Multidrug-resistant Proteus Mirabilis Research Articles

Prevalence of multidrug-resistant bacterial infections in diabetic foot ulcers: A meta-analysis.

Multidrug-resistant (MDR) bacterial infections have become increasingly common in recent years due to the increased prevalence of diabetic foot ulcers (DFUs). We carried out a meta-analysis aimed at investigating the prevalence of MDR bacteria isolated from DFUs and analysing the risk factors for MDR bacterial infection in patients with DFUs. The PubMed/Medline, Web of Science, Embase, Cochrane Library, Ovid, Scopus, and ProQuest databases were searched for studies published up to November 2023 on the clinical outcomes of MDR bacteria in DFUs. The main outcome was the prevalence of MDR bacteria in DFUs. A total of 21 studies were included, representing 4885 patients from which 2633 MDR bacterial isolates were obtained. The prevalence of MDR bacteria in DFUs was 50.86% (95% confidence interval (CI): 41.92%-59.78%). The prevalence of MDR gram-positive bacteria (GPB) in DFUs was 19.81% (95% CI: 14.35%-25.91%), and the prevalence of MDR gram-negative bacteria (GNB) in DFUs was 32.84% (95% CI: 26.40%-39.62%). MDR Staphylococcus aureus (12.13% (95% CI: 8.79%-15.91%)) and MDR Enterococcus spp. (3.33% (95% CI: 1.92%-5.07%)) were the main MDR-GPB in DFUs. MDR Escherichia coli, MDR Pseudomonas aeruginosa, MDR Enterobacter spp., MDR Klebsiella pneumoniae, and MDR Proteus mirabilis were the main MDR-GNB in DFUs. The prevalence rates were 6.93% (95% CI: 5.15%-8.95%), 6.01% (95% CI: 4.03%-8.33%), 3.59% (95% CI: 0.42%-9.30%), 3.50% (95% CI: 2.31%-4.91%), and 3.27% (95% CI: 1.74%-5.21%), respectively. The clinical variables of diabetic foot ulcer patients infected with MDR bacteria and non-MDR bacteria in the included studies were analysed. The results showed that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization and previous use of antibacterial drugs were significantly different between the MDR bacterial group and the non-MDR bacterial group. We concluded that there is a high prevalence of MDR bacterial infections in DFUs. The prevalence of MDR-GNB was greater than that of MDR-GPB in DFUs. MDR S. aureus was the main MDR-GPB in DFUs, and MDR E. coli was the main MDR-GNB in DFUs. Our study also indicated that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization, and previous use of antibacterial drugs were associated with MDR bacterial infections in patients with DFUs.

Phage P2-71 against multi-drug resistant Proteus mirabilis: isolation, characterization, and non-antibiotic antimicrobial potential.

Proteus mirabilis, a prevalent urinary tract pathogen and formidable biofilm producer, especially in Catheter-Associated Urinary Tract Infection, has seen a worrying rise in multidrug-resistant (MDR) strains. This upsurge calls for innovative approaches in infection control, beyond traditional antibiotics. Our research introduces bacteriophage (phage) therapy as a novel non-antibiotic strategy to combat these drug-resistant infections. We isolated P2-71, a lytic phage derived from canine feces, demonstrating potent activity against MDR P. mirabilis strains. P2-71 showcases a notably brief 10-minute latent period and a significant burst size of 228 particles per infected bacterium, ensuring rapid bacterial clearance. The phage maintains stability over a broad temperature range of 30-50°C and within a pH spectrum of 4-11, highlighting its resilience in various environmental conditions. Our host range assessment solidifies its potential against diverse MDR P. mirabilis strains. Through killing curve analysis, P2-71's effectiveness was validated at various MOI levels against P. mirabilis 37, highlighting its versatility. We extended our research to examine P2-71's stability and bactericidal kinetics in artificial urine, affirming its potential for clinical application. A detailed genomic analysis reveals P2-71's complex genetic makeup, including genes essential for morphogenesis, lysis, and DNA modification, which are crucial for its therapeutic action. This study not only furthers the understanding of phage therapy as a promising non-antibiotic antimicrobial but also underscores its critical role in combating emerging MDR infections in both veterinary and public health contexts.

