XDR Phenotype Research Articles

Colistin, doxycycline and Labetalol-meropenem combination are the most active against XDR-Carbapenem-resistant Acinetobacter baumannii: role of a novel transferrable plasmid conferring carbapenem resistance

This study aimed to evaluate the antimicrobial susceptibility and combination of a beta-blocker, labetalol (LAB) and meropenem (MEM) on Carbapenem-resistant (CR) A. baumannii clinical isolates. A total of 43 CR- A. baumannii were isolated of which 37 (86.6%) and 28 (65%) exhibited MDR and XDR phenotypes, respectively. Colistin and doxycycline still retain their activities in 93.1% and 72.1% of the isolates, respectively. Combining MEM with LAB at 0.25 mg /mL, decreased MIC values in 91.4% (32/35) however, at 0.5 mg /mL, it decreased MIC value and restored susceptibility to MEM in 100% and 91.4% of the tested isolates, respectively. A novel transferable plasmid pAcbGIM3 harboring aph-3’, blaoxa-58,blaGIM3 and blaCTX-M3 and eight mobile genetic elements were successfully isolated from a pan-drug resistant (PDR) isolate. In conclusion, LAB-MEM is a promising combination and should be clinically examined. This is the first report of a transmissible plasmid harboring blaGIM3 gene in Egypt.

Phenotypic Investigation and Detection of Biofilm-Associated Genes in Acinetobacter baumannii Isolates, Obtained from Companion Animals.

Bacteria of the genus Acinetobacter, especially Acinetobacter baumannii (Ab), have emerged as pathogens of companion animals during the last two decades and are commonly associated with hospitalization and multidrug resistance. A critical factor for the distribution of relevant strains in healthcare facilities, including veterinary facilities, is their adherence to both biotic and abiotic surfaces and the production of biofilms. A group of 41 A. baumannii isolates obtained from canine and feline clinical samples in Greece was subjected to phenotypic investigation of their ability to produce biofilms using the tissue culture plate (TCP) method. All of them (100%) produced biofilms, while 23 isolates (56.1%) were classified as strong producers, 11 (26.8%) as moderate producers, and 7 (17.1%) as weak producers. A correlation between the MDR and XDR phenotypes and weak or moderate biofilm production was identified. Moreover, the presence of four biofilm-associated genes bap, blaPER, ompA, and csuE was examined by PCR, and they were detected in 100%, 65.9%, 97.6%, and 95.1% of the strains respectively. All isolates carried at least two of the investigated genes, whereas most of the strong biofilm producers carried all four genes. In conclusion, the spread and persistence of biofilm-producing Ab strains in veterinary facilities is a matter of concern, since they are regularly obtained from infected animals, indicating their potential as challenging pathogens for veterinarians due to multidrug resistance and tolerance in conventional eradication measures. Furthermore, considering that companion animals can act as reservoirs of relevant strains, public health concerns emerge.

Monitoring of Klebsiella pneumoniae as one of the criteria of microecological characterization of a water body

Introduction. Representatives of the family Enterobacteriaceae are ubiquitous in the environment, causing severe, including opportunistic diseases in immunocompromised individuals. The occurrence of antibiotic-sensitive bacteria of the Klebsiella genus within the recreational zone of a water body is potent of posing an epidemiologic danger to the inhabitants of the settlement. 
 Materials and Methods. Water samples from the surface aquifers of the Don and Temernik rivers of Rostov-on-Don served as the material for the study. The sensitivity of isolates of Kl. pneumoniae isolates to fourteen antibacterial preparations were investigated by disk-diffusion method in accordance with the requirements of MUK 4.2.1980-04 and EUCAST v. 13.0 (2023). 13.0 (2023). Carbapenemase genes VIM, IMP, NDM, KPC, OXA-48, NDM were determined using commercial diagnostic kits AmpliSense MDR MBL-FL, AmpliSense MDR KPC/OXA-48-FL, AmpliSense MDR Ab-OXA-FL.
 Results. In 2022, 247 isolates of Klebsiella pneumoniae were isolated in 14 biotopes of water bodies of Rostov-on-Don. Biotopes of epidemiological significance were identified with the presence of antibiotic resistance genes in 28 isolates isolated above and below the sewage discharge site (sampling point #1 and #5) and strains isolated from the mouth of the Temernik River (sampling point #14). Phenotype of multidrug-resistant (MDR) in point No. 1 possessed 22%, point No. 5 – 26.9%, point No. 14 – 26%; phenotype of extreme drug resistance (XDR) in point No. 1 possessed 11.1 %, point No. 5 – 15.3%, point No. 14 – 13%; phenotype of pan-drug-resistant (PDR) in point No. 1 did not possess, point No. 5 – 3.8%, point No. 14 – 4.3%.
 Limitations. A limitation of the study is related to the location of water sampling from the river. Don and R. Temernik on the territory of Rostov-on-Don, covering from March to November 2022. In this article, we limited ourselves to sanitary-bacteriological and molecular genetic analysis.
 Conclusion. The detection of PDR, XDR, and MDR antibiotic-resistant phenotypes of Klebsiella pneumoniae, as well as the detection of resistance genes, indicates to an increased risk of water-associated acute intestinal infections, especially in immunosuppressed individuals.

