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1.
Biomater Adv ; 137: 212846, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35929275

RESUMO

Despite recent advances in medical technology, treatment of chronic osteomyelitis in the small joint of the hand remains challenging. Here, we exploited hybrid biodegradable hydrogel/microparticle/polycaprolactone (PCL) sacs for finger joint interpositional arthroplasty via electrospraying and rotational molding techniques. Degradable Pluronic F127, poly(lactic-co-glycolic acid) (PLGA), and PCL were starting materials for the hydrogels, microparticles, and sac, respectively. Vancomycin, ceftazidime, and lidocaine were the embedded pharmaceuticals. The in vitro and in vivo drug release behaviors of hybrid drug-eluting sacs were assessed. The empirical outcomes show that the size distribution of the electrosprayed vancomycin/ceftazidime/lidocaine PLGA microparticles was 8.25 ± 3.35 µm. Biodegradable PCL sacs offered sustainable and effective release of vancomycin, ceftazidime, and lidocaine, respectively, after 30, 16, and 11 days in vitro. The sacs also discharged high levels of anti-microbial agents for 56 days and analgesics for 14 days in a rabbit knee joint model. The blood urea nitrogen (creatinine) levels remained normal at various time points: 16.5 ± 2.5 mg/dL (0.85 ± 0.24 mg/dL), 20.0 ± 1.4 mg/dL (1.0 ± 0.16 mg/dL), 19.3 ± 2.4 mg/dL (1.13 ± 0.15 mg/dL), and 20.0 ± 2.16 mg/dL (1.0 ± 0.16 mg/dL) at days 7, 14, 21, and 35, respectively. The empirical outcomes of this study suggested that the hybrid biodegradable drug-eluting sacs with extended liberation of pharmaceuticals may find applications in the small joints for post-operative pain relief and infection control.


Assuntos
Hidrogéis , Vancomicina , Animais , Artroplastia , Ceftazidima , Articulações dos Dedos , Lidocaína , Coelhos
2.
Front Cell Infect Microbiol ; 12: 926209, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35811669

RESUMO

Aztreonam/avibactam (AZA), as one of the novel ß-lactamases and ß-lactamase inhibitor combinations, is considered to be a promising option for bloodstream infection (BSI) of carbapenem-resistant Klebsiella pneumoniae (CR-Kp). However, decreased susceptibility of AZA activity in Enterobacterales has been reported. The aim of this study was to identify the mechanisms of BSI CR-Kp with decreased susceptibility of AZA (minimal inhibitory concentration above 16/4 mg/L) (AZAH-Kp). Nine BSI AZAH-Kp isolates were screened from 317 CR-Kp isolates in Blood Bacterial Resistant Investigation Collaborative System (BRICS) program. Whole genome sequencing, bioinformatics analysis, and the relative expression of blaKPC , ompK35, and ompK37 were explored for CR-Kp with decreased susceptibility to AZA. The results revealed that elevated inhibitory concentration of AZA has emerged in CR-Kp before previous clinical exposure. In addition, decreased AZA susceptibility was associated with higher KPC expression and changes in OmpK35-37.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Sepse , Antibacterianos/uso terapêutico , Compostos Azabicíclicos , Aztreonam/metabolismo , Aztreonam/farmacologia , Proteínas de Bactérias/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Carbapenêmicos/farmacologia , Ceftazidima/farmacologia , Combinação de Medicamentos , Genômica , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , beta-Lactamases/genética , beta-Lactamases/metabolismo
3.
Diagn Microbiol Infect Dis ; 104(1): 115745, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35843111

RESUMO

Ceftazidime-avibactam exhibits good in vitro activity against carbapenem resistant Klebsiella carrying OXA-48-like enzymes. We tested two hundred unique carbapenem resistant Klebsiella blood stream isolates (71% with single OXA-48-like carbapenemases, including OXA-48, n = 62; OXA-232, n = 57; OXA-244, n = 17; OXA-181, n = 5) that were collected as part of a multicentre study against ceftazidime-avibactam using Etest (bioMérieux, Marcyl'Étoile, France), 10/4 µg disc (Thermo Fisher) and Sensititre Gram Negative EURGNCOL Plates (Lyophilized panels, Sensititre, Thermo Fisher) with the aim of comparing the performances of the Etest and disc to that of Sensititre. Ceftazidime-avibactam MIC50/90 was 2/>16 mg/L for the entire collection and was 2/4 mg/L for single OXA-48-like producers. Categorical and essential agreements between the Etest and Sensititre were 100% and 97%, respectively. Categorical agreement between the disc and Sensititre was 100%. Etest and 10/4 µg discs are suitable alternatives to Sensititre for ceftazidime-avibactam sensitivity testing for OXA-48-like producers.