تأثير دقائق اوكسيد الزنك النانوية المصنعة بايولوجيًا على النمط الظاهري والجيني للغشاء الحيوي لبكتريا Proteus mirabilis

تصنف بكتريا Proteus mirabilis كثالث مسبب لالتهاب المجاري البولية المصاحب لتركيب أنابيب القسطرة البولية. تعد الاغشية الحيوية من عوامل الضراوة اللتي تستعملها البكتريا لمقاومة المضادات الحيوية وفي ضل تطور مقاومة البكتريا للمضادات الحيوية, صار لزامًا على العلماء والباحيثن في مجال الاحياء المجهرية أيجاد بدائل ذات كفائة عالية قادرة على اختراق جدار الخلية البكتيرية وبالتالي قتلها.في السنوات الاخيرة, اكتسبت دقائق النانو المصنعة بايولوجيا والصديقة للبيئة أهتمامًا كبيرًا من قبل الباحثين لأمتلاكها خصائص مميزة كصغر حجمها المتناهي واشكالها المختلفة يمَكنهم من استعمالها كمواد مضادة للبكتيريا في مختلف المجلات الطبية والصحية. تهدف هذه الدراسة الى التحري عن قدرة دقائق اوكسيد النحاس النانوية المصنعة بايولوجيا على تثبيط تكوين الغشاء الحيوي المنتج من قبل بكتيريا Proteus mirabilis. أنتجت هذه الدقائق بأستعمال راشح بكتيري يحتوي على الانزيمات المختزلة لملح النحاس واستخدمت عدة تقنيات لتحديد الصفات الفيزيائية المظهرية لدقائق النانو المنتجة حيث استخدمت تقنية XRD لتأكيد التركيب خماسي الشكل لهذه الدقائق , بينما استعملت تقنية TEM لتحديد قطر الجزيئات المنتجة بمعدل 84.45 نانومتر. اما FESEM فقد تم استخدامه لتحديد الصفات الخارجية لسطح جزيئات النانو المنتجة , تم تأكيد النتائج بأستخدام تقنية AFM للكشف عن توزيع و وعورة جزيئات النانو.اما UV فقد سجلت ااقصى امتصاصية على الطول الموجي nm287 .تم التحري في هذه الدراسة عن فعالية دقائق اوكسيد النحاس النانوية في منع تكون الغشاء الحيوي حيث أستعمل مستحلب دقائق اوكسيد النحاس النانوي بالتركيز تحت القاتل 32 μg/ml . سجلت نتائج هذه الدراسة انخفاضا ملحوضَا في انتاج الغشاء الحيوي للبكتريا المنتجه له حيث سجلت العزلات ذات الانتاجية العالية للغشاء الحيوي ضعفأ في الانتاج بعد معاملتها بالتركيز المستعمل من دقائق اوكسيد النحاس النانوية. جاء تأثير هذه الدقائق على كل من النمط الظاهري والتعبير الجيني لجين LuxS المسؤول عن تكوين الغشاء الحيوي بأستخدام تقنية rtPCRحيث سجلت الدراسة انخفاضا في التعبير الجيني لهذا الجين بعد معاملة سلالات البكتريا قيد الدراسة بدقائق اوكسيد النحاس النانوية مقارنتاً بالعزلات غير المعاملة. من خلال نتائج هذه التجربة يمكن التوصل الى امكانية اعتماد دقائق اوكسيد الزنك النانوية كعامل مضاد للبكتيريا عن استخدامه بالتركيز المناسب.

Green-Synthesized Silver Nanoparticles in the Prevention of Multidrug-Resistant Proteus mirabilis Infection and Incrustation of Urinary Catheters BioAgNPs Against P. mirabilis Infection.

This study aimed to assess the activity of AgNPs biosynthesized by Fusarium oxysporum (bio-AgNPs) against multidrug-resistant uropathogenic Proteus mirabilis, and to assess the antibacterial activity of catheters coated with bio-AgNPs. Broth microdilution and time-kill kinetics assays were used to determine the antibacterial activity of bio-AgNPs. Catheters were coated with two (2C) and three (3C) bio-AgNPs layers using polydopamine as crosslinker. Catheters were challenged with urine inoculated with P. mirabilis to assess the anti-incrustation activity. MIC was found to be 62.5µmoll-1, causing total loss of viability after 4h and bio-AgNPs inhibited biofilm formation by 76.4%. Catheters 2C and 3C avoided incrustation for 13 and 20days, respectively, and reduced biofilm formation by more than 98%, while the pristine catheter was encrusted on the first day. These results provide evidence for the use of bio-AgNPs as a potential alternative to combat of multidrug-resistant P. mirabilis infections.

