Analysis of pathogens and antimicrobial treatment in different groups of patients with chronic otitis media.

OBJECTIVE: Microbial infection plays an important role in exacerbation of chronic otitis media. The aim of this study was to analyse the microbiota in chronic otitis media in the context of local treatment. METHOD: In this prospective study, samples for microbiological examination were taken from 119 patients who underwent operation because of chronic otitis media. RESULTS: The results were compared between groups depending on the type of operation (none, tympanoplasty or radical), the presence of cholesteatoma or granulomatous tissue or discharge from the ear as a symptom of exacerbation. Antibiotic susceptibility of germs was analysed to define the strategy of treatment. A total of 209 samples were collected from 119 patients with chronic otitis media. CONCLUSION: Pseudomonas aeruginosa and Staphylococcus aureus were pathogens most frequently identified from the ear in the course of chronic otitis media. Pseudomonas aeruginosa was concerned with major pathology of the middle ear (radical surgery, cholesteatoma or granulomatous tissue, persisting discharge after treatment), whereas Staphylococcus aureus was obtained in dry perforations without other pathology in the middle-ear cavity. Ciprofloxacin was effective against Staphylococcus aureus, but Pseudomonas aeruginosa strains were ciprofloxacin resistant.

Clinical outcome from hematopoietic cell transplant patients with bloodstream infection caused by carbapenem-resistant P. aeruginosa and the impact of antimicrobial combination in vitro.

Bloodstream infection (BSI) caused by carbapenem-resistant P. aeruginosa (CRPA) has high mortality in hematopoietic stem cell transplant (HSCT) recipients. We performed MIC, checkerboard, time-kill assay, PFGE, PCR, and whole genome sequence and described the clinical outcome through Epi Info comparing the antimicrobial combination in vitro. Mortality was higher in BSI caused by CRPA carrying the lasB virulence gene. The isolates were 97% resistant to meropenem displaying synergistic effect to 57% in combination with colistin. Seventy-three percent of the isolates harbored blaSPM-1 and Tn4371 and belonged to ST277. The synergistic effect in vitro with meropenem with colistin appeared to be a better therapeutic option.

The chemical composition and antibacterial activity of a methanolic extract of Satureja khuzistanica

Abstract In the present study, the metabolite profiling of methanolic extract from aerial parts of Satureja khuzistanica Jamzad, as an endemic medicinal plant from Iran, was evaluated using HPLC-PDA-ESI. Then, the main compound from the extract was isolated and purified by using extensive chromatographic techniques. In addition, the structure of the isolated compounds was elucidated using 1D, 2D NMR, and MS spectrometry, upon which 22 compounds were identified. The antibacterial activity of diosmetin 7-rutinoside (6) and linarin (13) in combination with carvacrol as a major compound of the essential oil was tested against Pseudomonas aeruginosa and Staphylococcus aureus through disc diffusion and minimum inhibitory concentration methods. The results indicated that the linarin, when mixed with carvacrol as the main compounds in the essential oil of the plant, has a satisfactory activity against both Pseudomonas aeruginosa and Staphylococcus aureus with MIC values of 0.16 and 0.18 µg/mL, respectively. Further, the fractional inhibitory concentration (FIC) index indicated that this compound had synergism with carvacrol.

Antimicrobial resistance profiles and associated factors of Acinetobacter and Pseudomonas aeruginosa nosocomial infection among patients admitted at Dessie comprehensive specialized Hospital, North-East Ethiopia. A cross-sectional study.