Assuntos
Antibacterianos , Klebsiella , Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Carbapenêmicos , Ceftazidima/farmacologia , Combinação de Medicamentos , Humanos , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , beta-Lactamases
4.
Rev Chilena Infectol ; 39(2): 109-116, 2022 04.
Artigo em Espanhol | MEDLINE | ID: mdl-35856982

RESUMO

BACKGROUND: There is an increase of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in the pediatric population and epidemiological data are limited. AIM: To calculate the frequency of CRKP in pediatric patients, to determine the in vitro activity of colistin and to detect the presence of mcr-1 gene in said isolates. METHODS: 220 isolates of K. pneumoniae were studied in a pediatric hospital between January 2018 and December 2019. Antimicrobial susceptibility was determined by microdilution in broth according to guidelines of CLSI and EUCAST. The genes blaKPC, blaNDM, blaIMP, blaVIM, blaOXA-48 and mcr-1 were detected by polymerase chain reaction (PCR). RESULTS: 9.5% (n: 21) of the isolates were characterized as CRKP, where was observed a resistance to colistin of 47.6% (10/21) with values of MIC50 of 2 µg/mL and MIC90 of ≥ 4 µg/mL. In 100% of CRKP strains the blaKPC gene was detected and the mcr-1 gene was not found. The resistance profile to other antimicrobials was as follow: gentamicin 100% (n: 21), trimethoprim/sulfamethoxazole 100% (n: 21), ciprofloxacin 100% (n: 21), amikacin 19% (n: 4). All of the isolates were sensitive to ceftazidime/avibactam and tigecycline. CONCLUSION: This study demonstrates a significant value of resistance to colistin in pediatric patients compared to other last line antimicrobial such as ceftazidime/avibactam and tigecycline.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Argentina , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Ceftazidima , Criança , Colistina/farmacologia , Hospitais Pediátricos , Humanos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Tigeciclina , beta-Lactamases/genética
5.
Sci Rep ; 12(1): 11120, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35778482

RESUMO

The latest coronavirus pandemic (SARS-CoV-2) poses an exceptional threat to human health and society worldwide. The coronavirus (SARS-CoV-2) spike (S) protein, which is required for viral-host cell penetration, might be considered a promising and suitable target for treatment. In this study, we utilized the nonalkaloid fraction of the medicinal plant Rhazya stricta to computationally investigate its antiviral activity against SARS-CoV-2. Molecular docking and molecular dynamics simulations were the main tools used to examine the binding interactions of the compounds isolated by HPLC analysis. Ceftazidime was utilized as a reference control, which showed high potency against the SARS-CoV-2 receptor binding domain (RBD) in an in vitro study. The five compounds (CID:1, CID:2, CID:3, CID:4, and CID:5) exhibited remarkable binding affinities (CID:1, - 8.9; CID:2, - 8.7; and CID:3, 4, and 5, - 8.5 kcal/mol) compared to the control compound (- 6.2 kcal/mol). MD simulations over a period of 200 ns further corroborated that certain interactions occurred with the five compounds and the nonalkaloidal compounds retained their positions within the RBD active site. CID:2, CID:4, and CID:5 demonstrated high stability and less variance, while CID:1 and CID:3 were less stable than ceftazidime. The average number of hydrogen bonds formed per timeframe by CID:1, CID:2, CID:3, and CID:5 (0.914, 0.451, 1.566, and 1.755, respectively) were greater than that formed by ceftazidime (0.317). The total binding free energy calculations revealed that the five compounds interacted more strongly within RBD residues (CID:1 = - 68.8, CID:2 = - 71.6, CID:3 = - 74.9, CID:4 = - 75.4, CID:5 = - 60.9 kJ/mol) than ceftazidime (- 34.5 kJ/mol). The drug-like properties of the selected compounds were relatively similar to those of ceftazidime, and the toxicity predictions categorized these compounds into less toxic classes. Structural similarity and functional group analyses suggested that the presence of more H-acceptor atoms, electronegative atoms, acidic oxygen groups, and nitrogen atoms in amide or aromatic groups were common among the compounds with the lowest binding affinities. In conclusion, this in silico work predicts for the first time the potential of using five R. stricta nonalkaloid compounds as a treatment strategy to control SARS-CoV-2 viral entry.


