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Given the recognized major problem of microbial drug resistance for human health, new metal-based drugs have been currently explored for their antimicrobial properties, including gallium-based compounds as potential metallophores that could perturb Fe's interactions with proteins. Herein we have designed and synthesized two bis-kojate ligands (named L4 and L6) and studied their Ga(III) complexes for their physico-chemical and biological properties. In particular a detailed study of their complexation properties in aqueous solution, showed equilibrium models with formation of quite stable dinuclear 2:3 metal:ligand complexes, though with different stability. Solid state complexes were also prepared and characterized and complementary DFT studies indicated that [Ga 2 (L4) 3 ] complex, with higher stability, seems to adopt a three-ligand bridging conformation, while that for L6 adopt a one ligand bridging conformation. Preliminary investigation of the antibacterial activity of these gallium complexes showed antipseudomonal activity, which appeared higher for the complex with L4, a feature of potential interest for the scientific community., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nucleotides are important to cell growth and division and are crucial to the rapid proliferation of such cells as the intestinal mucosa and immune cells. Accordingly, the nucleotide requirements of animals are high during periods of rapid growth and periods of stress like post-weaning period. Thus, nucleotide supplementation may be a possible alternative to in-feed antibiotics as growth promoter in this phase. The study aimed to evaluate dietary nucleotide supplementation as an alternative to in-feed antibiotics on performance and gut health of weaned piglets. Ninety-six 21-day-old piglets, weighing 7.44 ± 0.65 kg, were allocated into 1 of 3 treatments (8 pens per treatment; 4 pigs per pen) in a 14-day trial. Dietary treatments consisted of control: corn-soybean meal-based diet; nucleotides: control +2 g/kg of a nutritional additive with purified nucleotides; and antibiotic: control +0.8 g/kg of antibiotic growth promoter based on colistin and tylosin. Performance variables and fecal score were not affected (P > 0.05) by supplementing nucleotide or antibiotic. Nucleotides treatment had similar effect to antibiotic and superior to control (P < 0.05) on enhancing duodenum villus height, jejunum crypt depth, and reduction of Paneth cellular area. Duodenum and ileum of animals supplemented with nucleotides or antibiotics had higher (P < 0.05) number of proliferating cells than did those of control animals, whereas the jejunum of animals that received antibiotic diets presented more (P < 0.05) proliferating cells than either the nucleotides or control animals. Jejunum of nucleotide-treated piglets showed a greater number of apoptotic cells than those fed antibiotic or control diets (P < 0.05). Nucleotides and antibiotic treatments decreased the B lymphocyte counts in duodenum and ileum (P < 0.05) but increased in the jejunum (P < 0.05), when compared to the control treatment. Relative abundance of mitogen-activated protein kinases-6, haptoglobin, and tumor necrosis factor-α mRNA was not influenced (P > 0.05) by treatments. In the ileal, antibiotic supplementation reduced total bacteria quantification compared to nucleotide supplementation or the control (P < 0.05), whereas nucleotides supplementation increased enterobacteria proliferation compared to the antibiotic or control diets (P < 0.05). However, nucleotides and antibiotic reduced (P < 0.05) colon total bacteria quantification when compared to control. These results suggest that the nucleotides source used to weaned piglets improved gut health by modulating the local immune response and modulating intestinal mucosa development, and, therefore, nucleotides may be an alternative to antibiotics as growth promoters., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Peritonitis remains a common complication of peritoneal dialysis (PD). The aim of this study was to analyze, in a PD center, long-term temporal trends in peritonitis rates, microbiology and outcomes. We treated 588 cases of peritonitis that occurred during 11,833.6 months at risk. Y-set and twin-bag disconnecting systems were introduced in 1990, mupirocin at the exit site in 2000 and fluconazole prophylaxis in 2005. Vancomycin and ceftazidime were the empiric protocol. Global and 5-year cohort rates were expressed as episodes/patient-year (ep/p-y). A global peritonitis rate reduction was found from 1.02 to 0.47 ep/p-y (p = 0.008). Poisson analyses performed in each of the subgroups of Gram-positive and Gram-negative peritonitis revealed no significant changes over time. No case of vancomycin resistance was identified. There was a downward trend in peritonitis-related hospitalization over time to 0.11 ep/p-y (p ≤ 0.001). Trend analysis showed a favorable, but changing evolution, highlighting the importance of accurate longitudinal PD center registry data and quality control., (Copyright © 2012 S. Karger AG, Basel.)