INTRODUCTION: Hospital admitted patients are at increased risk of nosocomial infections (NIs) with multi-drug resistant (MDR) pathogens which are prevalent in the hospital environment. Pseudomonas aeruginosa (P. aeruginosa) and Acinetobacter baumannii (A. baumannii) are common causes of NIs worldwide. The objective of this study is to determine antimicrobial resistance profiles and associated factors of Acinetobacter spp and P. aeruginosa NIs among hospitalized patients. METHODS: A cross-sectional study was conducted at Dessie comprehensive specialized hospital, North-East Ethiopia, from February 1 to April 30, 2020. A total of 254 patients who were suspected of the bloodstream, urinary tract, or surgical site nosocomial infections were enrolled consecutively. Socio-demographic and other variables of interest were collected using a structured questionnaire. Specimens were collected and processed following standard microbiological procedures. Antimicrobial susceptibility was determined using the Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute guidelines. Data were analyzed with SPSS version 23 and p-value < 0.05 was considered statistically significant. RESULTS: Overall, 13% of patients had nosocomial Acinetobacter spp and/or P. aeruginosa infections. The culture positivity rate was 16(6.3%) for Acinetobacter spp and 18(7.1%) for P. aeruginosa. Patients admitted in the surgical ward (Adjusted odds ratio (AOR):10.66;95% confidence interval (CI):1.22-93.23), pediatric ward (AOR:14.37;95%CI:1.4-148.5), intensive care unit (AOR:41.93;95%CI:4.7-374.7) and orthopedics (AOR:52.21;95%CI:7.5-365) were significantly at risk to develop NIs compared to patients admitted in the medical ward. Patients who took more than two antimicrobial types at admission were 94% (AOR:0.06; 95% CI:0.004-0.84) times more protected from NIs compared to those who did not take any antimicrobial. About 81% of Acinetobacter spp and 83% of P. aeruginosa isolates were MDR. Amikacin and meropenem showed promising activity against Acinetobacter spp and P. aeruginosa isolates. CONCLUSION: The high prevalence of MDR Acinetobacter spp and P. aeruginosa nosocomial isolates enforce treating of patients with NIs based on antimicrobial susceptibility testing results.

Successfully controlling the incidence of multidrug-resistant Pseudomonas aeruginosa through antibiotic stewardship and infection control programmes at a Chinese university hospital.

WHAT IS KNOWN AND OBJECTIVE: The purpose of this study was to investigate the effect of imposing infection control programmes (ICPs) and antimicrobial stewardship (AMS) by monitoring the antimicrobial resistance of Pseudomonas aeruginosa. METHODS: Antimicrobial susceptibility testing was performed in accordance with the Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing guidelines. ICPs and AMS were initiated at the Fourth Hospital from 2013 to 2018. RESULTS AND DISCUSSION: A total of 2,886 P. aeruginosa isolates were assessed. The antimicrobial resistance trends of the P. aeruginosa strains improved after the intervention measures. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) P. aeruginosa contributed to 18.5% and 3.5% of the total P. aeruginosa strains, respectively. Colistin was the most effective antibiotic against 97.6% of XDR-P. aeruginosa and 99.41% of MDR-P. aeruginosa. The consumption of alcohol-based hand gel (ABHG) increased from 0.6 L to 10.8 L per 1,000 patient-days (PD) (p = 0.005). The yearly consumption of antibiotics decreased from 45 to 37.5 defined daily doses (DDD) per 1,000 PD(p = 0.04). After 2013, the incidence rate of MDR-P. aeruginosa showed a significant decrease from 22% to 14.1% (p = 0.04), and XDR-P. aeruginosa decreased from 5.8% to 0.9%. The use of ABHG was negatively related to MDR-P. aeruginosa morbidity (r = -0.86; p = 0.021). The consumption of antibiotics was positively related to MDR-P. aeruginosa morbidity (r = 0.86; p = 0.021). WHAT IS NEW AND CONCLUSION: Successful control of MDR-P. aeruginosa resistance was achieved by imposing comprehensive ICPs and AMS.

Diphenhydramine and levofloxacin combination therapy against antimicrobial resistance in respiratory tract infections.