Enterobacter asburiae ST229: an emerging carbapenemases producer

Enterobacter asburiae, member of the Enterobacter cloacae complex (ECC) group, shows an increasing clinical relevance being responsible for infections like pneumonia, urinary tract infections and septicemia. The aim of the present study was the investigation of the genomic features of two XDR E. asburiae ST229 clinical strains co-carrying blaNDM-1 and blaVIM-1 determinants, collected in October 2021 and in June 2022, respectively. Two E. asburiae strains were collected from rectal swabs of as many patients admitted to the cardiopulmonary intensive care unit of Fondazione I.R.C.C.S. “Policlinico San Matteo” in Pavia, Italy. Based on the antibiotic susceptibility profile results, both isolates showed an XDR phenotype, retaining susceptibility only to fluoroquinolones. Both isolates shared identical resistome, virulome, plasmid content, and belonged to ST229, a rarely reported sequence type. They co-harbored blaNDM-1 and blaVIM-1 genes, that resulted located on transferable plasmids by conjugation and transformation. Moreover, both strains differed in 24 SNPs and showed genetic relatedness with E. asburiae ST709 and ST27. We described the first case of ST229 E. asburiae co-harboring blaNDM-1 and blaVIM-1 in Italy. This study points out the emergence of carbapenemases in low-risk pathogens, representing a novel challenge for public health, that should include such types of strains in dedicated surveillance programs. Antimicrobial susceptibility testing was carried out using Thermo Scientific™ Sensititre™ Gram Negative MIC Plates DKMGN. Both strains underwent whole-genome sequencing (WGS) using Illumina Miseq platform. Resistome, plasmidome, virulome, MLST, plasmid MLST and a SNPs-based phylogenetic tree were in silico determined.

On the onset and dispersal of a major MDR TB clone among HIV-negative patients, Tunisia

BackgroundTo carry out a whole genome sequencing (WGS)-based investigation on the emergence and spread of the largest multidrug-resistant tuberculosis (MDR TB) outbreak that has been thriving among HIV-negative patients, Tunisia, since the early 2000s.MethodsWe performed phylogeographic analyses and molecular dating based on a WGS dataset representing 68 unique Mycobacterium tuberculosis isolates, covering almost the entire MDR TB outbreak for the time period 2001–2016.ResultsThe data indicate that the ancestor of the MDR TB outbreak emerged in the region of Bizerte, as early as 1974 (95% CI 1951–1985), from where it spread to other regions by 1992 (95% CI 1980–1996). Analysis of a minimum spanning tree based on core genome Multilocus Sequence Typing (cgMLST) uncovered the early spill-over of the fitness-compensated MDR TB strain from the prison into the general population. Indeed, cases with history of incarceration were found to be directly or indirectly linked to up to 22 new outbreak cases (32.35%) among the non-imprisoned population. By around 2008, the MDR TB outbreak strain had acquired additional resistance, leading to an XDR phenotype.ConclusionsWGS allowed refining our understanding of the emergence and evolution of the largest MDR TB outbreak in Tunisia, whose causative strain has been circulating silently for almost 26 years before. Our study lends further support to the critical role of prisons-related cases in the early spread of the outbreak among the general population. The shift to an XDR phenotype of such an epidemic clone prompts an urgent need to undertake drastic control measures.

Uropatógenos multirresistentes y con resistencia extendida a los antimicrobianos aislados en pacientes adultos de la comunidad de Barinas, Venezuela.