The use of pathogenic-specific antimicrobials, as proposed by bacteriophage therapy, is expected to reduce the incidence of resistance development. Eighty Escherichia coli isolated from uteri of Holstein dairy cows were phenotypically characterized for antimicrobial resistance to ampicillin, ceftiofur, chloramphenicol, florfenicol, spectinomycin, streptomycin, and tetracycline by broth microdilution method. The lytic activity of a bacteriophage cocktail against all isolates was performed by a similar method. Additionally, the effect of different concentrations of antimicrobials and multiplicities of infections (MOI) of the bacteriophage cocktail on E. coli growth curve was measured. Isolates exhibited resistance to ampicillin (33.7%), ceftiofur (1.2%), chloramphenicol (100%), and florfenicol (100%). All strains were resistant to at least 2 of the antimicrobial agents tested; multidrug resistance (>or=3 of 7 antimicrobials tested) was observed in 35% of E. coli isolates. The major multidrug resistance profile was found for ampicillin-chloramphenicol-florfenicol, which was observed in more than 96.4% of the multidrug-resistant isolates. The bacteriophage cocktail preparation showed strong antimicrobial activity against multidrug-resistant E. coli. Multiplicity of infection as low as 10(-4) affected the growth of the E. coli isolates. The ratio of 10 bacteriophage particles per bacterial cell (MOI=10(1)) was efficient in inhibiting at least 50% of all isolates. Higher MOI should be tested in future in vitro studies to establish ratios that completely inhibit bacterial growth during longer periods. All isolates resistant to florfenicol were resistant to chloramphenicol and, because florfenicol was recently introduced into veterinary clinics, this finding suggests that the selection pressure of chloramphenicol, as well as other antimicrobials, may still play a relevant role in the emergence and dissemination of florfenicol resistance in E. coli. The bacteriophage cocktail had a notable capacity to inhibit the in vitro growth of E. coli isolates, and it may be an attractive alternative to conventional treatment of metritis by reducing E. coli in uteri of postpartum dairy cows., (Copyright 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

An active chloramphenicol efflux system was demonstrated in a multiresistant E. coli isolated from poultry carcass. The effect of different concentrations of chloramphenicol on the original strain and on the plasmid-cured strain was determined in the presence and in the absence of CCCP, an uncoupler of the proton-motive force. Minimal inhibitory concentration (MIC) was lower in the presence of CCCP in the original strain. The plasmid-cured strain displayed lower resistance for chloramphenicol than the wild type, but the MIC was not affected by CCCP. The combined results indicate a plasmid encoded energy dependent resistance mechanism. 3H-chloramphenicol accumulation within the cells was measured by scintillation counting. The uptake or the efflux of 3H-chloramphenicol was influenced by CCCP in the original strain, but not in the plasmid-cured strain. More than one chloramphenicol resistance mechanism may exist in this strain. E. coli is an important commensal or pathogen that inhabits the gastrointestinal tracts of humans and animals, so a plasmid encoded active drug resistance mechanism can be a potential source of horizontal transfer of resistance.