Assuntos
Apocynaceae , COVID-19 , Plantas Medicinais , COVID-19/tratamento farmacológico , Ceftazidima , Humanos , Simulação de Acoplamento Molecular , SARS-CoV-2
6.
Curr Microbiol ; 79(9): 271, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35881255

RESUMO

Penicillin-binding proteins (PBPs) play an important role in bacterial biofilm formation and are the targets of ß-lactam antibiotics. This study aimed to investigate the effect of the ß-lactam antibiotic ceftazidime (CAZ) at subminimal inhibitory concentration (sub-MIC) on the biofilm formation of Escherichia coli by targeting PBPs. In this study, PBP1a (encoded by mrcA), PBP1b (encoded by mrcB) and PBP3 (encoded by ftsI), which have high affinity for CAZ, were deleted from the E. coli strain. The mrcB mutant showed lower adhesion, biofilm formation and swimming motility, whereas the knockout of mrcA or ftsI had no obvious influence on the biofilm-associated indicators mentioned above. After treatment with sub-MIC of CAZ, the adhesion, biofilm formation and swimming motility of the mrcB-mutant strain were not different or were slightly reduced compared with those of the untreated group. However, sub-MIC of CAZ still significantly inhibited these biofilm-associated indicators in mrcA- and ftsI-mutant strains. In addition, consistent with the bacterial motility results, the deletion of the mrcB gene reduced the flagellar numbers and the expression of flagellar structural genes, but flagellum-related indicators in the mrcB-mutant strain treated with CAZ were similar to those in the untreated group. Bioinformatic analysis showed that CAZ binds to Lys287, Lys274, Glu281, and Arg286 in PBP1b. Taken together, these results suggest that CAZ reduced flagellar synthesis and bacterial motility by binding with PBP1b and thereby inhibited the adhesion and biofilm formation of E. coli.


Assuntos
Infecções por Escherichia coli , Proteínas de Escherichia coli , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biofilmes , Ceftazidima/farmacologia , Escherichia coli , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Proteínas de Ligação às Penicilinas/genética
7.
Sci Rep ; 12(1): 10701, 2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35739211

RESUMO

Burkholderia pseudomallei (B. pseudomallei) is a Gram-negative pathogen that causes melioidosis, a deadly but neglected tropical disease. B. pseudomallei is intrinsically resistant to a growing list of antibiotics, and alternative antimicrobial agents are being sought with urgency. In this study, we synthesize andrographolide-stabilized silver nanoparticles (andro-AgNPs, spherically shaped with 16 nm average diameter) that show excellent antimicrobial activity against B. pseudomallei, including ceftazidime-resistant strains, being 1-3 orders of magnitude more effective than ceftazidime and 1-2 orders of magnitude more effective than other green-synthesized AgNPs. The andro-AgNPs are meanwhile non-toxic to mammalian cell lines. The mode of action of Andro-AgNPs toward B. pseudomallei is unraveled by killing kinetics, membrane neutralization, silver ions (Ag+) release, reactive oxygen species (ROS) induction, membrane integrity, and cell morphology change studies. The antimicrobial activity and mode of action of andro-AgNPs against B. pseudomallei reported here may pave the way to alternative treatments for melioidosis.


Assuntos
Burkholderia pseudomallei , Melioidose , Nanopartículas Metálicas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ceftazidima/farmacologia , Diterpenos , Mamíferos , Melioidose/tratamento farmacológico , Testes de Sensibilidade Microbiana , Prata/farmacologia
8.
Life Sci Alliance ; 5(10)2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35728946

RESUMO

We evaluated the efficacy of ceftazidime or colistin in combination with polyclonal IgM-enriched immunoglobulin (IgM-IG), in an experimental pneumonia model (C57BL/6J male mice) using two multidrug-resistant Pseudomonas aeruginosa strains, both ceftazidime-susceptible and one colistin-resistant. Pharmacodynamically optimised antimicrobials were administered for 72 h, and intravenous IgM-IG was given as a single dose. Bacterial tissues count and the mortality were analysed. Ceftazidime was more effective than colistin for both strains. In mice infected with the colistin-susceptible strain, ceftazidime reduced the bacterial concentration in the lungs and blood (-2.42 and -3.87 log10 CFU/ml) compared with colistin (-0.55 and -1.23 log10 CFU/ml, respectively) and with the controls. Colistin plus IgM-IG reduced the bacterial lung concentrations of both colistin-susceptible and resistant strains (-2.91 and -1.73 log10 CFU/g, respectively) and the bacteraemia rate of the colistin-resistant strain (-44%). These results suggest that IgM-IG might be useful as an adjuvant to colistin in the treatment of pneumonia caused by multidrug-resistant P. aeruginosa.


