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.

The objectives of this study were to determine the kinetic parameters of purified recombinant Bla _Mab and Bla _Mmas by spectrophotometry, analyze the genetic environment of the bla _Mab and bla _Mmas genes in both species by polymerase chain reaction and sequencing, furthermore, in silico models of both enzymes in complex with imipenem were obtained by modeling tools. Our results showed that Bla _Mab and Bla _Mmas have a similar hydrolysis behavior, displaying high catalytic efficiencies toward penams, cephalothin, and nitrocefin; none of the enzymes are well inhibited by clavulanate. Bla _Mmas hydrolyzes imipenem at higher efficiency than cefotaxime and aztreonam. Bla _Mab and Bla _Mmas showed that their closest structural homologs are KPC-2 and SFC-1, which correlate to the mild carbapenemase activity toward imipenem observed at least for BlaMmas. They also seem to differ from other class A β-lactamases by the presence of a more flexible Ω loop, which could impact in the hydrolysis efficiency against some antibiotics. A −35 consensus sequence (TCGACA) and embedded at the 3′ end of MAB_2874, which may constitute the bla _Mab and bla _Mmas promoter. Our results suggest that the resistance mechanisms in fast-growing mycobacteria could be probably evolving toward the production of β-lactamases that have improved catalytic efficiencies against some of the drugs commonly used for the treatment of mycobacterial infections, endangering the use of important drugs like the carbapenems.

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.

This study presents the synthesis of four series of novel hybrid chalcones (20,21)a–g and (23,24)a–g and six series of 1,3,5-triazine-based pyrimido[4,5-b][1,4]diazepines (28–33)a–g and the evaluation of their anticancer, antibacterial, antifungal, and cytotoxic properties. Chalcones 20b,d, 21a,b,d, 23a,d–g, 24a–g and the pyrimido[4,5-b][1,4]diazepines 29e,g, 30g, 31a,b,e–g, 33a,b,e–g exhibited outstanding anticancer activity against a panel of 60 cancer cell lines with GI₅₀ values between 0.01 and 100 μM and LC₅₀ values in the range of 4.09 μM to >100 μM, several of such derivatives showing higher activity than the standard drug 5-fluorouracil (5-FU). On the other hand, among the synthesized compounds, the best antibacterial properties against N. gonorrhoeae, S. aureus (ATCC 43300), and M. tuberculosis were exhibited by the pyrimido[4,5-b][1,4]diazepines (MICs: 0.25–62.5 µg/mL). The antifungal activity studies showed that triazinylamino-chalcone 29e and triazinyloxy-chalcone 31g were the most active compounds against T. rubrum and T. mentagrophytes and A. fumigatus, respectively (MICs = 62.5 μg/mL). Hemolytic activity studies and in silico toxicity analysis demonstrated that most of the compounds are safe.

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.

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.