A total of 357 clinical Streptococcus pyogenes isolates collected between 1994 and 1999 in Rio de Janeiro city were tested for susceptibility to 10 antimicrobial drugs by agar-diffusion tests. All isolates were susceptible to penicillin, cephems, and vancomycin. High resistance rates were observed for tetracycline (43.1%) and trimethoprim/sulfamethoxazole (77.9%). Three isolates (0.8%) were resistant to erythromycin, and three exhibited intermediate susceptibility. Determination of the erythromycin MICs by the agar dilution method, showed 1.6% of erythromycin resistant isolates (the three erythromycin-resistant and the three erythromycin-intermediate isolates found by agar-diffusion test). Of the erythromycin-resistant isolates subjected to the double-disc diffusion test for erythromycin and clindamycin, three isolates expressed the iMLSB and three the M phenotype. The resistance phenotypes were confirmed by comparing the clindamycin MICs determined under normal testing conditions and those determined after induction by pre-growth in 0.06 microg/ml of erythromycin. Three ermTR and three mefA-containing isolates were detected by PCR. In strains belonging to the iMLSB phenotype, two clones were identified by PFGE following restriction with SmaI. M phenotype isolates could not be restricted with SmaI. Our results indicate a low rate of erythromycin resistance among S. pyogenes isolated in Rio de Janeiro, Brazil, and pointed to the presence of both resistance mechanisms found in streptococci.

Reports of staphylococci with reduced susceptibility to glycopeptides are cause for concern. This study evaluated the susceptibility of 84 staphylococci clinical isolates to glycopeptides by the disk diffusion, agar dilution, E-test, and BHIA screening methods. Vancomycin agar dilution showed all strains presented minimum inhibitory concentration (MIC) ranging from 0.5 to 2 microg/ml, and the E-test showed similar results. Teicoplanin agar dilution test showed MICs ranging from < or = 0.5 to 2 microg/ml for Staphylococcus aureus and MICs ranging from <0.25 to 32 microg/ml for coagulase-negative Staphylococcus (CNS). Ten CNS isolates presented MICs ranging from 8 to 32 microg/ml for agar dilution and/or E-test. All the staphylococci were susceptible to vancomycin by the disk diffusion test (DDT), but two CNS isolates presented intermediate resistance to teicoplanin by the DDT and MICs of susceptibility, with two other CNS strains, teicoplanin-susceptible by the DDT, presented MICs of intermediate resistance. On the vancomycin-containing agar, 20 CNS isolates were able to grow, but no S. aureus strain. All these isolates showed MICs to teicoplanin (4-32 microg/ml) higher than those isolates that did not grow on the agar screen plate. PFGE of chromosomal SmaI digests showed a wide diversity of these CNS strains, without any predominance of a single PFGE pattern.

Helicobacter pylori resistance to metronidazole was detected in 107 (52.97%) of 202 strains. Twenty (9.85%) strains, 18 of them harboring 23S ribosomal DNA mutations, were resistant to clarithromycin. Metronidazole resistance was associated with female gender. Resistance to metronidazole and resistance to clarithromycin were associated. Increasing clarithromycin resistance rates were observed over time.

The in vitro antimicrobial susceptibility of the respiratory pathogens Streptococcus Pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis to commonly tested and prescribed agents was investigated during 1999-2000 and compared with results obtained during a previous 1997-1998 study. Of 448 isolates of S. Pneumoniae collected and tested in 1999-2000, 77.2% were susceptible, 19.9% were intermediate, and 2.9% were resistant to penicillin, demonstrating that there were no major changes in susceptibility to penicillin from 1997-1998 (77.1% susceptible, 18.7% intermediate, 4.2% resistant). All S. Pneumoniae isolates from 1999-2000 were susceptible to levofloxacin and vancomycin and >90% were susceptible to the B-lactams (amoxicillin-clavulanate, ceftriaxone, and cefuroxime) and macrolides (axithyromycin and clarithromycin), showing that susceptibility to these agents also remained unchanged since 1997-1998. The most notable increase in resistance between the two studies was demonstrated by trimethoprim-sulfamethoxazole, which increased from 23.4% to 38.6%. Penicillin resistance correlated with resistance to B-lactams, macrolides, and trimethoprim-sulfamethoxazole in both studies. In H. influenzae, the prevalence of B-lactamase-producing isolates remained unchanged (10.6% in 1999-2000; 11.0% in 1997-1998). All H. influenzae isolates were susceptible to levofloxacine, ceftriaxone, cefuroxime, and azithromycin, and showed no change between the two studies. Trimethoprim-sulfamethoxazole resistance was present in 40.1% of isolates in 1999-2000, and in 45.2% in 1997-1998. In M. catarrhalis, the prevalence of B-lactamase-producing isolates was unchanged (97.9% in 1999-2000;98.0% in 1997-1998). The most active agents against M. catarrhalis were azithromycin (MIC(90),< or = 0.03 microg/ml) and levofloxacin (MIC(90),< or = 0.03 microg/ml). Overall, these results suggest that, in Brazil, between 1999-2000 and 1997-1998, there have been no significant changes in the susceptibility of respiratory pathogens to any of the commonly tested and prescribed agents with the exception of trimethoprim-sulfamethoxazole for S. Pneumoniae.