This study aimed to determine the frequency of multidrug-resis-tant (MDR) and extensively drug-resistant (XDR) uropathogens isolated from adult patients in Barinas City, Venezuela, in 2022. Of 1019 urine cultures from patients who attended the Barinas Clinical Microbiological Laboratory, 337 (33.07%) were selected according to inclusion criteria. The microbiological processing of urine was carried out through conventional methods. Antimicro-bial susceptibility tests and extended-spectrum beta-lactamase determination were performed using standardized phenotypic methods. The classification of MDR and XDR strains was conducted according to international criteria. Data were processed through descriptive statistics and frequency analysis. Of 337 urine cultures analyzed, 70.92% corresponded to female patients, and the age groups between 31 and 60 years were the most frequent. Of the uropathogens identified, 93.17% were represented by Enterobacterales, where Escherichia coli stood out with 87.54%, followed by Pseudomonasaeruginosa (2.67%) and Enterococcus faecalis (1.48%). Of the E. coli strains, 87.12% presented resis-tance to at least one antibiotic, with 46.78% MDR and 5.42% XDR. In general, more than half of the uropathogens identified were distributed either as MDR or XDR phenotypes. The results show the need to develop local research to im-prove empirical and targeted therapies in urinary tract infections, in addition to awareness actions for the rational use of antibiotics and epidemiological surveillance of multiresistant strains circulating in the region.

Nitrofurantoin resistance as an indicator for multidrug resistance: an assessment of Escherichia coli urinary tract specimens in England, 2015-19.

To determine whether MDR occurs more frequently in nitrofurantoin-resistant Escherichia coli urinary isolates in England, compared with nitrofurantoin-susceptible isolates. Using routine E. coli urine isolate antibiotic susceptibility laboratory surveillance data for England, 2015-19 inclusive, the percentage of MDR or XDR phenotype was estimated for nitrofurantoin-susceptible and nitrofurantoin-resistant laboratory-reported urinary tract samples by region, patient sex and age group. Resistance to nitrofurantoin among E. coli urinary samples decreased slightly year on year from 2.9% in 2015 to 2.3% in 2019. Among E. coli UTIs tested for nitrofurantoin susceptibility and ≥3 additional antibiotics, the percentage that were MDR was consistently 15%-20% percentage points higher for nitrofurantoin-resistant isolates compared with nitrofurantoin-susceptible isolates. Similarly, the percentage of isolates with an XDR phenotype was higher among nitrofurantoin-resistant versus -susceptible isolates (8.7% versus 1.4%, respectively, in 2019); this disparity was greater in male patients, although variation was seen by age group in both sexes. Regional variation was also noted, with the highest MDR percentage amongst nitrofurantoin-resistant E. coli urinary samples in the London region (36.7% in 2019); the lowest was in the North East (2019: 16.9%). MDR and XDR phenotypes occur more frequently in nitrofurantoin-resistant E. coli urinary isolates in England, compared with nitrofurantoin-susceptible isolates. However, nitrofurantoin resistance is low (<3%) overall. This latest study provides important insights into trends in nitrofurantoin resistance and MDR, which is of particular concern for patients ≥75 years old and those who are male. It also emphasises geographical heterogeneities within England in nitrofurantoin resistance and MDR.

Susceptibility to antimicrobial preparations of Klebsiella pneumoniae strains isolated from patients in a multidisciplinary hospital

Introduction. The extraordinary genetic potential of microorganisms has benefited from human overuse antibiotics to develop multiple resistance mechanisms. The large size and heterogeneity of the Russian population, the presence of territories with significant differences in demographic, cultural, and socio-economic indicators, the features of the management and availability of medical care are significant factors influencing the spread of resistance genes to antibacterial therapy of some strains of microorganisms.&#x0D; Materials and methods. Susceptibility to twenty one antimicrobial agents of one hundred twenty eight Klebsiella pneumoniae isolates, isolated from various loci of patients in a multidisciplinary hospital, including 16% of strains from the lower respiratory tract, 44% from wounds and wound discharge, and 40% from urine, was assessed.&#x0D; Results. Among isolates from urine, 20% of isolates were found to have the multidrug resistance (MDR) phenotype, 42% had the extreme resistance phenotype (XDR). Among the isolates of Kl. pneumoniae from purulent wounds, 18% had the MDR phenotype, and 43% had the XDR phenotype. Among the isolates of Kl. Рneumoniae from the lower respiratory tract, 37% had the MDR phenotype, 40% had the XDR phenotype. There are no pan-resistant strains in all groups. &#x0D; The presence of genes for metallo-beta-lactamase (VIM, IMP, NDM groups) and serine carbapenemase (bovine and OXA-48) in molecular genetic study by real-time PCR of isolated Kl. pneumoniae was found in 73.4% of cases. &#x0D; The results of determining the sensitivity of the isolates revealed a low activity of amoxicillin / clavulanic acid, III and IV generation cephalosporins (ceftazidime, cefotaxime, cefepime). 86.7% of isolates are resistant to drugs of the aminoglycoside group (amikacin), and 100% to gentamicin. Of the group of carbapenems, meropenem showed the highest activity – 26.6%, about 7% were sensitive to ertapenem. From the group of fluoroquinolones, sensitivity ranged from 20 to 30%. The highest activity of all drugs was shown by ticarcillin/clavulanate – 33.3%.&#x0D; Limitations. The criteria for inclusion in the group of examination and selection of biomaterial were the presence of previous massive antibacterial therapy in the anamnesis, the presence of catheters, drains, etc.&#x0D; Conclusions. There was established a high proportion of strains Kl. pneumoniae with the phenotype of multiple antibiotic resistance.