Assuntos
Pneumonia , Infecções por Pseudomonas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ceftazidima/farmacologia , Ceftazidima/uso terapêutico , Colistina/farmacologia , Colistina/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Imunoglobulina M , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa
9.
BMJ Case Rep ; 15(6)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35732363

RESUMO

We report a patient in his early 70s, with an alleged history of trauma to the right temporal region, following which a swelling developed. A week later, erythematous changes, throbbing pain and occasional fever spikes were noted. A month after the initial trauma, he presented to our institution with necrosed skin over the right temporal region and swelling extending up to the vertex of the skull. The patient was an uncontrolled diabetic and had systemic conditions like chronic obstructive pulmonary disease and chronic kidney disease. A CT scan revealed a collection along the infratemporal space extending into the masticatory space. Routine investigations, blood culture sensitivity, were sent, which revealed the presence of Burkholderia pseudomallei sensitive to ceftazidime and imipenem. Under antibiotic coverage, the treatment was initiated, incision and drainage were done to reduce the bacterial load. However, the patient was lost to underlying systemic conditions and septic shock.


Assuntos
Burkholderia pseudomallei , Melioidose , Antibacterianos/uso terapêutico , Ceftazidima/uso terapêutico , Humanos , Imipenem , Masculino , Melioidose/complicações , Melioidose/diagnóstico , Melioidose/tratamento farmacológico
11.
J Zoo Wildl Med ; 53(2): 424-432, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35758584

RESUMO

Bacterial abscesses are commonly seen in tortoises. The morbidity and the resultant mortality are high. Multifactorial problems, antibiotics misapplication. and antibiotic-resistant bacteria make abscess treatment complicated and ineffective. This study identifies the etiological bacterial species and determines the best antibiotics for abscess treatment in captive tortoises. Sterile swab specimens from 40 tortoises with abscesses were analyzed using the Analytical Profile Index (API) system. Sixty-five bacteria species were identified covering facultative anaerobic gram-negative (n = 30, 46.2%), facultative anaerobic gram-positive (n = 19, 29.2%), and aerobic gram-negative bacteria (n = 16, 24.6%). The antibiotic sensitivity of these bacteria to 30 antibiotics was assessed using the Kirby-Bauer disk-diffusion method. Greater than 80% anaerobic gram-negative bacterial species showed sensitivity to amikacin and ceftazidime. Greater than 80% anaerobic gram-positive bacterial species were sensitive to amoxicillin, ampicillin, carbenicillin, and penicillin. In addition, more than 80% aerobic gram-negative bacterial species were sensitive to ceftazidime, colistin sulphate, amikacin, gentamicin, kanamycin, polymyxin B, and tobramycin. This study provides clinicians significant information for initial antibiotic options, which could elevate the abscess therapy success rate and improve the life quality of tortoises.


Assuntos
Antibacterianos , Tartarugas , Abscesso/veterinária , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Ceftazidima , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana/veterinária
12.
J Antibiot (Tokyo) ; 75(8): 454-462, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35715617

RESUMO

Resistance in Gram-negative organisms has become one of the leading threats in recent years. Of the different mechanisms described in the literature, resistance due to beta-lactamases genes have been overcomed by the use of a beta-lactamase inhibitor in combination with a beta-lactam antibiotic. When this combination is insufficient to counter metallo-beta-lactamases, a third antibiotic, has been added to restore susceptibility. One such recent combination is ceftazidime-avibactam with aztreonam. In this study, 60 isolates of multidrug-resistant organisms producing metallo-beta-lactamases were included to perform in-vitro antibiotic susceptibility testing against ceftazidime-avibactam and aztreonam alone and in combination using three different methods. Individual testing revealed 100% (60/60) resistance to both ceftazidime-avibactam and aztreonam in all the isolates. The disk diffusion method showed an inhibition zone size of 21 mm in all the isolates, with 16 isolates showing an increase in inhibition zone size of >16 mm. In the E-test fixed ratio method, MICs of ceftazidime-avibactam and aztreonam when used alone ranged from 8/4 µg l-1 to ≥256/4 µg l-1 and 16 µg l-1 to 256 µg l-1, respectively, but in combination, these MICs were reduced to 0.016/4 µg l-1 to 2/4 µg l-1 with FIC < 0.5 in all the isolates. Similar results were obtained with the E-test agar dilution method with more than a 16-fold reduction in MIC in all the isolates when avibactam concentration was fixed at 4 µg l-1. All three methods showed a 100% correlation with each other. The current study depicted the usefulness of combining ceftazidime-avibactam with aztreonam against organisms producing metallo-beta-lactamases and that disk diffusion methods can be used as a method for performing in-vitro antibiotic susceptibility testing of this combination.


