Proteeae Isolates Research Articles

Antimicrobial Susceptibility Trends of Proteeae Isolates From a Tertiary-Care Hospital in Western Saudi Arabia.

The tribe Proteeae comprises Proteus, Providencia, and Morganella species. TheseGram-negative rods are of concern in that they are involved in diverse human infections, particularly in hospital settings. In the last two decades, there has been a sharp increase in infections by multidrug-resistant (MDR) Proteeae. Therefore, the objectives of this study were to: (i) assess the prevalence of infections caused by tribe Proteeae, (ii)determine the antimicrobial susceptibility profile of the test isolates, and (iii) identify the underlying risk factors for acquisition of infection by MDR strains. During the period from January 2019 to December 2020, we conducted a retrospective review of the electronic medical and laboratory records of adult patients who received care at our institution. In addition, we analyzed the risk factors associated with acquisition of infections by members of the tribe Proteeae using univariate and multivariate regression models. Overall 403 adult patients (average age 59.69 ± 20.33 years) were enrolled into this study (196 males; 48.6%, and207 females; 51.4%). Proteus mirabilis was the leading pathogen (70.7%; n=285), followed by Morganella morganii (20.1%; n=81), and Providencia species (9.2%; n=37). Most of the isolates were recovered from urine (59.3%; n=239), followed by wound swabs (23.1%; n=93), with the least from blood samples (1.7%; n=7). Out of 403 Proteeae isolates, 27.3% (n=110) were found to be extended-spectrumβ-lactamase (ESBL)-producers, whereas 18.4% (n=74) were MDR. Patient's age, concomitant diabetes mellitus (DM), and long hospital stays were independently associated with infection by MDR strains. Infections by MDR Proteeae are leading causes for morbidity in our tertiary-care facility. Strict adherence to infection control precautions, as well as effective implementation of antimicrobial stewardship programs, are crucial to overcome these superbugs.

1836. Frequency and Antimicrobial Susceptibility of Gram-negative Bacteria Isolated from Patients with Bloodstream Infections in United States (US) Medical Centers (2020-2021)

Abstract Background Antimicrobial resistance among Gram-negative bacteria (GNB) is a major problem in US hospitals. The development of various β-lactamase inhibitor combinations (BLICs) markedly increased the armamentarium to treat infections caused by GNB in recent years. We evaluated the frequency and antimicrobial susceptibility of GNB causing bloodstream infection (BSI). Methods 5,796 organisms were consecutively collected (1/patient) from patients with BSI in 31 US medical centers in 2020-2021. The collection included 2,893 (49.9%) GNB, which were susceptibility tested against ceftazidime-avibactam (CAZ-AVI), ceftolozane-tazobactam (C-T), meropenem-vaborbactam (MEM-VAB), imipenem-relebactam (IMI-REL), and many comparators by CLSI broth microdilution method. Enterobacterales (ENT) isolates with an ESBL phenotype were screened for β-lactamase genes by whole genome sequencing. Results The most common GNBs were E. coli (41.9%), K. pneumoniae (16.1%), P. aeruginosa (10.2%), and E. cloacae (6.8%). Ceftriaxone susceptibility rates were 80.1%, 82.9%, and 74.0% for E. coli, K. pneumoniae, and E. cloacae, respectively. CAZ-AVI and MEM-VAB showed almost complete activity (≥ 99.7%) against ENT, whereas IMI-REL exhibited limited activity against P. mirabilis and indole-positive Proteeae isolates and C-T showed limited activity against E. cloacae, ESBL-phenotype, and multidrug-resistant (MDR) isolates (Table). CAZ-AVI, MEM-VAB, and IMI-REL were active against 84.2%, 57.9%, and 52.6% of carbapenem-resistant ENT (CRE) isolates, respectively. PSA susceptibility to PIP-TAZ, MEM, and CAZ were 86.1%, 88.5%, and 88.5%, respectively. CAZ-AVI (97.6% susceptible [S]), C-T (97.6%S), IMI-REL (99.0%S), and tobramycin (TOB; 98.3%S) were the most active agents against PSA and retained good activity against piperacillin-tazobactam (PIP-TAZ) nonsusceptible (NS), MEM-NS, and multidrug-resistant (MDR) isolates. Conclusion CAZ-AVI and MEM-VAB were the most active agents against ENT and CAZ-AVI; C-T and IMI-REL were the most active BLICs against PSA. The new BLICs represent valuable treatment options for infections caused by MDR GBNs. CAZ-AVI exhibited a more balanced spectrum against ENT and PSA when compared to other BLICs. Disclosures 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 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 Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Michael D. Huband, BS, AbbVie: Grant/Research Support|Melinta: Grant/Research Support Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support 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.