Background: Antibiotics are in use since decades to treat various infections caused by Gram-positive and Gram-negative bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. Diphenhydramine, an H1 receptor blocker possesses a weak antibiotic action but when combined with other antibiotics may potentiate their antibacterial activity. Materials & methods: This study investigated in vitro antibacterial activity of diphenhydramine when used alone and in combination with levofloxacin against methicillin-resistant S. aureus and P. aeruginosa. Results: The combined antibacterial effect of the drugs against bacteria showed a fractional inhibitory concentration index of ≤0.5, in other words, synergism. No cytotoxicity was observed as percentage cell viability was >50%. Conclusion: The combination of diphenhydramine and levofloxacin exerted antibacterial activity, and was not found to be cytotoxic when given in combination against P. aeruginosa and S. aureus.

Chemotaxis Toward Crude Oil by an Oil-Degrading Pseudomonas aeruginosa 6-1B Strain.

The chemotactic properties of an oil-degrading Pseudomonas aeruginosa strain 6-1B, isolated from Daqing Oilfield, China, have been investigated. The strain 6-1B could grow well in crude oil with a specific rhamnolipid biosurfactant production. Furthermore, it exhibits chemotaxis toward various substrates, including glycine, glycerol, glucose, and sucrose. Compared with another oil-degrading strain, T7-2, the strain 6-1B presented a better chemotactic response towards crude oil and its vital component, n-alkenes. Based on the observed distribution of the strain 6-1B cells around the oil droplet in the chemotactic assays, the potential chemotaxis process of bacteria toward crude oil could be summarized in the following steps: searching, moving and consuming.

Ceftolozane/tazobactam for Pseudomonas aeruginosa pulmonary exacerbations in cystic fibrosis adult patients: a case series.

Management of cystic fibrosis (CF) patients colonized with Pseudomonas aeruginosa is challenging due to its virulence and multi-drug resistance. Ceftolozane/tazobactam (C/T) is a promising new antipseudomonal agent, and clinical data on CF are limited. We describe our experience in the use of C/T for P. aeruginosa-related pulmonary exacerbations (PE) in CF adults admitted within 2016 and 2019 at Careggi Hospital, Florence, Italy. PE was diagnosed as deterioration of respiratory function, worsening cough, and increasing of sputum. C/T was given at the dose of 3 g every 8 h. C/T was used in ten patients. Mean length of C/T treatment was 16.3 days, and tobramycin was the most frequently combined antipseudomonal agent. All patients were successfully treated although susceptibility testing on sputum sample showed C/T resistance in two cases. No adverse effects related to C/T were reported. To our knowledge this is the largest case series on CF patients treated with C/T. Clinical responses were encouraging even where C/T resistant P. aeruginosa was isolated, probably due to multiple phenotypes colonizing CF lungs. C/T could play a promising role in combination therapy against P. aeruginosa as a part of a colistin-sparing regime.

Comparison of Clinical Features and Treatment Outcomes of Pseudomonas aeruginosa Keratitis in Contact Lens and Non-Contact Lens Wearers.

PURPOSE: To compare the outcomes of Pseudomonas aeruginosa keratitis (PAK) in contact lens wearers (CLWs) and non-contact lens wearers (non-CLWs) and identify risk factors for poor visual acuity (VA) outcomes in each group. DESIGN: Retrospective cohort study METHODS: Two hundred fourteen consecutive cases of PAK were included between January 2006 and December 2019. Clinical features, microbiologic results, and treatment course were compared between CLW and non-CLW groups. Analyses of clinical features predicting poor final VA were performed. RESULTS: This study identified 214 infected eyes in 207 patients with PAK, including 163 eyes (76.2%) in CLWs and 51 eyes (23.8%) in non-CLWs. The average age was 39.2 years in CLWs and 71.9 years in non-CLWs (P < .0001). The average logMAR visual acuity (VA) at presentation was 1.39 in CLWs and 2.17 in non-CLWs (P < .0001); average final VA was 0.76 in CLWs and 1.82 in non-CLWs (P < .0001). Stromal necrosis required a procedural or surgical intervention in 13.5% of CLWs and 49.0% of non-CLWs (P < .0001). A machine learning-based analysis yielded a list of clinical features that most strongly predict a poor VA outcome (worse than 20/40), including worse initial VA, older age, larger size of infiltrate or epithelial defect at presentation, and greater maximal depth of stromal necrosis. CONCLUSIONS: Non-CLWs have significantly worse VA outcomes and required a higher rate of surgical intervention, compared with CLWs. Our study elucidates risk factors for poor visual outcomes in non-CLWs with PAK.