Assuntos
Aztreonam , Ceftazidima , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Compostos Azabicíclicos/farmacologia , Aztreonam/farmacologia , Ceftazidima/farmacologia , Combinação de Medicamentos , Resistência Microbiana a Medicamentos , Testes de Sensibilidade Microbiana , beta-Lactamases/genética
13.
Pol J Microbiol ; 71(2): 251-256, 2022 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-35716168

RESUMO

Cefoperazone/sulbactam (CSL) and piperacillin/tazobactam (TZP) are commonly used in clinical practice in China because of their excellent antimicrobial activity. CSL and TZP-nonsusceptible Enterobacteriaceae are typically resistant to extended-spectrum cephalosporins such as ceftriaxone (CRO). However, 11 nonrepetitive Enterobacteriaceae strains, which were resistant to CSL and TZP yet susceptible to CRO, were collected from January to December 2020. Antibiotic susceptibility tests and whole-genome sequencing were conducted to elucidate the mechanism for this rare phenotype. Antibiotic susceptibility tests showed that all isolates were amoxicillin/clavulanic-acid resistant and sensitive to ceftazidime, cefepime, cefepime/tazobactam, cefepime/zidebactam, ceftazidime/avibactam, and ceftolozane/tazobactam. Whole-genome sequencing revealed three of seven Klebsiella pneumoniae strains harbored bla SHV-1 only, and four harbored bla SHV-1 and bla TEM-1B. Two Escherichia coli strains carried bla TEM-1B only, while two Klebsiella oxytoca isolates harbored bla OXY-1-3 and bla OXY-1-1, respectively. No mutation in the ß-lactamase gene and promoter sequence was found. Outer membrane protein (Omp) gene detection revealed that numerous missense mutations of OmpK36 and OmpK37 were found in all strains of K. pneumoniae. Numerous missense mutations of OmpK36 and OmpK35 and OmpK37 deficiency were found in one K. oxytoca strain, and no OmpK gene was found in the other. No Omp mutations were found in E. coli isolates. These results indicated that narrow spectrum ß-lactamases, TEM-1, SHV-1, and OXY-1, alone or in combination with Omp mutation, contributed to the resistance to CSL and TZP in CRO-susceptible Enterobacteriaceae. Antibiotic susceptibility tests Antibiotics Breakpoint, (µg/ml) Klebsiella pneumoniae Escherichia cou Klebriehd axyoca E1 E3 E4 E7 E9 E10 E11 E6 E8 E2 E5 CRO ≤1≥4 ≤0.5 ≤0.5 ≤0.5 ≤0.5 1 ≤0.5 1 ≤0.5 ≤0.5 1 1 CAZ 4 ≥16 1 2 1 4 4 4 4 2 4 1 1 FEP ≤2 216 1 1 0.25 1 2 2 2 0.5 2 1 1 AMC ≤8 ≥32 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 CSL ≤16 ≥64 64 64 64 64 ≥128 128 ≥128 64 128 128 ≥128 TZP ≤16 ≥128 ≥256 ≥256 ≥256 ≥256 2256 2256 ≥256 ≥256 ≥256 ≥256 ≥256 FPT ≤2 ≥16 1 0.5 0.06 0.125 2 1 2 0.25 1 0.125 0.25 FPZ ≤2 216 0.25 0.25 0.06 0.125 0.25 0.25 1 0.125 0.25 0.125 0.125 CZA ≤8 216 1 0.5 0.25 0.25 1 0.25 1 0.5 0.5 0.5 0.25 CZT ≤2 28 2 1 0.5 1 2 2 2 1 1 2 2 CROceftriaxone, CAZceftazidime, FEPcefepime, AMC:amoxicillin clavulanic-acid, CSLcefoperazone/sulbactam, TZP:piperadllin/tazobactam, FPT:cefepime tazobactam, FPZ:cefepime/zidebactam, CZA:ceftazidime/avibactam, CZTceftolozane/tazobactam Gene sequencing results Number Strain ST p-Lactamase gene Promoter sequence mutation Omp mutation El Kpn 45 blaSHV-1, blaTEM-lB none OmpK36, OmpK3 7 E3 Kpn 45 blaSHV-1, blaTEM-lB none OmpK36. OmpK3 7 E4 Kpn 2854 blaSHV-1 none OmpK36, OmpK3 7 E7 Kpn 2358 blaSHV-1 - blaTEM-lB none OmpK36, OmpK3 7 E9 Kpn 2358 blaSHV-1. blaTEM-lB none OmpK36. OmpK3 7 E10 Kpn 18 9 blaSHV-1 none OmpK36. OmpK3 7 Ell Kpn 45 blaSHV-1 none OmpK36, OmpK3 7 E6 Eco 88 blaTEM-lB none none ES Eco 409 blaTEM-1B none none E2 Kox 194 blaOXY-1-3 none OmpK36 mutations. OmpK35 and OmpK 37 deficiency E5 Kox 11 blaOXY-1-1 none no OmpK (OmpK3 5, OmpK36 and OmpK37) gene found.