Mortality and Outcomes of Patients Infected with Extensively Drug-Resistant Bacteria Admitted to Intensive Care Units

Background: The emergence of antimicrobial-resistant pathogens in intensive care units (ICU) makes treatment of these infections very difficult. Objectives: This study aimed to survey the resistance phenotype, risk factors, and possible treatment options for hospital-acquired infections (HAI) at ICUs in a referral university hospital. Methods: Samples were prepared from ICU patients with HAIs. Pathogens were isolated, and the resistance phenotype, prescribed antibiotics, mortality rate, associated risk factors, and clonal relationship of the isolates were assessed. Results: From 100 patients admitted to ICUs, 76 (76%) showed clinical symptoms of HAIs. The most common sources of infection were lung secretions (51.8%). The isolated bacteria were Gram-negative (77, 90.6%) and Gram-positive (9.4%). The most common isolated microorganism was the Acinetobacter baumannii complex (63.5%). The most effective antimicrobials were colistin (96.1%) and linezolid (100%) for Gram-negative and Gram-positive isolates, respectively. An extensively drug-resistant (XDR) phenotype was documented in all isolates of A. baumannii, Pseudomonas aeruginosa, and Serratia marcescens. The XDR phenotype was a significant risk factor only for mortality. A. baumannii had the highest mortality rate (66.6%) among all the isolates. While A. baumannii strains had limited diversity, the other species were highly divergent. Conclusions: The results revealed a high mortality rate for Gram-negative isolates, especially in adenosine triphosphate-binding cassette (ABC). The high genetic similarities of ABC strains might be an indication of neglecting infection control prevention. The use of cotrimoxazole and colistin instead of carbapenems can be promising for mortality reduction in the studied ICUs.

Persistence of a carbapenem-resistant Acinetobacter baumannii (CRAB) International Clone II (ST2/IC2) sub-lineage involved with outbreaks in two Brazilian clinical settings

BackgroundAcinetobacter baumannii international clone II (IC2) is a widespread pandemic clone, however, it is rarely described in South America. The present study reported an outbreak caused by XDR IC2 strains in a clinical setting in Rio de Janeiro in 2022. MethodsMolecular epidemiology analysis was conducted with MLST to determine the clonal relationship and to assign a sequence type. The antimicrobial resistance profile of A. baumannii strains was assessed by the disk-diffusion method and MIC determination, and the presence of antibiotic resistance genes was determined by PCR and Sanger sequencing. The whole genome of one representative strain (AB91) was sequenced to prospect its resistome and virulome. ResultsThe MLST revealed that all strains belonged to the ST2 (Pasteur scheme) that corresponded to the pandemic IC2 lineage. They presented the XDR phenotype, which was compatible with their resistome composed of several acquired resistance genes and altered housekeeping genes. Additionally, an expressive virulome was revealed in AB91 genome. Genomic comparison with the unique other available IC2 genome from Brazil revealed that outbreaks occurring during (São Paulo - 2020/2021) and after (Rio de Janeiro - 2022) COVID-19 pandemics were caused by the same IC2 lineage. ConclusionsThis study suggests that the presence of a huge arsenal of resistance and virulence genes may have contributed to the persistence and the successful establishment of IC2 in Brazilian clinical settings during and after the COVID-19 pandemics in response to a series of events, such as the antibiotic overused during that period.