Objective: To determine the degree to which bioactive penicillin, metronidazole, ceftriaxone, clindamycin, vancomycin, and gentamicin penetrate into empyemic pleural fluid using our new rabbit model of empyema., Methods: An empyema was created via the intrapleural injection of 10(8)()Pasteurella multocida bacteria into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, penicillin, 24,000 U/kg; metronidazole, 37 mg/kg; ceftriaxone, 30 mg/kg; clindamycin, 9 mg/kg; vancomycin, 15 mg/kg; or gentamicin, 1 mg/kg, were administered IV. Antibiotic levels in samples of pleural fluid and serum, collected serially for up to 480 min, were then determined using a bioassay., Results: The degree to which the different antibiotics penetrated into the infected pleural space was highly variable. Penicillin penetrated most easily, followed by metronidazole, ceftriaxone, clindamycin, vancomycin, and gentamicin. Of the antibiotics tested, penicillin and metronidazole equilibrated the most rapidly with the infected pleural fluid. Penicillin levels remained elevated in pleural fluid even after serum levels had decreased., Conclusions: Using this rabbit model of empyema, there was marked variation in the penetration of antibiotics into the empyemic fluid. Although there are species differences between rabbit and human pleura, the variance in degree of penetration of antibiotics into the pleural space should be considered when antibiotics are selected for the treatment of patients with empyema.

Objective: To assess the susceptibility of the key respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis to antimicrobial agents used to treat respiratory tract infections., Methods: Isolates were collected from five centers in Brazil during 1997-98, and susceptibility testing was conducted at a central laboratory according to National Committee for Clinical Laboratory Standards criteria., Results: Of the 359Streptococcus pneumoniae isolates tested, 77% were susceptible, 19% were intermediate and 4% were resistant to penicillin. The susceptibility of S. pneumoniae to other beta-lactams and macrolides was greater than 90%, but cotrimoxazole was active against only 48% of the isolates. The prevalence of susceptible isolates was 100.0% for vancomycin and 99.7% for levofloxacin. beta-Lactam, macrolide, and cotrimoxazole activities were negatively associated with penicillin resistance. Of the 219 isolates of Haemophilus influenzae tested, 11% produced beta-lactamase and 11% were not susceptible to ampicillin. Nearly all H. influenzae isolates were susceptible to all other drugs, except cotrimoxazole (47% susceptibility). Of the 52 Moraxella catarrhalis isolates, 98% produced beta-lactamase, and the MIC of all drugs was 8 mg/L., Conclusions: When these data are compared with previous reports, our findings suggest that the prevalence of pneumococci that are resistant to agents such as penicillin and cotrimoxazole may be increasing in Brazil, which highlights the need to continue surveillance programs.

Mupirocin is a topical antimicrobial agent that has been successfully used to eradicate methicillin-resistant Staphylococcus aureus from the anterior nares and other sites of patients and health care personnel. This report describes the acquisition of a novel mupirocin resistance gene (ileS) by an epidemic MRSA clone that is geographically widespread in Brazil.