Spectrum of Fungal Pathogens in Burn Wound Specimens: Data From a Tertiary Care Hospital Laboratory in Pakistan.

Burn patients are at great risk of developing fungal wound infections. Fungi are frequently cultured from burn tissue specimens alone or in combination with bacteria. However, the spectrum of fungi in burn patients from Pakistan has not been reported previously. A retrospective laboratory-based study was conducted and data on all positive cultures from burn wounds were included. During the study period, specimens were cultured on appropriate media and incubated for anaerobic and aerobic growth. Clinical and demographic information recorded during clinical reporting was also collected. Seventy tissue cultures were positive for microorganisms. Of these, 27 (39%) had growth of either filamentous mold (17 cases) or Candida species (14 cases). Two cases had growth of both mold and yeast. Aspergillus flavus was the most common mold (9) followed by Fusarium species (3). Candida tropicalis was the most common yeast (7) followed by Candida parapsilosis (4). There was concomitant bacterial growth in 19 cases, predominantly of Staphylococcus aureus (13), Pseudomonas aeruginosa (8), and other Gram-negative rods (6). Of the 35 patients in which treatment history was available, 33 were receiving broad-spectrum antibiotics. A high incidence of fungal isolation was seen in this study. Their findings are consistent with the global increase in fungal infections in burn wounds. High index of suspicion by clinicians and revision of culture protocols in burn patients may be warranted for optimal patient management.

Multicenter study of ceftolozane/tazobactam for treatment of Pseudomonas aeruginosa infections in critically ill patients.

BACKGROUND: This study aimed to assess the efficacy of ceftolozane-tazobactam (C/T) for treating infections due to Pseudomonas aeruginosa (P. aeruginosa) in critically ill patients. PATIENTS AND METHODS: A multicenter, retrospective and observational study was conducted in critically ill patients receiving different C/T dosages and antibiotic combinations for P. aeruginosa infections. Demographic data, localisation and severity of infection, clinical and microbiological outcome, and mortality were evaluated. RESULTS: Ninety-five patients received C/T for P. aeruginosa serious infections. The main infections were nosocomial pneumonia (56.2%), intra-abdominal infection (10.5%), tracheobronchitis (8.4%), and urinary tract infection (6.3%). Most infections were complicated with sepsis (49.5%) or septic shock (45.3%), and bacteraemia (10.5%). Forty-six episodes were treated with high-dose C/T (3 g every 8 hours) and 38 episodes were treated with standard dosage (1.5 g every 8 hours). Almost half (44.2%) of the patients were treated with C/T monotherapy, and the remaining group received combination therapy with other antibiotics. Sixty-eight (71.6%) patients presented a favourable clinical response. Microbiological eradication was documented in 42.1% (40/95) of the episodes. The global ICU mortality was 36.5%. Univariate analysis showed that 30-day mortality was significantly associated (P < 0.05) with Charlson Index at ICU admission and the need of life-supporting therapies. CONCLUSIONS: C/T appeared to be an effective therapy for severe infections due to P. aeruginosa in critically ill patients. Mortality was mainly related to the severity of the infection. No benefit was observed with high-dose C/T or combination therapy with other antibiotics.