Antimicrobial susceptibility and distribution of extended-spectrum β-lactamases, AmpC β-lactamases and carbapenemases among Proteus, Providencia and Morganella isolated from global hospitalised patients with intra-abdominal and urinary tract infections: Results of the Study for Monitoring Antimicrobial Resistance Trends (SMART), 2008–2011

ObjectivesThe increasing trend of β-lactam resistance among Enterobacteriaceae is a worldwide problem. This study investigated isolates of the tribe Proteeae (Proteus, Providencia and Morganella) causing intra-abdominal and urinary tract infections from the worldwide Study for Monitoring Antimicrobial Resistance Trends (SMART) collected from 2008–2011. MethodsAntimicrobial susceptibility testing was performed on isolates with an ertapenem minimum inhibitory concentration >0.5mg/L or those phenotypically producing extended-spectrum β-lactamases (ESBLs). ESBLs, AmpC β-lactamases and carbapenemases were detected by multiplex PCR. ResultsA total of 142 isolates, including Proteus mirabilis (n=121), Proteus vulgaris (n=3), Providencia stuartii (n=5), Providencia rettgeri (n=6) and Morganella morganii (n=7), were analysed. Proteus mirabilis was generally susceptible to ertapenem (∼90%) compared with imipenem (≤25%). The most common ESBLs were CTX-M types (n=64), followed by TEM (n=27) and SHV (n=7). CTX-M-1, CTX-M-2 and CTX-M-15 were the dominant CTX-M-type ESBLs in P. mirabilis isolates. CMY (n=14), which included CMY-2 (n=6), was the most common AmpC β-lactamase, followed by DHA (n=6) and FOX (n=4). NDM (n=7), which included NDM-1 (n=4), was the most common carbapenemase, followed by KPC (n=2). Isolates from hospital-associated infections had more complicated β-lactamase combinations than isolates from community-acquired infections. ConclusionThe global emergence and spread of β-lactamase-producing Proteeae isolates are major issues in tackling antimicrobial resistance. Continuous monitoring of antimicrobial resistance trends and developing further resistance surveillance are necessary.

Systematic review of antibacterial activity of eravacycline: a novel fluorocycline against clinically obtained Gram-negative bacteria

Eravacycline (TP-434 or 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline) is a novel fluorocycline antibiotic, which was designed to overcome tetracycline-specific resistance mechanisms. This study aimed to analyze the in-vitro activity of eravacycline against Gram-negative bacteria in published literature, to contribute to the international data on the antimicrobial stewardship programs. A systematic literature review was performed through the electronic databases from January of 2000 to December 2017 to cover all published articles relevant to our scope. Finally, nine studies met our inclusion criteria that were subjected to data extraction and review. The highest activity of eravacycline was against Escherichia coli isolates since in all reports eravacycline at a concentration of 0.5 μg/ml or less inhibited 90% of isolates. In contrast, the lowest activity was seen against Proteeae isolates since except for one report eravacycline at a concentration of at least 2 μg/ml inhibited 90% of isolates. The antibacterial activity of eravacycline against 13 collections of carbapenem-resistant bacteria consists of 1057 isolates was showed that eravacycline at a concentration of 2 μg/ml or less inhibited 90% of isolates. The only exception was for carbapenem-resistant Proteeae which 90% of isolates were inhibited at a concentration of at least 4 μg/ml. In summary, eravacycline has a promising in-vitro antibacterial property against several nosocomial pathogens. This was an encouraging result that provides an option for treatment of infections caused by Gram-negative bacteria, regardless of resistance phenotype. However, further clinical studies are necessitate to provide clinical evidence to support these observations.

Characterization of Quinolone-Resistant Determinants in Tribe Proteeae Isolated from Pet Turtles with High Prevalence of qnrD and Novel gyrB Mutations.

Development of antibiotic resistance in bacteria has challenged significantly in both veterinary and human medicine. In this study, we analyzed the potential risk of pet turtles harboring tribe Proteeae as a source of quinolone-resistant determinants, including plasmid-mediated quinolone resistance (PMQR) genes and target gene alterations in the quinolone resistance-determining region (QRDR). Antimicrobial susceptibility of 54 Proteeae isolates against ciprofloxacin, ofloxacin, levofloxacin, and nalidixic acid was examined. The PMQR genes and QRDR alterations were identified using conventional PCR assays and sequencing. Four isolates were resistant to all quinolones tested in this study. Nine isolates showed resistance to nalidixic acid and showed either intermediate resistance or susceptibility to other tested quinolones. All isolates resistant to one or more tested quinolones harbored mutations in gyrB and some also had gyrA and parC mutations. Of 54, 12 Proteeae isolates displayed the novel E466D, N440T, Q411S, and F417L mutations in gyrB. Among the PMQR genes, 41 (76%) isolates harbored the qnrD gene with the highest prevalence, whereas aac(6')Ib-cr, qnrS, qnrA, and qnrB genes were detected in 28 (52%), 9 (17.0%), 7 (13.0%), and 1 (1.9%) study isolates, respectively. The QRDR analysis of selected mutants revealed that increasing quinolone selective pressure led to a predominance of gyrA mutants. All results indicate that a healthy pet turtle can play as a potential reservoir for quinolone-resistant Proteeae, which it might cause public health risk on pet owners.