Multidrug-Resistant Proteus mirabilis Infections and Clinical Outcome at Tertiary Hospital in Riyadh, Saudi Arabia.

Proteus mirabilis (P. mirabilis) is known to cause various infections, most commonly urinary tract infections, and is a threat to hospitalized patients, especially in long-stay departments that utilize invasive devices. This study aims to fill the knowledge gap regarding P. mirabilis epidemiology and antimicrobial resistance in Saudi Arabia. It investigates epidemiological patterns, resistance characteristics, and clinical outcomes among P. mirabilis patients at King Fahad Medical City in Riyadh from 2019 to 2021. A total of 598 P. mirabilis isolated from diverse clinical specimens, including the clinical information of 78 intensive care unit (ICU) patients, were included in the current study. The Phoenix BD instrument was used for complete identification and sensitivity testing of Proteus spp. Demographic, clinical, and outcome data were reported and compared using statistical analysis. Pan-drug-resistant isolates wereidentified in 2019 (n = 6), although multi- and extensively drug-resistant isolate frequencies were greatest among all patients in 2019. The highest susceptibility levels were observed for piperacillin-tazobactam, carbapenems, and cephalosporins antibiotics. In contrast, Cephalothin, trimethoprim-sulfamethoxazole, and ampicillin had the lowest susceptibilities. Urine infections with a positive culture of P. mirabilis were significantly higher in females and non-ICU patients (p <0.001), but respiratory infections were significantly higher in ICU patients (p <0.001). Moreover, ICU patients infected with P. mirabilis and undergoing renal dialysis have a 7.2-fold (P 0.034) higher risk of death than those not receiving dialysis. Hospitalized patients are at risk of fatal consequences due to P. mirabilis infection. It is crucial to conduct further investigation to fully understand the severity of this issue and take necessary measures to prevent it.

Inhibitory Effects of Biosynthesized Copper Nanoparticles on Biofilm Formation of Proteus mirabilis

This study aimed to explore whether green synthesized copper nanoparticles (CuNPs) can function as an anti-biofilm agent produced by P. mirabilis. The nanoparticles were synthesized from cells free extract of P. mirabilis. Characterization of biosynthesized copper nanoparticles was carried out to determine the chemical and physical properties of the product using atomic-force microscopy (AFM), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) and UV-visible spectroscopy. The hexagonal structure was confirmed by XRD, size range was marked 13-19nm by TEM. FESEM was used to confirm the surface morphology. AFM analysis was used to reveal the roughness and distribution of nanoparticles. UV–visible spectra of the synthesized nanoparticles recorded a maximum peak at 380 nm. Copper nanoparticles showed remarkable biofilm inhibitory effects on wild type strains of multidrug resistant Proteus mirabilis. After incubation for 24 and 48 hours at 37oC with 128 μg/ml sub minimum inhibitory concentration (MIC) of CuO nanoparticles, strong biofilm producer strains showed weak biofilm production. Down regulation changes in LuxS expression using real time PCR technology were detected after treatment with copper nanoparticles of these strains.

The expression of the fosfomycin (fos) resistant gene in chitosan nanoparticle-treated Proteus mirabilis isolated from urine samples