The VanC phenotype, as found in Enterococcus gallinarum, E. casseliflavus, and E. flavescens, is characterized by intrinsic low-level resistance to vancomycin. The nucleotide sequences of the vanC-1 gene in E. gallinarum, the vanC-2 gene in E. casseliflavus, and the vanC-3 gene in E. flavescens have been reported, although there is some disagreement as to whether E. flavescens is a legitimate enterococcal species. Previous attempts to differentiate the vanC-2 and vanC-3 genes by PCR analysis have been unsuccessful. The purpose of the present study was to detect and differentiate the three vanC determinants and examine the distribution of these genes in a collection of both typical and atypical enterococci. The 796-bp vanC-1 PCR product was amplified only from E. gallinarum isolates. As expected, due to the extensive homology in the vanC-2 and vanC-3 gene sequences, all of the E. casseliflavus and E. casseliflavus/flavescens isolates produced the 484-bp vanC-2 PCR product, although the E. gallinarum isolates were negative. Only the E. casseliflavus/flavescens isolates produced the 224-bp vanC-3 product. Using the three sets of primers, we were able to detect and distinguish the vanC-1, vanC-2, and vanC-3 genes from both typical and atypical enterococci strains. Antimicrobial susceptibility tests and analysis of genomic DNA by pulsed-field gel electrophoresis were also performed, but the results indicated that they were not able to distinguish among strains possessing the three vanC genotypes.

We have reported previously that there is a high incidence of hemothorax and substantial mortality in rabbits that are given tetracycline derivatives intrapleurally. However, such complications have not been reported in humans when pleurodesis is attempted with tetracycline derivatives. One primary difference in the two situations is that a chest tube is placed only in humans. The objective of this study was to evaluate the hypothesis that chest tube placement would prevent the development of hemothoraces and lead to better pleurodesis in rabbits given doxycycline intrapleurally. Eighty New Zealand White male rabbits received doxycycline, 20 mg/kg, in a total volume of 2 mL. One half of the rabbits were randomized to receive a chest tube at the time of the injection and were subjected to pleural fluid aspiration twice daily. The remaining rabbits (control group) received no chest tube and no aspiration. Ten rabbits from each group were killed on days 4, 7, 14, and 28. The intrapleural injection of doxycycline induced the production of large exudative effusions. The insertion of chest tubes prevented the development of hemothorax (0/20 in chest tube group, 15/20 in control group, p<0.001). The insertion of chest tubes was also associated with a significant reduction in mortality and a significant improvement in pleurodesis. When pleurodesis is attempted in rabbits with intrapleural doxycycline, the insertion of a chest tube will prevent hemothorax and lead to a better pleurodesis.

Despite all medical advances of this century, pneumonia is still a common condition and the sixth leading cause of mortality in the United States. A pleural effusion develops in up to 40% of cases of pneumonia and empyema in 5% to 10% of those patients. The morbidity and mortality rates in patients with pleural effusions as a consequence of pneumonia are higher than in patients with pneumonia alone. In this review we discuss the classification, bacteriology, and the appropriate antibiotic treatment of patients with parapneumonic pleural effusions.

A total of 107 Enterococcus strains, 10 Vagococcus fluvialis strains, and 8 Lactococcus garvieae strains were tested for acidification of methyl-alpha-D-glucopyranoside (MGP) and susceptibility to 100-microg efrotomycin (EFRO) disks. All 26 strains of Enterococcus casseliflavus, including 3 nonmotile and 2 nonpigmented strains, acidified MGP and were resistant to EFRO. All 22 strains of Enterococcus gallinarum, including 5 nonmotile strains, also acidified MGP and were resistant to EFRO. None of the 26 strains of Enterococcus faecium acidified MGP, and all were susceptible to EFRO. Although all 12 Enterococcus faecalis strains were also negative in the MGP test, they were resistant to EFRO. Other enterococcal strains gave variable results. All 10 strains of V. fluvialis and all 8 strains of L. garvieae gave positive and negative results, respectively, in the MGP test and were, respectively, resistant and susceptible to EFRO. These results indicate that tests of the production of acid from MGP and susceptibility to EFRO can be used as adjunct tests in the identification of typical and atypical strains of enterococci in the clinical microbiology laboratory.