Assuntos
Enterobacteriaceae , beta-Lactamases , Amoxicilina , Antibacterianos/farmacologia , Cefepima , Cefoperazona/farmacologia , Ceftazidima , Enterobacteriaceae/genética , Escherichia coli/metabolismo , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Mutação , Piperacilina/farmacologia , Sulbactam/farmacologia , Tazobactam , beta-Lactamases/genética , beta-Lactamases/metabolismo
14.
Viruses ; 14(6)2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35746731

RESUMO

More than 20% of all Pseudomonas aeruginosa are infected with Pf4-related filamentous phage and although their role in virulence of P. aeruginosa strain PAO1 is well documented, its properties related to therapy are not elucidated in detail. The aim of this study was to determine how phage and antibiotic therapy induce Pf4, whether the released virions can infect other strains and how the phage influences the phenotype of new hosts. The subinhibitory concentrations of ciprofloxacin and mitomycin C increased Pf4 production for more than 50% during the first and sixth hour of exposure, respectively, while mutants appearing after infection with obligatory lytic phage at low MOI produced Pf4 more than four times after 12-24 h of treatment. This indicates that production of Pf4 is enhanced during therapy with these agents. The released virions can infect new P. aeruginosa strains, as confirmed for models UCBPP-PA14 (PA14) and LESB58, existing both episomally and in a form of a prophage, as confirmed by PCR, RFLP, and sequencing. The differences in properties of Pf4-infected, and uninfected PA14 and LESB58 strains were obvious, as infection with Pf4 significantly decreased cell autoaggregation, pyoverdine, and pyocyanin production, while significantly increased swimming motility and biofilm production in both strains. In addition, in strain PA14, Pf4 increased cell surface hydrophobicity and small colony variants' appearance, but also decreased twitching and swarming motility. This indicates that released Pf4 during therapy can infect new strains and cause lysogenic conversion. The infection with Pf4 increased LESB58 sensitivity to ciprofloxacin, gentamicin, ceftazidime, tetracycline, and streptomycin, and PA14 to ciprofloxacin and ceftazidime. Moreover, the Pf4-infected LESB58 was re-sensitized to ceftazidime and tetracycline, with changes from resistant to intermediate resistant and sensitive, respectively. The obtained results open a new field in phage therapy-treatment with selected filamentous phages in order to re-sensitize pathogenic bacteria to certain antibiotics. However, this approach should be considered with precautions, taking into account potential lysogenic conversion.


Assuntos
Inovirus , Fagos de Pseudomonas , Antibacterianos/farmacologia , Biofilmes , Ceftazidima , Ciprofloxacina/farmacologia , Pseudomonas , Fagos de Pseudomonas/genética , Pseudomonas aeruginosa/genética , Tetraciclinas
15.
Medicine (Baltimore) ; 101(24): e29467, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35713457

RESUMO

INTRODUCTION: Thoracic empyema and concomitant bronchopleural fistula are serious complications of pneumonia. The treatment of empyema caused by extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has become increasingly challenging. PATIENTS CONCERNS AND IMPORTANT CLINICAL FINDINGS: A 57-year-old woman with controlled schizophrenia developed hospital-associated bacterial pneumonia secondary to P. aeruginosa on day 13 of hospitalization for brain meningioma surgery. DIAGNOSIS: Chest radiography and computed tomography revealed right-sided necrotizing pneumonia with pneumothorax, a focal soft tissue defect over the right lower chest wall, and a mild right-sided encapsulated pleural effusion with consolidation. XDR-PA was isolated on empyema cultures. INTERVENTIONS: The patient was treated with intrapleural amikacin as a bridge to video-assisted thoracoscopic surgery, followed by novel ceftazidime-avibactam therapy. OUTCOMES: On the 104th day of admission, the patient underwent chest wall debridement and closure. The patient was discharged on day 111. Twenty-eight days after discharge, there were no observable sequelae of empyema. CONCLUSION: Although the minimum inhibitory concentration of ceftazidime-avibactam for XDR-PA is relatively high (8 mg/L), this report emphasizes the efficacy of ceftazidime-avibactam treatment for XDR-PA empyema, as well as the importance of source control.


Assuntos
Empiema Pleural , Infecções por Pseudomonas , Amicacina/uso terapêutico , Antibacterianos , Compostos Azabicíclicos , Ceftazidima , Combinação de Medicamentos , Feminino , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa
16.
J Bacteriol ; 204(7): e0008822, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35758752