The emergence of multidrug-resistant Proteus mirabilis is a significant threat to public health due to the high morbidity and mortality associated with catheter-associated urinary tract infections. The clinical treatment options for these infections are becoming less effective, emphasizing the need for alternative antibacterial agents. Chitosan nanoparticles (CS-NPs) have demonstrated antimicrobial activity against a wide range of pathogens. Hence, this study aimed to detect fosfomycin resistance gene in P. mirabilis isolates collected from urine samples, also to study the impact of CS-NPs on the fosA gene expression in P. mirabilis using real-time PCR method. In this cross-sectional descriptive study, 60 strains of P. mirabilis were collected from urine samples. Antibiotic susceptibility tests against nine antibiotics were performed using disk diffusion method. Moreover, multiplex PCR test was performed to investigate the presence of fosA, fosB and fosC genes. Afterwards, MIC of CS-NPs against P. mirablis isolates was determined by microbroth dilution method. Real-time PCR was performed to investigate the expression fosA in isolates treated with sub-MIC concentrations of CS-NPs. Our results showed that ciprofloxacin had the lowest rate of resistance at 15 %, while 48.3 % of the isolates were resistant to fosfomycin. The frequency of the fosA, fosB, and fosC genes were 23.3 %, 8.3 %, and 11.7 %, respectively. The MIC of the synthesized nanoparticle was 500 μg/mL, with a sub-MIC concentration of 250 μg/mL. Treatment with the sub-MIC concentration of the nanoparticle resulted in a statistically significant reduction in the expression level of the fosA gene 0.562 (1.78 downregulation compared to control). The study suggests concerning increase in antibiotic resistance among P. mirabilis isolates. CS-NPs demonstrated effective antimicrobial properties, as evidenced by their ability to reduce the expression of the fosfomycin resistance gene. This suggests that CS-NPs may be a promising option for the treatment of infections caused by Proteus. However, further research is needed to fully evaluate their efficacy and safety.

Genetic analysis of resistance and virulence characteristics of clinical multidrug-resistant Proteus mirabilis isolates.

Proteus mirabilis is the one of most important pathogens of catheter-associated urinary tract infections. The emergence of multidrug-resistant (MDR) P. mirabilis severely limits antibiotic treatments, which poses a public health risk. This study aims to investigate the resistance characteristics and virulence potential for a collection of P. mirabilis clinical isolates. Antibiotic susceptibility testing revealed fourteen MDR strains, which showed high resistance to most β-lactams and trimethoprim/sulfamethoxazole, and a lesser extent to quinolones. All the MDR strains were sensitive to carbapenems (except imipenem), ceftazidime, and amikacin, and most of them were also sensitive to aminoglycosides. The obtained MDR isolates were sequenced using an Illumina HiSeq. The core genome-based phylogenetic tree reveals the high genetic diversity of these MDR P. mirabilis isolates and highlights the possibility of clonal spread of them across China. Mobile genetic elements SXT/R391 ICEs were commonly (10/14) detected in these MDR P. mirabilis strains, whereas the presence of resistance island PmGRI1 and plasmid was sporadic. All ICEs except for ICEPmiChn31006 carried abundant antimicrobial resistance genes (ARGs) in the HS4 region, including the extended-spectrum β-lactamase (ESBL) gene blaCTX-M-65. ICEPmiChn31006 contained the sole ARG blaCMY-2 and was nearly identical to the global epidemic ICEPmiJpn1. The findings highlight the important roles of ICEs in mediating the spread of ARGs in P. mirabilis strains. Additionally, these MDR P. mirabilis strains have great virulence potential as they exhibited significant virulence-related phenotypes including strong crystalline biofilm, hemolysis, urease production, and robust swarming motility, and harbored abundant virulence genes. In conclusion, the prevalence of MDR P. mirabilis with high virulence potential poses an urgent threat to public health. Intensive monitoring is needed to reduce the incidence of infections by MDR P. mirabilis.

Synthesis and photodynamic antimicrobial chemotherapy against multi-drug resistant Proteus mirabilis of ornithine-porphyrin conjugates in vitro and in vivo.

For the treatment of bacterial infections, photodynamic antimicrobial chemotherapy (PACT) has the advantage of circumventing multi-drug resistance. In this work, new cationic photosensitizers against multi-drug resistant Proteus mirabilis (MRPM) were designed and synthesized by the conjugation of amino phenyl porphyrin with basic amino acid L-ornithine. Their photoinactivation efficacies against MRPM in vitro were reported and include the influence of laser energy, uptake, MIC and MBC, dose-dependent photoinactivation effects, membrane integrity, and fluorescence imaging. The PACT in vivo was evaluated using a wound mouse model infected by MRPM. Photosensitizer 4d displayed high photo inactivation efficacy against MRPM at 7.81 μM under illumination, and it could accelerate wound healing via bactericidal effect. These ornithine-porphyrin conjugates are potential photosensitizers for PACT in the treatment of MRPM infection.