Actividad antimicrobiana de ceftolozano-tazobactam y ceftazidima-avibactam contra bacilos gramnegativos clínicamente relevantes aislados en México / Ceftolozane/tazobactam and ceftazidime/avibactam antimicrobial activity against clinically relevant gram-negative bacilli isolated in Mexico

Resumen Introducción: Existe poca información acerca de la efectividad de las combinaciones ceftolozano/tazobactam y ceftazidima/avibactam en cepas clínicamente relevantes aisladas en México. Objetivo: Determinar el perfil antimicrobiano de ambos antibióticos en nuestra comunidad. Método: El presente estudio de investigación fue prospectivo, descriptivo y transversal. Se incluyeron cepas clínicamente relevantes aisladas a partir de cultivos de cepa pura durante el periodo de agosto de 2018 a enero de 2019 en Mexicali, Baja California, México. Resultados: Se analizaron 74 cepas de enterobacterias y 19 cepas de Pseudomonas aeruginosa; el porcentaje de sensibilidad de ceftazidima/avibactam fue de 100 % contra enterobacterias y de 72.7 % contra Pseudomonas aeruginosa; el porcentaje de sensibilidad de ceftolozano/tazobactam fue de 90.5 % para enterobacterias y de 72.7 % para Pseudomonas aeruginosa. Conclusiones: Las combinaciones ceftolozano/tazobactam y ceftazidima/avibactam ofrecen buena sensibilidad antimicrobiana in vitro, tanto contra enterobacterias productoras de betalactamasas de espectro extendido como contra Pseudomonas aeruginosa. Se requieren más datos para valorar la respuesta clínica en pacientes que reciben esas combinaciones de antibióticos.

Abstract Introduction: There is limited information on the effectiveness of ceftolozane/tazobactam and ceftazidime/avibactam combinations on clinically relevant strains isolated in Mexico. Objective: To determine the antimicrobial profile of both antibiotic combinations in our community. Method: The present research study was prospective, descriptive and cross-sectional. Clinically relevant strains isolated from pure-strain cultures were included during the period from August 2018 to January 2019 in Mexicali, Baja California, Mexico. Results: 74 enterobacteriaceae and 19 Pseudomonas aeruginosa strains were analyzed; the percentage of sensitivity of ceftazidime/avibactam was 100 % for enterobacteriaceae and 72.7 % for Pseudomonas aeruginosa; the percentage of sensitivity of ceftolozane/tazobactam for enterobacteriaceae was 90.5 % and 72.7 % for Pseudomonas aeruginosa. Conclusions: The ceftolozane/tazobactam and ceftazidime/avibactam combinations offer good antimicrobial sensitivity in vitro, both for ESBL-producing enterobacteriaceae and Pseudomonas aeruginosa. More data are required to assess clinical response in patients receiving these antibiotic combinations.

Major discrepancy between factual antibiotic resistance and consumption in South of France: analysis of 539,037 bacterial strains.

The burden of antibiotic resistance is currently estimated by mathematical modeling, without real count of resistance to key antibiotics. Here we report the real rate of resistance to key antibiotics in bacteria isolated from humans during a 5 years period in a large area in southeast in France. We conducted a retrospective study on antibiotic susceptibility of 539,107 clinical strains isolated from hospital and private laboratories in south of France area from January 2014 to January 2019. The resistance rate to key antibiotics as well as the proportion of bacteria classified as Difficult-to-Treat (DTR) were determined and compared with the Mann-Whitney U test, the χ2 test or the Fisher's exact test. Among 539,037 isolates, we did not observe any significant increase or decrease in resistance to key antibiotics for 5 years, (oxacillin resistance in Staphylococcus aureus, carbapenem resistance in enterobacteria and Pseudomonas aeruginosa and 3rd generation cephalosporin resistance in Escherichia coli and Klebsiella pneumoniae). However, we observed a significant decrease in imipenem resistance for Acinetobacter baumannii from 2014 to 2018 (24.19-12.27%; p = 0.005) and a significant increase of ceftriaxone resistance in Klebsiella pneumoniae (9.9-24.03%; p = 0.001) and Enterobacter cloacae (24.05-42.05%; p = 0.004). Of these 539,037 isolates, 1604 (0.3%) had a DTR phenotype. Over a 5-year period, we did not observe a burden of AR in our region despite a high rate of antibiotic consumption in our country. These results highlight the need for implementation of real-time AR surveillance systems which use factual data.

Fatal respiratory infection due to ST308 VIM-1-producing Pseudomonas aeruginosa in a lung transplant recipient: case report and review of the literature.