RESUMO

This study characterizes a new genetic structure containing a multicopy of a blaVIM-2 variant with an A676C substitution, blaVIM-63. This gene was detected on the chromosome of two carbapenem-resistant clinical strains of Citrobacter freundii ST22 recovered from two patients, separated by a 6-month period, and previously in Pseudomonas aeruginosa ST2242 from the same hospital unit. Short-read sequencing was used to characterize the new variant in both species, and long-read sequencing was used to characterize the genome of C. freundii. On the P. aeruginosa chromosome, the blaVIM-63 gene was inserted between ISPsy 42-type sequences, flanked by an intl1 sequence, nearby aph(3')-VI, and sul1. On the C. freundii chromosome, the blaVIM-63 gene was inserted into a Tn6230-like transposon as a stable five-tandem-repeat multimer, flanked by the same intl1 as in P. aeruginosa. This structure was stable across subcultures and did not change in the presence of carbapenems. The blaVIM-63 gene was cloned into the pCR-Blunt plasmid to study antimicrobial susceptibility patterns and into pET29a for kinetic activity analysis. VIM-63 showed higher Km values than VIM-2 for ceftazidime and cefepime and higher kcat values for cefotaxime, ceftazidime, imipenem, and ertapenem, without differences in MIC values. This is the first study to describe this new variant, VIM-63, in two different species with a chromosomal location integrated into different mobile elements and the first to describe a stable multimer of a metallo-ß-lactamase. Despite the amino acid substitution, the susceptibility pattern of the new variant was similar to that of VIM-2. IMPORTANCE VIM group metallo-ß-lactamases are usually captured by IntI1 integrases. This work describes the detection for the first time of a novel, previously unknown variant of VIM-2, VIM-63. This carbapenemase has been found on the chromosome of two different species, Citrobacter freundii and Pseudomonas aeruginosa, from the same hospital. The adjacent genetic environment of the blaVIM-63 gene would indicate that the capture of this gene by IntI1 has occurred in two different genetic events in each of the species, and in one there has been a stable integration of tandem copies of this gene.


Assuntos
Ceftazidima , Infecções por Pseudomonas , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Cromossomos/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , beta-Lactamases/genética
17.
Microb Drug Resist ; 28(5): 545-550, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35512733

RESUMO

Burkholderia cepacia complex (Bcc) in airways of patients with cystic fibrosis (CF) is associated with an increased morbidity and mortality. A huge range of intrinsic antimicrobial resistances challenges the treatment of Bcc infections. The aim was to assess the susceptibility of Bcc to ceftazidime/avibactam and standard drugs for the treatment for CF patients and to determine the respective genomic determinants of resistance. Bcc isolates (n = 64) from a prospective multicenter study of CF airway pathogens (2004-2020, Germany) were subjected to broth microdilution and minimal inhibitory concentrations were interpreted with European Committee on Antimicrobial Susceptibility Testing and Clinical & Laboratory Standards Institute breakpoints. A synergism between aztreonam and avibactam was tested using ceftazidime/avibactam disks with or without aztreonam. Plasmids and chromosomes of all isolates were screened for antimicrobial resistance genes. The highest susceptibility rate was detected for trimethoprim/sulfamethoxazole (83%), followed by ceftazidime/avibactam (78%), ceftazidime (53%), levofloxacin (39%) and meropenem (27%). The median inhibition zone diameters of ceftazidime-avibactam and ceftazidime/avibactam plus aztreonam were equal. This was in line with the absence of known class B metallo-ß-lactamases in any of the isolates. The majority of isolates carried blapenA (98%) and blaampC (86%). Trimethoprim/sulfamethoxazole and ceftazidime/avibactam showed high susceptibility rates. Aztreonam in combination with ceftazidime/avibactam had no synergistic effect in our Bcc isolates.


Assuntos
Complexo Burkholderia cepacia , Fibrose Cística , Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Compostos Azabicíclicos/uso terapêutico , Aztreonam/farmacologia , Aztreonam/uso terapêutico , Ceftazidima/farmacologia , Ceftazidima/uso terapêutico , Fibrose Cística/tratamento farmacológico , Combinação de Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Estudos Prospectivos , Sulfametoxazol/farmacologia , Trimetoprima/farmacologia
18.
Klin Lab Diagn ; 67(5): 315-320, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35613352

RESUMO

Stenotrophomonas maltophilia is a common opportunistic microorganism and an important respiratory pathogen in cystic fibrosis (CF). The aim of this study was to determine antimicrobial resistance phenotypes, sequence-types (ST) and genetic determinants of antibiotic resistance in S. maltophilia strains recovered from CF patients in Russia. S. maltophilia isolates recovered from 170 CF patients were analyzed. Minimum inhibitory concentrations of antibacterial agents were determined using Sensititre Gram Negative GNX2F plates and the results were interpreted according to Clinical and Laboratory Standards Institute (CLSI) criteria. Whole-genome sequencing (WGS) was performed on MGISEQ-2000 platform. SPAdes software, Galaxy, ResFinder, Integrall and PubMLST were used for analysis of WGS data. S. maltophilia strains were identified from 24/170 (14%) CF patients. In total, 25 isolates were detected, two strains were isolated from the same patient. The isolates belonged to 17 different STs, including 5 new STs; ST4 was the most prevalent ST. Resistance to ceftazidime was observed in 60% of strains, to ticarcillin-clavulanate - in 32%, to levofloxacin - in 24%, to trimethoprim/sulfamethoxazole - in 12% of strains. All isolates were susceptible to minocycline. All ST4 isolates were resistant or intermediate to ceftazidime and ticarcillin-clavulanate. In two isolates, the sul1 gene was detected. In one isolate, sul1 was part of a class 1 integron. The detected integron also contained the blaGES-7 and aac(6')-Ib-cr genes. The ST4 sequence-type was the most prevalent ST among S. maltophilia strains recovered from CF patients in Russia. Antibiotic resistance genes, including sul1, blaGES-7, aac(6')-Ib-cr, were detected in single strains.