Compassionate use of a novel β-lactam enhancer-based investigational antibiotic cefepime/zidebactam (WCK 5222) for the treatment of extensively-drug-resistant NDM-expressing Pseudomonas aeruginosa infection in an intra-abdominal infection-induced sepsis patient: a case report

Infections in critically-ill patients caused by extensively-drug-resistant (XDR)-Pseudomonas aeruginosa are challenging to manage due to paucity of effective treatment options. Cefepime/zidebactam, which is currently in global Phase 3 clinical development (Clinical Trials Identifier: NCT04979806, registered on July 28, 2021) is a novel mechanism of action based β-lactam/ β-lactam-enhancer combination with a promising activity against a broad-range of Gram-negative pathogens including XDR P. aeruginosa. We present a case report of an intra-abdominal infection-induced sepsis patient infected with XDR P. aeruginosa and successfully treated with cefepime/zidebactam under compassionate use. The 50 year old female patient with past-history of bariatric surgery and recent elective abdominoplasty and liposuction developed secondary pneumonia and failed a prolonged course of polymyxins. The organism repeatedly isolated from the patient was a New-Delhi metallo β-lactamase-producing XDR P. aeruginosa resistant to ceftazidime/avibactam, imipenem/relebactam and ceftolozane/tazobactam, susceptible only to cefepime/zidebactam. As polymyxins failed to rescue the patient, cefepime/zidebactam was administered under compassionate grounds leading to discharge of patient in stable condition. The present case highlights the prevailing precarious scenario of antimicrobial resistance and the need for novel antibiotics to tackle infections caused by XDR phenotype pathogens.

Genome-Based Retrospective Analysis of a Providencia stuartii Outbreak in Rome, Italy: Broad Spectrum IncC Plasmids Spread the NDM Carbapenemase within the Hospital.

Providencia stuartii is a member of the Morganellaceae family, notorious for its intrinsic resistance to several antibiotics, including last-resort drugs such as colistin and tigecycline. Between February and March 2022, a four-patient outbreak sustained by P. stuartii occurred in a hospital in Rome. Phenotypic analyses defined these strains as eXtensively Drug-Resistant (XDR). Whole-genome sequencing was performed on the representative P. stuartii strains and resulted in fully closed genomes and plasmids. The genomes were highly related phylogenetically and encoded various virulence factors, including fimbrial clusters. The XDR phenotype was primarily driven by the presence of the blaNDM-1 metallo-β-lactamase alongside the rmtC 16S rRNA methyltransferase, conferring resistance to most β-lactams and every aminoglycoside, respectively. These genes were found on an IncC plasmid that was highly related to an NDM-IncC plasmid retrieved from a ST15 Klebsiella pneumoniae strain circulating in the same hospital two years earlier. Given its ability to acquire resistance plasmids and its intrinsic resistance mechanisms, P. stuartii is a formidable pathogen. The emergence of XDR P. stuartii strains poses a significant public health threat. It is essential to monitor the spread of these strains and develop new strategies for their control and treatment.

Complete genome sequence of Pseudomonas aeruginosa PA99 clinical isolate from Thailand carrying two novel class 1 integrons, In2083 and In2084

The aim of this study was to identify and characterize multidrug resistance genes and the genetic contexts of integrons found in extensively drug resistant (XDR) Pseudomonas aeruginosa PA99 clinical isolate from Thailand. The sequencing of P. aeruginosa PA99 genomic DNA was done by using Pacific Biosciences RS II sequencing platform. The generated reads were de novo assembled by Canu version 1.4 and the annotation was performed using Prokka v1.12b. The complete genome sequence was subjected for identification of sequence type, serotype, integrons, and antimicrobial resistance genes by MLST 2.0, PAst 1.0, INTEGRALL, Resfinder 4.1, and CARD 3.2.5, respectively. Pseudomonas aeruginosa PA99 genome consisted of a 6,946,480-bp chromosomal DNA with 65.9% GC and belonged to ST964 and serotype O4. Twenty-one antimicrobial resistance genes conferring XDR phenotype were identified. Of special note were carbapenem resistance genes (blaIMP-1, blaPAO, blaOXA-21, and blaOXA-396) and colistin resistance gene basR with L71R mutation. Integron analysis revealed that P. aeruginosa PA99 harbored five class 1 integrons: two copies of In994 (blaIMP-1), an In1575 (aadB), and two novel integrons, In2083 (blaOXA-21 - aac(6')-Ib3 - aac(6')-Ib-cr - ere(A)1∆2 - dfrA1r) and In2084 (blaIMP-1 - aac(6')-Ib3 - aac(6')-Ib-cr). To the best of our knowledge, this is the first report of two novel class I integrons designated by INTEGRALL as In2083 and In2084 found in XDR-P. aeruginosa PA99 clinical isolate from Thailand. The characterization of genetic contexts of In2083 and In2084 provide the evidence of the assorting of resistance genes to evolve as novel integrons.