Incidence of antibiogram, antibiotic resistance genes and class 1 and 2 integrons in tribe Proteeae with IMP27 gene for the first time in Providencia sp. isolated from pet turtles.

Proteeae is a tribe which consists of three genera: Proteus, Providencia and Morganella. The objective of this study was to determine antimicrobial resistance profile, virulence genotype and class 1 and 2 integrons in Proteeae isolated from pet turtles and to determine the impact of antibiotic resistance on virulence and antimicrobial resistance genes. Integron-positive isolates were used to detect their gene cassette array. Sixty four Proteeae were isolated and all were resistant to macrolides (100%). Among 64 isolates 56, 52, 36 and 25 were resistant to nitrofurans, β-lactams, tetracycline and aminoglycoside respectively. Sixteen (25%) isolates were positive for intI1 while 14 (21·87%) were positive for integrase 2 (intI2). Eleven (17·18%) isolates were positive for class 1 variable region while 7 (10·93%) were positive for class 2 variable region. IMP27, a novel metallo β-lactamase gene was found in Providencia isolates. Proteus sp. were positive for every tested virulence genes and UreC gene was detected in 48·44% followed by zapA (17·19%), mrpA (17·19%) and hlyA (14·06%) genes. In this study, integron associated-antibiotic resistance genes have been identified in Proteeae isolates in a considerable range representing clear threats to public health. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, multidrug-resistant Proteeae isolates had several antibiotic resistance genes. Integrons are important contributors to the development and dissemination of antibiotic resistance. We could detect both class 1 and 2 integrons and several gene cassette arrays in class 1 integron. The gene cassette arrays of the Class 2 integrons contained IMP27-dfrA1-aadA1-catB2-ybeA-ybgA in two isolates. To the best of our knowledge this is the first study to report detection of IMP27 in Providencia rettgeri isolates. All results indicate that healthy pet turtles act as potential reservoirs for Proteeae species with zoonotic potential.

Characterization of Integrons and qnr Genes in Proteeae from a Teaching Hospital in China

Background: Proteeae isolates displaying multidrug-resistance (MDR) are the second most common causes of hospital-associated infections. The aim of this study was to screen class 1-3 integrons and plasmid-mediated quinolone resistance (PMQR) genes in Proteeae isolates from the First Affiliated Hospital of the Wenzhou Medical University. Materials and Methods: 176 Proteeae isolates were collected from clinical specimens of inpatients between January 2011 and December 2013. Susceptibility testing was determined by the agar dilution method. Class 1-3 integrons and PMQR genes were amplified by polymerase chain reaction, and the variable regions of integrons were determined by restriction fragment length polymorphisms. Results: 68.2% Proteeae isolates exhibited MDR phenotypes: 46.6 and 10.8% Proteeae isolates were positive for intI1 and intI2, respectively. The resistance rate of integron-positive isolates to aminoglycosides, fluoroquinolones, and trimethoprim/sulfamethoxazole was significantly higher than integron-negative isolates. Sequence analysis revealed that dfrA1-sat2-aadA1, dfrA1-catB2-sat2-aadA1, and sat2-aadA1 were first detected in Morganella morganii strains isolated from China. PMQR was determined by qnrD in 40 strains (22.7%). Conclusion: Our results indicate that class 1 and 2 integrons are common among Proteeae isolates. Meanwhile, qnrD are highly prevalent in Proteeae isolated from our hospital.

Description and plasmid characterization of the qnrD determinant in Proteeae in Wenzhou, Southern China.

Only limited information is available about the detailed characteristics of qnrD, a plasmid-mediated quinolone resistance (PMQR) gene. This study aimed to understand the distribution of qnrD and the characterization of qnrD-carrying plasmids in Proteeae. The distribution of qnrD genes was investigated by polymerase chain reaction (PCR) amplification in 203 consecutive nonduplicate clinical isolates of Proteeae collected from inpatients at the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. The minimum inhibitory concentrations (MICs) of antibiotics were measured by agar dilution method and other PMQR determinants were also determined by PCR. qnrD was positioned via Southern hybridization and the transferability of qnrD-carrying plasmids was achieved by conjugation experiment. The genetic environment of qnrD was investigated by sequencing, and chromosomal polymorphism for qnrD-positive strains was analyzed by pulsed-field gel electrophoresis (PFGE). Forty strains carried qnrD, showing decreased fluoroquinolone susceptibility or low-level fluoroquinolone resistance. qnrD was encoded on the plasmid of about 2.7kb or 5.2kb in length, which cannot be transferred by liquid conjugation or filter mating, but can be successfully transferred by transduction. The transformants showed 62.5-300-fold increases in the MICs of quinolones compared with the recipient. The plasmids carrying qnrD showed a high similarity with that of Providencia spp. and Proteus vulgaris. PFGE analysis demonstrated that these isolates were divergent and not clone related. qnrD could have originated from Proteeae or presented in these bacteria as a reservoir; furthermore, qnrD could be transferred and spread within the same or across different bacterial species if the plasmids acquired mobile elements under antimicrobial selective pressures.