Epidemic characteristics of the SXT/R391 integrated conjugative elements in multidrug-resistant Proteus mirabilis isolated from chicken farm

This study was designed to depict prevalence and antimicrobial resistance characteristics of Proteus mirabilis (P. mirabilis) strains in 4 chicken farms and to probe the transfer mechanism of resistance genes. A total of 187 P. mirabilis isolates were isolated from 4 chicken farms. The susceptibility testing of these isolates to 14 antimicrobials showed that the multidrug resistance (MDR) rate was as high as 100%. The β-lactamase resistance genes blaOXA-1, blaCTX-M-1G, blaCTX-M-9G and colistin resistance gene mcr-1 were highly carried in the P. mirabilis isolates. An MDR strain W47 was selected for whole genome sequencing (WGS) and conjugation experiment. The results showed that W47 carried 23 resistance genes and 64 virulence genes, and an SXT/R391 integrated conjugative elements (ICEs) named ICEPmiChn5 carrying 17 genes was identified in chromosome. ICEPmiChn5 was able to be excised from the chromosome of W47 forming a circular intermediate, but repeated conjugation experiments were unsuccessful. Among 187 P. mirabilis isolates, 144 (77.01%, 144/187) isolates carried ICEPmiChn5-like ICEs, suggesting that ICEs may be the major vector for the transmission of resistance genes among MDR chicken P. mirabilis strains in this study. The findings were conducive to insight into the resistance mechanism of chicken P. mirabilis strains and provide a theoretical basis for the use of antibiotics for the treatment of MDR P. mirabilis infections in veterinary clinic.

Whole genome sequencing of multidrug-resistant Proteus mirabilis strain PM1162 recovered from a urinary tract infection in China

Proteus mirabilis is an important opportunistic Gram-negative pathogen. This study reports the whole genome sequence of multidrug-resistant (MDR) P. mirabilis PM1162 and explores its antibiotic resistance genes (ARGs) and their genetic environments. P. mirabilis PM1162 was isolated from a urinary tract infection in China. Antimicrobial susceptibility was determined, and whole genome sequencing (WGS) was performed. ARGs, insertion sequence (IS) elements, and prophages were identified using ResFinder, ISfinder, and PHASTER software, respectively. Sequence comparisons and map generation were performed using BLAST and Easyfig, respectively. On its chromosome, P. mirabilis PM1162 harboured 15 ARGs, including cat, tet(J), blaCTX-M-14 (three copies), aph(3')-Ia, qnrB4, blaDHA-1, qacE, sul1, armA, msr(E), mph(E), aadA1, and dfrA1. We focused our analysis on the four related MDR regions: (1) genetic contexts associated with blaCTX-M-14; (2) the prophage containing blaDHA-1, qnrB4, and aph(3')-Ia; (3) genetic environments associated with mph(E), msr(E), armA, sul, and qacE; and (4) the class II integron harbouring dfrA1, sat2, and aadA1. This study reported the whole genome sequence of MDR P. mirabilis PM1162 and the genetic context of its ARGs. This comprehensive genomic analysis of MDR P. mirabilis PM1162 provides a deeper understanding of its MDR mechanism and elucidates the horizontal spread of its ARGs, thus providing a basis for the containment and treatment of the bacteria.

Prevalence pattern of multidrug resistant Proteus mirabilis recovered from wound of human and cats in Wasit governorate

The current work was conducted for isolation and identification of Proteus mirabilis from humans and cats. A total of one hundred and fifty samples were collected from hospitals of wasit city during the period from 23/7/2021 to 13/1/2022. These clinical samples included: (90) wound swabs from humans While the total number of samples amount to wound swabs in cats (60). These samples of humans were collected from Al- Zahra Teaching Hospital in wasit and the samples of cats is collected from different places. All isolates Proteus mirabilis were characterized according to the morphology and microscopic characteristics, along with the biochemical and confirmatory APi 20 E tests. These isolates were obtained from: humans (15) and cats (11).Then determination of antibiotics susceptibility pattern of recovered isolates. The human isolates showed resistant 100 % to Ampicillin, Penicillin, Trimethoprim-Sulfamethoxazole, Streptomycin, Chloramphenicol, Amoxicillin / clavulanic acid, Erythromycin, Tetracycline, Cefoxitin and Vancomycin. Sensitive (100%) for Gentamycin and Ofloxacin. otherwise the cat’s isolates showed resistant (100%) to Ampicillin, Penicillin, Trimethoprim-Sulfamethoxazole, Streptomycin, Chloramphenicol, Amoxicillin / clavulanic acid, Erythromycin, Tetracycline, Ofloxacin, Cefoxitin and Vancomycin. Sensitive (100%) for Gentamycin only.