Assuntos
Fibrose Cística , Infecções por Bactérias Gram-Negativas , Stenotrophomonas maltophilia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ceftazidima/farmacologia , Ácido Clavulânico , Fibrose Cística/microbiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Stenotrophomonas maltophilia/genética , Ticarcilina
19.
Antimicrob Agents Chemother ; 66(5): e0018922, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35491836

RESUMO

Ceftolozane-tazobactam (C/T), imipenem-relebactam (IMR), and ceftazidime-avibactam (CZA) were tested against 2,531 P. aeruginosa strains isolated from patients in the United States from 2018 to 2020 as part of the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance program. MICs were determined by CLSI broth microdilution and interpreted using CLSI M100 (2021) breakpoints. Imipenem-, IMR-, or C/T-nonsusceptible isolates were screened for ß-lactamase genes: 96.4% of all isolates and ≥70% of multidrug-resistant (MDR), pan-ß-lactam-nonsusceptible, and difficult-to-treat resistance (DTR) isolates were C/T-susceptible; 52.2% of C/T-nonsusceptible isolates remained susceptible to IMR compared to 38.9% for CZA; and 1.7% of isolates tested were nonsusceptible to both C/T and IMR versus 2.2% of isolates with a C/T-nonsusceptible and CZA-resistant phenotype (a difference of 12 isolates). C/T and IMR modal MICs for pan-ß-lactam-nonsusceptible isolates remained at or below their respective susceptible MIC breakpoints from 2018 to 2020, while the modal MIC for CZA increased 2-fold from 2018 to 2019 and exceeded the CZA-susceptible MIC breakpoint in both 2019 and 2020. Only six of 802 molecularly characterized isolates carried a metallo-ß-lactamase, and two isolates carried a GES carbapenemase. Most P. aeruginosa isolates were C/T-susceptible, including many with MDR, pan-ß-lactam-nonsusceptible, DTR, CZA-resistant, and IMR-nonsusceptible phenotypes. While C/T was the most active antipseudomonal agent, IMR demonstrated greater activity than CZA against isolates nonsusceptible to C/T.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Compostos Azabicíclicos/farmacologia , Ceftazidima/farmacologia , Cefalosporinas/farmacologia , Combinação de Medicamentos , Hospitais , Humanos , Imipenem/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/genética , Tazobactam/farmacologia , Estados Unidos , beta-Lactamases/genética
20.
Eur J Clin Microbiol Infect Dis ; 41(6): 989-996, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35596097

RESUMO

Antimicrobial susceptibility of clinical isolates collected from sites in central Europe in 2019 was tested by CLSI broth microdilution method and EUCAST breakpoints. Most active were amikacin, ceftazidime-avibactam and colistin; respectively, susceptibility rates among P. aeruginosa (n = 701) were 89.2%, 92.2% and 99.9%; difficult-to-treat (DTR) isolates, 62.5%, 37.5% and 100%; multidrug-resistant (MDR) isolates, 68.3%, 72.9% and 99.5%; meropenem-resistant (MEM-R), metallo-ß-lactamase-negative (MBL-negative) isolates, 72.8%, 78.6% and 100%. Among Enterobacterales (n = 1639), susceptibility to ceftazidime-avibactam, colistin and tigecycline was ≥ 97.9%; MDR Enterobacterales, 96.8%, 94.4% and 100%, respectively; DTR isolates, ≥ 76.2% to ceftazidime-avibactam and colistin; MEM-R, MBL-negative isolates, ≥ 90.0% to ceftazidime-avibactam and colistin.


Assuntos
Colistina , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Compostos Azabicíclicos , Ceftazidima/farmacologia , Colistina/farmacologia , Croácia , República Tcheca , Combinação de Medicamentos , Enterobacteriaceae , Humanos , Hungria , Letônia , Lituânia , Meropeném , Testes de Sensibilidade Microbiana , Polônia
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