Rapid emergence of extensively drug-resistant Shigella sonnei in France

Shigella sonnei, the main cause of bacillary dysentery in high-income countries, has become increasingly resistant to antibiotics. We monitored the antimicrobial susceptibility of 7121 S. sonnei isolates collected in France between 2005 and 2021. We detected a dramatic increase in the proportion of isolates simultaneously resistant to ciprofloxacin (CIP), third-generation cephalosporins (3GCs) and azithromycin (AZM) from 2015. Our genomic analysis of 164 such extensively drug-resistant (XDR) isolates identified 13 different clusters within CIP-resistant sublineage 3.6.1, which was selected in South Asia ∼15 years ago. AZM resistance was subsequently acquired, principally through IncFII (pKSR100-like) plasmids. The last step in the development of the XDR phenotype involved various extended-spectrum beta-lactamase genes (blaCTX-M-3, blaCTX-M-15, blaCTX-M-27, blaCTX-M-55, and blaCTX-M-134) carried by different plasmids (IncFII, IncI1, IncB/O/K/Z) or even integrated into the chromosome, and encoding resistance to 3GCs. This rapid emergence of XDR S. sonnei, including an international epidemic strain, is alarming, and good laboratory-based surveillance of shigellosis will be crucial for informed decision-making and appropriate public health action.

Antimicrobial resistance and biofilm formation capacity among Acinetobacter baumannii strains isolated from patients with burns and ventilator-associated pneumonia.

Acinetobacter baumannii is a pathogen responsible for nosocomial infections, especially in patients with burns and ventilator-associated pneumonia (VAP). The aims of this study was to compare the biofilm formation capacity, antimicrobial resistance patterns and molecular typing based on PFGE (Pulsed-Field Gel Electrophoresis) in A.baumannii isolated from burn and VAP patients. A total of 50 A.baumannii isolates were obtained from burn and VAP patients. In this study, we assessed antimicrobial susceptibility, biofilm formation capacity, PFGE fingerprinting, and the distribution of biofilm-related genes (csuD, csuE, ptk, ataA, and ompA). Overall, 74% of the strains were multidrug resistant (MDR), and 26% were extensively drug-resistant (XDR). Regarding biofilm formation capacity, 52%, 36%, and 12% of the isolates were strong, moderate, and weak biofilm producers. Strong biofilm formation capacity significantly correlated with XDR phenotype (12/13, 92.3%). All the isolates harbored at least one biofilm-related gene. The most prevalent gene was csuD (98%), followed by ptk (90%), ataA (88%), ompA (86%), and csuE (86%). Harboring all the biofilm-related genes was significantly associated with XDR phenotype. Finally, PFGE clustering revealed 6 clusters, among which cluster No. 2 showed a significant correlation with strong biofilm formation and XDR phenotype. Our findings revealed the variable distribution of biofilm-related genes among MDR and XDR A.baumannii isolates from burn and VAP patients. A significant correlation was found between strong biofilm formation capacity and XDR phenotype. Finally, our results suggested that XDR phenotype was predominant among strong-biofilm producer A.baumannii in our region.

1676. Activity of SPR206 and Comparator Agents Against Pseudomonas aeruginosa and Acinetobacter baumannii Causing Infections in United States Hospitals