Nosocomial Outbreak of Carbapenemase-Producing Proteus mirabilis With Two Novel Salmonella Genomic Island 1 Variants Carrying Different bla NDM-1 Gene Copies in China.

NDM-1-producing multidrug-resistant Proteus mirabilis brings formidable clinical challenges. We report a nosocomial outbreak of carbapenem-resistant P. mirabilis in China. Six P. mirabilis strains collected in the same ward showed close phylogenetic relatedness, indicating clonal expansion. Illumina and MinION sequencing revealed that three isolates harbored a novel Salmonella genomic island 1 carrying a blaNDM–1 gene (SGI1-1NDM), while three other isolates showed elevated carbapenem resistance and carried a similar SGI1 but with two blaNDM–1 gene copies (SGI1-2NDM). Four new single nucleotide mutations were present in the genomes of the two-blaNDM–1-harboring isolates, indicating later emergence of the SGI1-2NDM structure. Passage experiments indicated that both SGI variants were stably persistent in this clone without blaNDM–1 copy number changes. This study characterizes two novel blaNDM–1-harboring SGI1 variants in P. mirabilis and provides a new insight into resistance gene copy number variation in bacteria.

Prevalence and characteristics of multidrug-resistant Proteus mirabilis from broiler farms in Shandong Province, China

Animal-derived Proteus mirabilis (P. mirabilis) is an important food-borne zoonotic bacillus and widely exists in the broiler-breeding industry. The present study was designed to explore the P. mirabilis prevalence and antimicrobial resistance characteristics in 6 conventional broiler-fattening farms in Shandong Province, China. The overall isolation rate of P. mirabilis was 7.07% (50/707). Antimicrobial resistance was very common in the P. mirabilis isolated from these farms and varied for different antibacterial drugs, with chloramphenicol, ciprofloxacin, and trimethoprim-sulfamethoxazole having the highest resistance rate (98%) and aztreonam the lowest (0%). Multidrug resistance was as high as 100%. The majority of the MDR isolates were resistant to between 9 and 12 of the antibiotics, with these accounting for 76% (38/50) of multidrug resistant strains. These P. mirabilis isolates carried 24 drug-resistance genes in 6 types, with stcM having the highest rate (96%) and cmlA, blaTEM, and qnrC the lowest (2%). Superdrug resistance gene blaNDM-1 was found in 10% (5/50) of isolates from poultry farms in Shandong. All the P. mirabilis isolates carried at least 6 virulence genes, with 100% detection rates of the ireA and hpmA genes. Our study revealed that the P. mirabilis strains isolated in the Shandong area all showed the MDR phenotype and the poultry-derived carbapenem-resistant MDR P. mirabilis strains may pose a potential risk to humans. Surveillance findings presented herein will be conducive to our understanding of the prevalence and characteristics of carbapenem-resistant P. mirabilis strains in Shandong, China.

Purple urine bag syndrome - a sign of urinary tract infection, or just of urinary catheter bacterial colonization: A case report

Introduction. Purple urine bag syndrome is a condition where the urinary catheter bag turns purple as a result of the interaction between bacteria, urine and components of the urine bag. It appears in a certain group of patients with the following risk factors: urinary tract infection, older age, long-term indwelling urinary catheter, constipation, chronic kidney disease. Case Report. Two patients with purple urine bag syndrome are presented. The first patient, a 66-year-old man, was hospitalized due to decompensation of alcoholic liver cirrhosis. A urinary catheter was placed on admission, and on the fourteenth day of hospitalization, a purple discoloration of the urine in the urinary bag was noticed. Multidrug-resistant Proteus mirabilis and Enterococcus faecalis were isolated by microbiological analysis of urine. The second patient was a 92-year-old man, hospitalized for acute gastrointestinal bleeding in the form of hematochezia, with an indwelling urinary catheter and a history of a prostate cancer surgery. On the third hospital day, a purple content in the urinary catheter bag was detected and Klebsiella pneumoniae and Morganella morganii were confirmed by bacteriological analysis. Both patients were without clinical and laboratory signs of acute infection. In both cases, the urinary catheter was replaced and ceftriaxone was administered empirically. Conclusion. Current guidelines for purple urine bag syndrome recommend catheter replacement and empiric antibiotic therapy. In clinical practice, it is necessary to emphasize that urine sampling for bacteriological analysis is performed only after replacing the catheter, in order to establish the exact etiology of the syndrome and radical use of antibiotics.

