Successful Treatment of Postneurosurgical Ventriculitis Caused by Extensively Drug-resistant Acinetobacter baumannii in a Child: Case Report

Introduction: The incidence of postneurosurgical Acinetobacter baumannii ventriculitis/meningitis, primarily due to drug-resistant strains, has increased considerably in recent years. However, limited therapeutic options are available because most antibiotics poorly penetrate the blood-brain barrier, especially in pediatric patients. Case Presentation: A five-year-old boy developed ventriculitis due to extensively drug-resistant A. baumannii (XDRAB) after bilateral frontal external ventricular drainage for spontaneous intraventricular hemorrhage. The boy was safely and successfully treated with intraventricular (IVT)/intrathecal (ITH) polymyxin B together with intravenous tigecycline plus cefoperazone/sulbactam. Conclusions: In the present case, postneurosurgical XDRAB ventriculitis was closely associated with intraventricular hemorrhage and the placement of external ventricular drainage. IVT/ITH polymyxin B combined with intravenous tigecycline and cefoperazone sulbactam could be a therapeutic option against XDRAB ventriculitis in children.

From Acid Activation Mechanisms of Proton Conduction to Design of Inhibitors of the M2 Proton Channel of Influenza A Virus

With an estimated 1 billion people affected across the globe, influenza is one of the most serious health concerns worldwide. Therapeutic treatments have encompassed a number of key functional viral proteins, mainly focused on the M2 proton channel and neuraminidase. This review highlights the efforts spent in targeting the M2 proton channel, which mediates the proton transport toward the interior of the viral particle as a preliminary step leading to the release of the fusion peptide in hemagglutinin and the fusion of the viral and endosomal membranes. Besides the structural and mechanistic aspects of the M2 proton channel, attention is paid to the challenges posed by the development of efficient small molecule inhibitors and the evolution toward novel ligands and scaffolds motivated by the emergence of resistant strains.

The Central Role of Multiple P450 Genes and Their Co-factor CPR in the Development of Permethrin Resistance in the Mosquito Culex quinquefasciatus

Mosquitoes’ increasing resistance to insecticides is becoming a major threat for control efforts worldwide. Multiple P450 genes that are up-regulated in permethrin resistant strains of Culex quinquefasciatus have been linked to the development of resistance. In the current study, we characterized the function of six P450 genes, CYP6P14, CYP6BZ2, CYP9J33, CYP9J34, CYP9J40, and CYP9J45, that are overexpressed in the permethrin resistant Culex mosquitoes and showed their capability in metabolism of permethrin. These six P450 genes can convert 3-phenoxybenzoic alcohol (PBCHO) to a less toxic product, 3-phenoxybenzoic acid (PBCOOH), indicating that these P450s play an important role in permethrin degradation pathways. Although we know multiple P450 genes are over-expressed in permethrin resistant Culex mosquitoes, it remains to be seen whether cytochrome P450-reductase (CPR) gene that are co-overexpressed with P450 genes in permethrin resistant mosquitoes do indeed serve as a resistance mechanism. An in-depth investigation of the expression of CPR gene in resistant mosquitoes was conducted in permethrin resistant mosquitoes. The finding of CPR gene overexpression in permethrin resistant mosquitoes suggested the importance of co-overexpression of multiple P450 genes with their obligatory electron donor CPR in the complex detoxification system, boosting the metabolism of permethrin and hence the development of permethrin resistance in Cx. quinquefasciatus.