Abstract Background SPR206 is a next generation polymyxin being developed to treat serious infections caused by Gram-negative (GN) multidrug-resistant (MDR) pathogens. The in vitro activity of SPR206 and comparators were monitored against GN pathogens causing infection in US and European hospitals during 2021 as part of the SENTRY Antimicrobial Surveillance Program. This study reports the activity of SPR206 against A. baumannii-calcoaceticus species complex (ACB) and P. aeruginosa (PSA) recovered from patients hospitalized in the USA. Methods A total of 238 ACB and 450 PSA recovered from clinical samples during the SENTRY Program for 2021 were included in the study. Isolates were collected from sites in all 9 US Census Divisions and centrally tested for susceptibility by CLSI broth microdilution method and interpretations. Results A total of 34.9% (83/238) and 14.7% (35/238) ACB displayed an MDR or XDR phenotype, whereas 17.8% (80/450) and 8.0% (36/450) PSA had these phenotypes, respectively. Overall, SPR206 had MIC50/90 of 0.12/0.5 mg/L against all ACB, whereas colistin (COL) had MIC50/90 results of 0.5/1 mg/L. SPR206 and COL inhibited, respectively, 98.0% and 97.0% of ACB at MIC of ≤2 mg/L. Other agents tested against ACB showed MIC90 of &amp;gt;16 mg/L. SPR206 remained active against the MDR (MIC50/90, 0.12/1 mg/L) and XDR (MIC50/90, 0.12/0.25 mg/L) subsets of ACB, as did COL (MIC50/90, 0.5/1 mg/L). MIC50, MIC90, and MIC100 of 0.25 mg/L, 0.25 mg/L, and 2 mg/L were obtained for SPR206 against all PSA, respectively. COL (MIC50/90, 1/1 mg/L), ceftazidime-avibactam (MIC50/90, 2/8 mg/L; 94.9% susceptible), and ceftolozane-tazobactam (MIC50/90, 0.5/2 mg/L; 96.9% susceptible) were active against PSA. SPR206 (MIC50/90, 0.25/0.5 mg/L) and COL (MIC50/90, 1/1 mg/L) remained active against the MDR and XDR PSA subsets. Conclusion SPR206 showed potent in vitro activity against these recent collections of ACB and PSA from the USA. SPR206 potency was consistently greater than clinically available in-class and other comparator agents. These results, and favorable safety and tolerability profiles of SPR206 in Phase 1 studies, support the clinical development of SPR206 for the usually difficult-to-treat infections caused by these pathogens and their resistant subsets. Disclosures Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support SJ Ryan Arends, PhD, AbbVie: Grant/Research Support|GSK: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Shionogi: Grant/Research Support Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.

Multidrug-Resistant and Extremely Drug-Resistant Pseudomonas aeruginosa in Clinical Samples From a Tertiary Healthcare Facility in Nigeria.

Pseudomonas aeruginosa has been globally implicated in healthcare-associated infection. The susceptibility pattern of clinical isolates of P. aeruginosa to anti-pseudomonal antibiotics is reported. Clinical samples, namely blood, urine, tracheal aspirate, cerebrospinal fluid (CSF), wound swabs, high vaginal swabs, eye, and ear exudates were obtained from patients, processed and identified using standard microbiological protocols. Antibiotic susceptibility testing was undertaken using the Kirby Bauer Disc diffusion method. Results were reported following the Clinical and Laboratory Standards Institute guidelines. Of 104 P. aeruginosa isolates identified, males (52.88%) had a higher incidence of infection than female (47.11%) patients. The highest prevalence was recorded from wound swabs [46 (44.23%)] followed by ear exudates [23 (22.12%)], urine [22 (21.15%)], while eye exudates and samples from the CSF yielded the least [1 (0.96% each)]. From the antibiogram, imipenem had the highest antibiotic activity (91.3%) followed by polymyxin B (84.6%). The isolates exhibited the highest resistance to ceftazidime (73.1%) and piperacillin-tazobactam (61.5%). The antibiotic susceptibility pattern of P. aeruginosa isolates revealed 7.69% susceptible, 26% resistant, 61% multidrug resistance (MDR), 5% extremely drug resistance (XDR), and an absence (0%) of pandrug-resistant phenotypes. The study recorded alarmingly high cases of MDR and some XDR phenotypes of P. aeruginosa in University of Port Harcourt Teaching Hospital. It will help identify existing gaps in antimicrobial resistance surveillance and assist in improving public health policies regarding antibiotic stewardship, initiatives, and interventions.

Genomic insights into the emergence and spread of NDM-1-producing Vibrio spp. isolates in China.

Carbapenemase-producing Vibrio spp., which exhibit an XDR phenotype, have become increasingly prevalent and pose a severe threat to public health. To investigate the genetic characteristics of NDM-1-producing Vibrio spp. isolates and the dissemination mechanisms of blaNDM-1 in Vibrio. A total of 1363 non-duplicate Vibrio spp. isolates collected from shrimp samples in China were subjected to antimicrobial susceptibility tests and screened for blaNDM-1. The blaNDM-1-positive isolates were further characterized by PFGE, MLST, conjugation and WGS using Illumina and Nanopore platforms. Plasmid stability and fitness cost were assessed using Escherichia coli J53, Klebsiella pneumoniae Kpt80 and Salmonella spp. SA2051 as recipient strains. In total, 13 blaNDM-1-positive isolates were identified, all exhibiting MDR. WGS analysis revealed that the 13 blaNDM-1 genes were all associated with a derivative of Tn125. Plasmid analysis revealed that six blaNDM-1 genes were located in IncC plasmids and the other seven were carried by plasmids of two different novel types. Conjugation and plasmid stability assays showed that only the IncC plasmids could be transferred to all the recipient strains and could be stably maintained in the hosts. The emergence of the novel plasmids has contributed to the variable genetic contexts of blaNDM-1 in Vibrio spp. and IncC plasmids harbouring the blaNDM-1 gene could facilitate the spread of such genes between Vibrio spp. and other zoonotic pathogens, leading to a rapid dissemination of blaNDM-1 in bacterial pathogens worldwide.