BACKGROUND: Data regarding the prevalence of metallo-ß-lactamases (MBLs) among Pseudomonas aeruginosa isolates in cystic fibrosis patients are scarce. Furthermore, there is limited knowledge on the effect of MBL production on patient outcomes. Here we describe a fatal respiratory infection due to P. aeruginosa producing VIM-type MBLs in a lung transplant recipient and the results of the subsequent epidemiological investigation. CASE PRESENTATION: P. aeruginosa isolates collected in the index patient and among patients temporally or spatially linked with the index patient were analyzed in terms of antibiotic susceptibility profile and MBL production. Whole-genome sequencing and phylogenetic reconstruction were also performed for all P. aeruginosa isolates producing VIM-type MBLs. A VIM-producing P. aeruginosa strain was identified in a lung biopsy of a lung transplant recipient with cystic fibrosis. The strain was VIM-1-producer and belonged to the ST308. Despite aggressive treatment, the transplant patient succumbed to the pulmonary infection due to the ST308 strain. A VIM-producing P. aeruginosa strain was also collected from the respiratory samples of a different cystic fibrosis patient attending the same cystic fibrosis center. This isolate harbored the blaVIM-2 gene and belonged to the clone ST175. This patient did not experience an adverse outcome. CONCLUSIONS: This is the first description of a fatal infection due to P. aeruginosa producing VIM-type MBLs in a lung transplant recipient. The circulation of P. aeruginosa isolates harboring MBLs pose a substantial risk to the cystic fibrosis population due to the limited therapeutic options available and their spreading potential.

Plant growth promoting Pseudomonas aeruginosa from Valeriana wallichii displays antagonistic potential against three phytopathogenic fungi.

The soil nature and characterstics are directly related to the micro-organisms present, bio-mineralization process, plant type and thus having harmonius and interdependent relationships. Soil bacteria having antagonistic activity against phytopathogens, play an important role in root growth, overall plant growth and also their composition depends upon the plant species. Population explosion across globe has resulted in indiscriminate use of chemical fertilizers, fungicides and pesticides, thus posing serious risk to plant productivity and soil flora. Plant growth promoting rhizobacteria (PGPRs) are considered safer than chemical fertilizers as they are eco-friendly and sustain longer after colonization in rhizospheric soil. PGPRs are preferred as a green choice and acts as a superior biocontrol agents against phytopathogens. In the present study, a potential rhizobacteria, Pseudomonas aeruginosa (isolate-2) was isolated from the rhizosphere of a medicinal plant, Valeriana wallichi. The bacterial isolate exhibited qualitative tests for plant growth promoting determinatives. It was also subjected to in-vitro biocontrol activity against potential phytopathogens viz. Alternaria alternata, Aspergillus flavus and F. oxysporum. The antagonistic efficacy against F. oxysporum was 56.2% followed by Alternaria alternata to be 51.02%. The maximum inhibition of radial growth of F. oxysporum was 69.2%, Alternaria alternata (46.4%) and Aspergillus flavus (15%). The Pseudomonas aeruginosa exhibited plant growth promotion rhizobacterial activity which can be expoited as biofertilizers. This study deals with microbial revitalization strategy and offers promising solution as a biocontrol agent to enhance crop yield. Further, PGPRs research using the interdisciplinary approaches like biotechnology, nanotechnology etc. will unravel the molecular mechanisms which may be helpful for maximizing its potential in sustainable agriculture.

[Structure of microorganisms isolated from bronhoalveolar lavage from patients in the department of reanimation and intensive therapy.] / Структура микроорганизмов, Ð²Ñ‹Ð´ÐµÐ»ÐµÐ½Ð½Ñ‹Ñ Ð¸Ð· Ð±Ñ€Ð¾Ð½Ñ Ð¾Ð°Ð»ÑŒÐ²ÐµÐ¾Ð»ÑÑ€Ð½Ð¾Ð³Ð¾ лаважа от пациентов отделения реанимации и интенсивной терапии.