The Effect of Antibiotics on Planktonic Cells and Biofilm Formation Ability of Collected Arcobacter-like Strains and Strains Isolated within the Czech Republic

The purpose of this study was to test the in vitro effects of ampicillin, ciprofloxacin, clindamycin, erythromycin, gentamicin, and tetracycline on planktonic cells of Arcobacter-like microorganisms and on their biofilm formation ability. The minimum inhibitory concentrations (MICs) were determined by the microdilution method. Further, biofilm formation ability in the presence of various concentrations of antibiotics was evaluated by a modified Christensen method. Most of the 60 strains exhibited high susceptibility to gentamicin (98.3%), ciprofloxacin (95.0%), and erythromycin (100.0%). High level of resistance was observed to clindamycin and tetracycline with MIC50 and MIC90 in range of 4–32 mg/L and 32–128 mg/L, respectively. Combined resistance to both clindamycin and tetracycline was found in 38.3% of tested strains. In general, higher biofilm formation was observed especially at lower concentrations of antibiotics (0.13–2 mg/L). However, a significant decrease in biofilm formation ability of Pseudarcobacter defluvii LMG 25694 was exhibited with ampicillin and clindamycin at concentrations above 32 or 8 mg/L, respectively. Biofilm formation represents a potential danger of infection and also a risk to human health, in particular due to antimicrobial-resistant strains and the ability to form a biofilm structure at a concentration that is approximately the MIC determined for planktonic cells.

Hydrophilic nanoparticles that kill bacteria while sparing mammalian cells reveal the antibiotic role of nanostructures

To dissect the antibiotic role of nanostructures from chemical moieties belligerent to both bacterial and mammalian cells, here we show the antimicrobial activity and cytotoxicity of nanoparticle-pinched polymer brushes (NPPBs) consisting of chemically inert silica nanospheres of systematically varied diameters covalently grafted with hydrophilic polymer brushes that are non-toxic and non-bactericidal. Assembly of the hydrophilic polymers into nanostructured NPPBs doesn’t alter their amicability with mammalian cells, but it incurs a transformation of their antimicrobial potential against bacteria, including clinical multidrug-resistant strains, that depends critically on the nanoparticle sizes. The acquired antimicrobial potency intensifies with small nanoparticles but subsides quickly with large ones. We identify a threshold size (dsilica ~ 50 nm) only beneath which NPPBs remodel bacteria-mimicking membrane into 2D columnar phase, the epitome of membrane pore formation. This study illuminates nanoengineering as a viable approach to develop nanoantibiotics that kill bacteria upon contact yet remain nontoxic when engulfed by mammalian cells.

A multiplex molecular assay for detection of six penA codons to predict decreased susceptibility to cephalosporins in Neisseria gonorrhoeae

The emerging cephalosporin-resistant Neisseria gonorrhoeae poses an urgent threat to the continued efficacy of the last-line monotherapy for gonorrhea. Consequently, high-throughput, accurate, and reasonable molecular assays are urgently needed for strengthening antimicrobial-resistance surveillance in N. gonorrhoeae . In this study, we designed a high-throughput multiplex method that incorporates high-resolution melting technology and is based on a 6-codon assay (among the most parsimonious assays) developed following comprehensive and systematic reviews. The results showed that our method can precisely distinguish specific single-nucleotide polymorphisms in resistance-associated genes with a specificity and sensitivity of 100% and a detection limit as low as 10 copies per reaction. This method can be directly applied to clinical samples without cumbersome culture and successfully predicted all cephalosporin-resistant isolates (sensitivity: 100%). The method presented here represents a technique for rapid testing of antimicrobial resistance and will serve as a valuable tool for tailor-made antimicrobial therapy and for monitoring the transmission of cephalosporin-resistant strains.

Comparative analysis of resistance of main etiological agents of chronic osteomyelitis isolated from association and in monoculture