Surgical Site Infections in Post-Living Donor Liver Transplantation: Surveillance and Evaluation of Care Bundle Approach

Background and Aim: Although implantation of a care bundle approach is well established in intensive care units (ICUs), yet its impact on reducing surgical site infections (SSI) among post living-donor-liver transplantation (LDLT) patients has not been established. Our aim is to evaluate the impact of a care bundle in reducing SSI and to detect the pattern of antibiotic resistance in LDLT. Materials and Methods: This before and after comparative study was conducted at Elmanial specialized tertiary hospital, Cairo University over a period of 3 years (January 2016 - December 2018) including 57 LDLT patients. We introduced a care bundle comprised of a group of evidence-based practices implemented together. The study was divided into three phases. All bacterial identification and antibiotic sensitivity testing were done by a Vitek 2 compact system. Results: SSIs rates were reduced significantly by 30.4% from the pre-implementation to the post implementation phase (from 13/24, 54.2% to 5/21, 23.8%, OR 0.21, CI 95%: 1.137- 0.039). This reduction went hand in hand with increase in the hand hygiene compliance from 57.3 % to 78 %, then remained sustained with a median rate of 78% in the last 6 months. Klebsiella pneumoniae 11\25 (44% of SSIs), Acinetobacter baumannii 8\25 (32% of SSIs), Escherichia coli 5\25 (20%), Pseudomonas aeruginosa 5\25 (20%) and MRSA 4\25 (16%). With predominance of XDR phenotype 14/25 (56%), followed by ESBL of gram-negative bacteria 6/25 (24%), then MRSA 4/25 (16%). Conclusion: SSIs in LDLT mandates strict implementation of comprehensive evidence-based care bundles for better patent outcome.

Molecular characterisation of Acinetobacter baumannii isolates from bloodstream infections in a tertiary-level hospital in South Africa.

Acinetobacter baumannii is an opportunistic pathogen and causes various infections in patients. This study aimed to describe the clinical, epidemiological and molecular characteristics of A. baumannii isolated from BCs in patients at a tertiary-level hospital in South Africa. Ninety-six isolates from bloodstream infections were collected. Clinical characteristics of patients were recorded from patient files. Organism identification and AST was performed using automated systems. PCR screening for the mcr-1 to mcr-5 genes was done. To infer genetic relatedness, a dendrogram was constructed using MALDI-TOF MS. All colistin-resistant isolates (n = 9) were selected for WGS. The patients were divided into three groups, infants (<1 year; n = 54), paediatrics (1–18 years; n = 6) and adults (≥19 years; n = 36) with a median age of 13 days, 1 and 41 years respectively. Of the 96 A. baumannii bacteraemia cases, 96.9% (93/96) were healthcare-associated. The crude mortality rate at 30 days was 52.2% (48/92). The majority of the isolates were multidrug-resistant (MDR). All isolates were PCR-negative for the mcr-1 to mcr-5 genes. The majority of the isolates belonged to cluster 1 (62/96) according to the MALDI-TOF MS dendrogram. Colistin resistance was confirmed in nine A. baumannii isolates (9.4%). The colistin-resistant isolates belonged to sequence type (ST) 1 (5/6) and ST2 (1/6). The majority of ST1 isolates showed low SNP diversity (≤4 SNPs). All the colistin-resistant isolates were resistant to carbapenems, exhibited an XDR phenotype and harboured the blaOXA–23 gene. The blaNDM gene was only detected in ST1 colistin-resistant isolates (n = 5). The lpsB gene was detected in all colistin-resistant isolates as well as various efflux pump genes belonging to the RND, the MFS and the SMR families. The lipooligosaccharide OCL1 was detected in all colistin-resistant ST1 and ST2 isolates and the capsular polysaccharide KL3 and KL17 were detected in ST2 and ST1 respectively. This study demonstrated a 9.4% prevalence of colistin-resistant ST1 and ST2 A. baumannii in BC isolates. The detection of the lpsB gene indicates a potential threat and requires close prospective monitoring.