Characterization of NDM-1-Producing Carbapenemase in Proteus mirabilis among Broilers in China.

Carbapenem-resistant pathogens mediated by metallo-beta-lactamases (MBLs) have spread worldwide, where NDM-1 is a typical and key MBL. Here, we firstly discussed the distribution characterization of NDM-1, which produces multidrug-resistant Proteus mirabilis among broilers in China. From January to April 2019, 40 (18.1%, 40/221) blaNDM-1-carrying P. mirabilis strains were recovered from commercial broilers in slaughterhouse B in China. All the isolates were resistant to imipenem, meropenem and other β-lactams. These isolates belong to five clusters identified via pulsed field gel electrophoresis (PFGE). Further studies on twenty representative strains revealed that seven blaNDM-1 genes were located on plasmids with sizes of 104.5–138.9 kb. Notably, only three strains (PB72, PB96 and PB109) were successfully transferred to Escherichia coli J53, while the other four isolates were located in nontransferable plasmids. The rest were harbored in chromosomes. Ulteriorly, based on whole genome sequencing (WGS), these twenty isolates showed four typical phylogenetic clades according to single nucleotide polymorphisms (SNPs) of a core genome and presented four main genomic backbone profiles, in which type II/III strains shared a similar genetic context. All of the above is evidence of blaNDM-1 transmission and evolution in P. mirabilis, suggesting that the prevalence may be more diverse in broiler farms. Accordingly, as intestinal and environmental symbiotic pathogens, blaNDM-1-positive P. mirabilis will pose greater threats to the environment and public health.

Efficacy of three lytic bacteriophages for eradicating biofilms of multidrug-resistant Proteus mirabilis.

Proteus mirabilis is one of the most frequent causes of catheter-associated urinary tract infections (CAUTIs) owing to its capability to colonize and develop crystalline multidrug-resistant (MDR) biofilms. Here, we report the isolation and partial characterization of three novel bacteriophages, vB_PmiM-ES1a, vB_PmiM-ES1b, and vB_PmiM-ES1c, which were active against the planktonic form and biofilms of the MDR P. mirabilis strain ES01, isolated from CAUTIs in Egypt. The antibiotic susceptibility profile of the P. mirabilis isolates showed resistance to most of the antibiotics tested. The isolated phages were identified morphologically using TEM, and each appeared to have myovirus-like morphology. The three phages displayed strong lytic activity and a narrow host range, and they were stable at different ranges of temperatures and pH values. One-step growth kinetics showed a lysis time of 180 min with a burst size of 99.6, 95, and 86 PFU/cell for phage vB_PmiM-ES1a, vB_PmiM-ES1b, and vB_PmiM-ES1c, respectively. The three phages exhibited different digestion patterns using different restriction enzymes. The genome size was estimated to be 59.39 kb, 62.19 kb, and 52.07 kb for phage vB_PmiM-ES1a, vB_PmiM-ES1b, and vB_PmiM-ES1c, respectively. A phage cocktail including the three phages showed a potential ability to reduce and eradicate a biofilm formed by the MDR Proteus mirabilis EG-ES1. Accordingly, a phage cocktail of vB_PmiM-ES1a, vB_PmiM-ES1b, and vB_PmiM-ES1c is considered a promising candidate for use as a biocontrol agent against MDR Proteus mirabilis bacteria.

In Vitro and In Vivo Evaluation of Antibiotic Combinations against Multidrug Resistant Proteus Mirabilis Isolated from Admitted Patients of Dhaka Medical College Hospital, Dhaka