Introduction. To date, a significant number of works have been published devoted to the analysis of the sensitivity of the leading causative agents of osteomyelitis to modern drugs, however, in the available literature there are no data on a comparative analysis of the antibiotic resistance of bacteria isolated from the osteomyelitis focus from the association and in monoculture. Purpose of the work: to compare the resistance profiles of the leading causative agents of osteomyelitis, depending on the bacterial composition of the focus of infection.Materials and methods. The study included 216 clinical isolates, of which 114 were isolated as part of two-component associations, 102 – in a monoculture from pathological material in patients with chronic osteomyelitis who were treated in the purulent department of National Medical Scientific Centre of Traumatology and Orthopedics n.a. academician G.E. Ilizarov (Kurgan, Russia) from 2018 to 2020. To analyze the resistance profiles, depending on the type of microorganism, modern drugs used in the clinic for the treatment of osteomyelitis were taken into account.Results and its discussion. Effective drugs against P. aeruginosa strains isolated from the association were polymyxin and meropenem, and in monoculture–polymyxin, piperacillin/tazobactam, tobramycin; in relation to strains of K. pneumoniae isolated from the association, it was imipenem, in monoculture – amikacin. S. aureus strains isolated both from the association and in monoculture were highly susceptible to antibacterial drugs.Conclusion. The analysis of the sensitivity of the leading causative agents of osteomyelitis, isolated in monoculture and from the association, to the antibacterial drugs used in the clinic, showed significant differences in the resistance profiles between the groups: for S. aureus strains, 4 antibiotics tested out of 13, for P. aeruginosa strains – 7 out of 13, for K. pneumoniae strains – 12 out of 16. The tested antibacterial drugs were less active against P. aeruginosa and S. aureus strains isolated from associations. In contrast, the percentage of resistant strains of K. pneumoniae was higher among monocultures.

Antibacterial Efficacy of Liposomal Formulations Containing Tobramycin and N-Acetylcysteine against Tobramycin-Resistant Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii

The antibacterial activity and biofilm reduction capability of liposome formulations encapsulating tobramycin (TL), and Tobramycin-N-acetylcysteine (TNL) were tested against tobramycin-resistant strains of E. coli, K. pneumoniae and A. baumannii in the presence of several resistant genes. All antibacterial activity were assessed against tobramycin-resistant bacterial clinical isolate strains, which were fully characterized by whole-genome sequencing (WGS). All isolates acquired one or more of AMEs genes, efflux pump genes, OMP genes, and biofilm formation genes. TL formulation inhibited the growth of EC_089 and KP_002 isolates from 64 mg/L and 1024 mg/L to 8 mg/L. TNL formulation reduced the MIC of the same isolates to 16 mg/L. TNL formulation was the only effective formulation against all A. baumannii strains compared with TL and conventional tobramycin (in the plektonic environment). Biofilm reduction was significantly observed when TL and TNL formulations were used against E. coli and K. pneumoniae strains. TNL formulation reduced biofilm formation at a low concentration of 16 mg/L compared with TL and conventional tobramycin. In conclusion, TL and TNL formulations particularly need to be tested on animal models, where they may pave the way to considering drug delivery for the treatment of serious infectious diseases.

Antibacterial Activity of Pharmaceutical-Grade Rose Bengal: An Application of a Synthetic Dye in Antibacterial Therapies

Rose bengal has been used in the diagnosis of ophthalmic disorders and liver function, and has been studied for the treatment of solid tumor cancers. To date, the antibacterial activity of rose bengal has been sporadically reported; however, these data have been generated with a commercial grade of rose bengal, which contains major uncontrolled impurities generated by the manufacturing process (80–95% dye content). A high-purity form of rose bengal formulation (HP-RBf, >99.5% dye content) kills a battery of Gram-positive bacteria, including drug-resistant strains at low concentrations (0.01–3.13 μg/mL) under fluorescent, LED, and natural light in a few minutes. Significantly, HP-RBf effectively eradicates Gram-positive bacterial biofilms. The frequency that Gram-positive bacteria spontaneously developed resistance to HP-RB is extremely low (less than 1 × 10−13). Toxicity data obtained through our research programs indicate that HP-RB is feasible as an anti-infective drug for the treatment of skin and soft tissue infections (SSTIs) involving multidrug-resistant (MDR) microbial invasion of the skin, and for eradicating biofilms. This article summarizes the antibacterial activity of pharmaceutical-grade rose bengal, HP-RB, against Gram-positive bacteria, its cytotoxicity against skin cells under illumination conditions, and mechanistic insights into rose bengal’s bactericidal activity under dark conditions.