The aim of the work was to determine and compare the structure of microorganisms isolated from bronchoalveolar lavage from patients in the ICU of Clinics in 2016 and 2019. This work presents the results of a bacteriological examination of 229 samples from 139 patients for 2016 and 387 samples from 218 patients for 2019. The predominant microorganism in 2016 was Acinetobacter baumanii - 75 (26.2%). Less common were Klebsiella pneumoniae - 55 (19.2%), Pseudomonas aeruginosa - 35 (12.2%), Escherichia coli - 19 (6.6%). In 2019, the prevailing microorganism was K.pneumoniae - 158 (19.1%). As in 2016, A.baumanii - 115 (13.9%) and P. aeruginosa - 57 (6.9%) were most often found, but unlike 2016, in 2019 there was a high incidence of such pathogens as Enterococcus faecalis - 52 (6.3%), Candida albicans - 43 (5.2%), Staphylococcus aureus and Stenotrophomonas maltophilia - 40 (4.8%). One of the features is the presence of polymicrobial associations. In 2016, microorganisms isolated in monoculture predominated (53.4%), while in 2019 the frequency of occurrence of monocultures decreased and amounted to 24.7%. At the same time, a two-component association prevailed (31.5%). Thus, in ICU it is necessary to regularly monitor nosocomial pathogens not only to make the right decision when choosing antimicrobial therapy, but also to identify new potential nosocomial pathogens.

Hypertonic glucose inhibits growth and attenuates virulence factors of multidrug-resistant Pseudomonas aeruginosa.

BACKGROUND: Pseudomonas aeruginosa is the most common Gram-negative pathogen responsible for chronic wound infections, such as diabetic foot infections, and further exacerbates the treatment options and cost of such conditions. Hypertonic glucose, a commonly used prolotherapy solution, can accelerate the proliferation of granulation tissue and improve microcirculation in wounds. However, the action of hypertonic glucose on bacterial pathogens that infect wounds is unclear. In this study, we investigated the inhibitory effects of hypertonic glucose on multidrug-resistant P. aeruginosa strains isolated from diabetic foot infections. Hypertonic glucose represents a novel approach to control chronic wound infections caused by P. aeruginosa. RESULTS: Four multidrug-resistant P. aeruginosa clinical strains isolated from diabetic foot ulcers from a tertiary hospital in China and the reference P. aeruginosa PAO1 strain were studied. Hypertonic glucose significantly inhibited the growth, biofilm formation, and swimming motility of P. aeruginosa clinical strains and PAO1. Furthermore, hypertonic glucose significantly reduced the production of pyocyanin and elastase virulence factors in P. aeruginosa. The expression of major quorum sensing genes (lasI, lasR, rhlI, and rhlR) in P. aeruginosa were all downregulated in response to hypertonic glucose treatment. In a Galleria mellonella larvae infection model, the administration of hypertonic glucose was shown to increase the survival rates of larvae infected by P. aeruginosa strains (3/5). CONCLUSIONS: Hypertonic glucose inhibited the growth, biofilm formation, and swimming motility of P. aeruginosa, as well as reduced the production of virulence factors and quorum sensing gene expression. Further studies that investigate hypertonic glucose therapy should be considered in treating chronic wound infections.

Activity of ceftolozane-tazobactam and comparators when tested against bacterial surveillance isolates collected from patients at risk of infections caused by resistant gram-negative pathogens.

Ceftolozane-tazobactam is an antipseudomonal cephalosporin combined with a ß-lactamase inhibitor. Ceftolozane-tazobactam has been approved for treatment of complicated urinary tract infections and acute pyelonephritis, for complicated intra-abdominal infections (with metronidazole) in adults, and for hospital-acquired bacterial pneumonia including ventilator-associated bacterial pneumonia. This study analyzed gram-negative pathogen susceptibility in US and European patients who are considered at risk for infections caused by pathogens resistant to commonly used antimicrobials: patients in the intensive care unit (ICU), patients on the hematology/oncology or transplant service who may be immunocompromised, and patients >65 years old (yo). ICU patients had the lowest susceptibility for Enterobacterales and PSA. The susceptibility for isolates from the immunocompromised and >65 yo groups was similar. Ceftolozane-tazobactam was the most active agent against PSA, with ≥90%S for >65 yo and immunocompromised, and >80%S for ICU. Meropenem and ceftolozane-tazobactam were the most active agents against Enterobacterales.

