxacin and imipenem. We recorded resistance to beta-lactams and aminoglycosides, but no multidrug resistance was observed. The genome of one of the isolates was sequenced to determine the pathogenic potential of V. injensis. Genes associated with virulence were identified, including for flagellar synthesis, biofilm formation, and hemolysins, among others. These results demonstrate that landfill leachates are potential reservoirs of antibiotic-resistant and pathogenic bacteria and highlight the importance of monitoring Vibrio species in different aquatic environments.