Emergence of MDR P. mirabilis is a threat for high morbidity and mortality with catheter-associated urinary tract infections leading to urolithiasis and permanent renal damage, bacteremia and sepsis. Global shortage of new effective antibiotic with reduced susceptibility of P. mirabilis to imipenem, tigecycline and resistance to colistin needs antimicrobial combinations. So, different antimicrobial combinations were used to see their efficacy both in vitro and in vivo with their resistance in Bangladesh. MIC of antibiotics alone and in combination and efficacies of different antibiotic combinations in vivo (mice model) were evaluated. PCR and sequencing of resistance genes were done. Among the 500 samples, 70% were culture positive and out of these, 10.57% were P. mirabilis. Among isolated P. mirabilis, 24.32%, 21.62%, 27.03% and 78.38% were resistant to fosfomycin, imipenem, tigecycline and amikacin respectively and 75.68%, 13.51% and 10.81% were MDR, XDR and PDR respectively. Among fosfomycin resistant P. mirabilis, 77.78%, 44.44% and 22.22% were positive for fosA, fosA3 and fosA4 respectively. Among imipenem resistant P. mirabilis, 62.50% were positive for NDM-1 and OXA-10, 50% for NDM-2, OXA-23 and OXA-48, 25% for OXA-58. In vitro combination of imipenem-amikacin and imipenem-fosfomycin showed 100%, and 75% synergism respectively. The best in vivo results appeared in the group treated with imipenem-amikacin and imipenem-fosfomycin combinations where 100% bacterial clearance was observed. As P. mirabilis showed high level resistance towards commonly used antimicrobial agents, it is very difficult to treat by a single agent. So, emphasis should be given on using antibiotic combinations.

A rare case on Rheumatic Heart Disease with Urosepsis and Septic shock

Rheumatic heart disease(RHD) is an inflammatory disease that mostly occurs in children of 5-15 years old. The major complications of RHD include arrhythmias, especially atrial fibrillation, stroke, infective endocarditis, cardiac failure, and also noted that problems increased in pregnancy. This is a rare case of RHD and urosepsis in a 67- year- old patient with a known history of cerebrovascular accident, pulmonary Arteriovenous(AV) malformation, acute renal failure, and hyponatremia presented to the emergency department with complaints of fever, severe breathlessness, and cough. The patient initially showed clinical manifestations of elevated inflammatory markers, neutrophilic leucocytosis, and hyponatremia, indicating septic shock. Our patient had been empirically treated with Piperacillin-Tazobactam because of the clinical features of urosepsis with septic shock. Based on Bronchoalveolar lavage(BAL) culture with non-fermenter Presumptive Acinetobacter and Klebsiella species and culture sensitivity report antibiotics were changed to Colistin and meropenem. The presence of carbapenem-resistant Klebsiella pneumoniae (CR Kp) entails stopping meropenem and adding tigecycline. Further creatinine clearance declined, and the drug Colistin was changed to Polymixin B. Meropenem was readministered based on the culture reports with scanty growth of multidrug-resistant Proteus mirabilis. Rational use of antibiotics along with the appropriate supportive measures is a meaningful measure in treating a rare and complicated condition of RHD with urosepsis.

Clonal outbreak caused by VIM-4-producing Proteus mirabilis in a Greek tertiary-care hospital

Carbapenem-resistant Enterobacterales have become a major public-health issue worldwide. Here we report an outbreak caused by a clonal multidrug-resistant Proteus mirabilis strain producing VIM-4 metallo-β-lactamase (MBL) and TEM-2 β-lactamase in a Greek tertiary-care hospital. From July 2015 to February 2016, 27 imipenem-resistant P. mirabilis isolates were recovered from 14 patients hospitalised in two intensive care units (ICUs) and the internal medicine department in AHEPA University Hospital, Thessaloniki. The isolates were either susceptible or resistant to meropenem and were resistant to all remaining β-lactams except aztreonam. Phenotypic and molecular analysis revealed that all of the isolates harboured a blaVIM-4 MBL gene. Resistome analysis of a representative isolate showed the presence of an IncQ1 plasmid harbouring the blaVIM-4 carbapenemase and blaTEM-2 β-lactamase genes among resistance genes coding for resistance to β-lactams, aminoglycosides, trimethoprim, sulfonamides and lincosamides. Genotyping by pulsed-field electrophoresis (PFGE) revealed that the isolates were epidemiologically related. After recovery of the index carbapenemase-producing P. mirabilis clinical isolate, infection control measures were intensified in the affected departments. Rectal sampling for carbapenem-resistant bacteria was initiated on a weekly basis among patients admitted to the general ICU. The outbreak was finally interrupted 6 months later in February 2016. This is the first documentation of the blaVIM-4 MBL gene in P. mirabilis as well as the first hospital outbreak caused by a MBL-producing P. mirabilis strain.