Characterization of a new aerosol antibiotic/adjuvant combination for the treatment of P. aeruginosa lung infections.

The lack of novel classes of antibiotics as well as the constant increase of multidrug resistant bacteria are leaving the clinicians disarmed to treat bacterial infections, especially those caused by Gram-negative pathogens. Among all the investigated solutions, the design of adjuvants able to enhance antibiotics activities appears to be one of the most promising. In this context, a polyamino-isoprenyl derivative has been recently identified to be able to potentiate, at a very low concentration the activity of doxycycline against P. aeruginosa bacterial strains by increasing its intracellular concentration. On the other hand, since aerosol therapy allows a rapid drug administration and targets the respiratory system by avoiding the first pass effect and minimizing undesirable systemic effects, we have developed the first adjuvant/antibiotic combination in an aerosolized form and demonstrated the feasibility of such an approach. Thus, combination aerosol droplets have been demonstrated in sizes suitable for inhalation (3.4 and 4.4 µm mass median aerodynamic diameter and 54 and 60% of the aerodynamic particle size distribution less than 5 µm, as measured for the adjuvant NV716 and doxycycline, respectively and with properties (stoichiometric 1:1 ratio of NV716 salt to drug) that would support further development as an inhaled dosage form. Taken together, our results suggest that these molecules could be successfully delivered at the requested concentration in the lungs and then able to decrease drug consumption as well as increase treatment efficacy.

In vitro activity of ceftazidime-avibactam against Gram-negative isolates collected in 18 European countries, 2015-2017.

BACKGROUND: Between 2015-2017, 21 850 Enterobacterales isolates and 6156 Pseudomonas aeruginosa (P. aeruginosa) isolates were collected by 77 centers in 18 European countries as part of the International Network for Optimal Resistance Monitoring (INFORM) study (which was included into the Antimicrobial Testing Leadership and Surveillance [ATLAS] study in 2018). METHODS: A central reference laboratory performed antimicrobial susceptibility testing using broth microdilution panels according to Clinical and Laboratory Standards Institute guidelines. The presence of ß-lactamases was confirmed using multiplex PCR assays. RESULTS: Among Enterobacterales isolates, the highest rates of susceptibility were to ceftazidime-avibactam (99.0%; MIC90 0.5 mg/L), meropenem (96.3%), amikacin (95.2%), and imipenem (92.8%). All Enterobacterales organisms were highly susceptible to colistin (≥ 94.6%), apart from Proteus mirabilis, which is intrinsically resistant to colistin. Susceptibility rates among ceftazidime-resistant isolates were 95.7% for ceftazidime-avibactam and 87.9% for colistin, and 78.5% and 71.1%, respectively, among carbapenemase-positive isolates. Colistin was the only agent with activity against metallo-ß-lactamases (100% susceptibility) among Enterobacterales and P. aeruginosa isolates. Overall susceptibility rates among P. aeruginosa were highest to colistin (99.5%) and ceftazidime-avibactam (92.3%), and were similar to ceftazidime-resistant isolates for colistin (98.9%) and reduced to 66.2% for ceftazidime-avibactam. Susceptibility rates among multidrug-resistant P. aeruginosa isolates were 98.9% to colistin and 71.7% to ceftazidime-avibactam. CONCLUSIONS: Clinical isolates of Enterobacterales and P. aeruginosa collected from Europe, between 2015-2017, were highly susceptible to ceftazidime-avibactam, suggesting it is a useful alternative agent for patients whose treatment options may be limited. Persistent antimicrobial resistance requires continued surveillance and monitoring.