Epidemiological Studies on Proteeae Isolates from Clinical Specimens in the Laquintinie Hospital in Douala, Cameroon

The tribe Proteeae is a group of bacteria within the family Enterobacteriaceae and is responsible for most cases of nosocomial infections in hospital settings. The objective of this study was to determine the prevalence of members of Proteeae from clinical specimens in Laquintinie hospital in Douala. Specimens were collected from patients and screened for Proteeae using standard microbiological and biochemical methods (API 20 Enterobacteriaceae gallery). Of the 3414 clinical specimens made of 2712 urine, 264 blood, 243 CSF and 195 wounds and burns, 1136 (33.3%) yielded a positive bacterial growth, of which 230 (20.2%) were Gram positive and 906 (79.7%) were Gram negative. 164 (14.4%) isolates were identified as members of Proteeae of which 110 (67.1%) were from urine, 37( 22.6%) from wounds and burns, 10(6.1%) from blood and 7( 4.3%) from CSF. Speciation of the Proteeae isolates showed that 111 (67.7%) were Proteus mirabilis , 21(12.8%) Proteus vulgaris , 11 (6.7%) Providencia alcalifaciens , 6 (3.6%) Providencia stuartii , 4 (2.4%) Morganella morganii and 5 (3.0%) Proteus penneri and Providencia rettgeri . There was a significant difference between the type of clinical specimens and the age of patients (X2 = 52.623 p<0.05). Most Proteeae isolates where susceptible to imipemen, ceftazidine, chloramphenicol, gentamicin, nalidixic acid, ofloxacin and amikacin. These findings have significant clinical and epidemiological implications. Keywords: Proteeae isolates, Clinical specimens, Laquintinie Hospital, Cameroon

Population-based laboratory surveillance for tribe Proteeae isolates in a large Canadian health region

The tribe Proteeae comprises the genera Proteus, Morganella and Providencia. Few studies have specifically investigated the epidemiology of infections caused by the Proteeae, and none has been conducted in a large non-selected population. The present study was a population-based laboratory surveillance in the Calgary Health Region (population 1.2 million), Canada during 2000-2005 that aimed to define the incidence, demographical risk-factors for acquisition and antimicrobial susceptibilities of Proteeae isolates. In total, 5047 patients were identified from whom Proteeae isolates were obtained (an annual incidence of 75.9/100 000), with females and the elderly being at highest risk. Incidence rates were 64.8, 7.7 and 3.4/100,000/year for the genera Proteus, Morganella and Providencia, respectively. Overall, 85% of infections were community-onset, and the overall rate of bacteraemic disease was 2.0/100,000. Compared with other species, Proteus mirabilis occurred at a much higher frequency, especially among females, and was less likely to be isolated from hospital-onset infections or to be part of a polymicrobial infection. Among isolates from community-onset infections, Providencia spp. were less likely to be from outpatients and more likely to be from nursing home residents. There were low overall rates of resistance to ciprofloxacin (4%) and gentamicin (5%), with Prot. mirabilis generally being the most susceptible. Members of the Proteeae were isolated frequently in both the community and hospital settings, but were infrequent causes of invasive disease. The occurrence, demographical risk-factors and microbiology of Proteeae isolates varied according to the individual species.

Proteeae species bacteriuria accompanying Proteeae species groin skin carriage in geriatric outpatients.

There have been numerous reports of Proteeae species urinary tract infections among elderly individuals. To explore a possible urinary carrier source of Proteeae species in this population, the frequency of aerobic gram-negative bacillus (AGNB) bacteriuria at the greater than or equal to 10(2)/ml level was determined in 67 ambulatory elderly outpatients classified as to Proteeae group (Morganella, Proteus, Providencia) groin carriage by a set of two skin cultures obtained at least 1 week apart. None had urethral catheters, symptomatic infections, skin ulcers, or recent antibiotic therapy. We found AGNB bacteriuria in 12 of 15 carriers (80%) and in 21 of 52 noncarriers (40%) (P = 0.009). Proteeae species bacteriuria occurred in eight carriers (53.3%) and six noncarriers (11.5%) (P = 0.001). At the 10(2) to 10(4)/ml level, Proteeae species were isolated in urine specimens from seven carriers (46.7%) and four noncarriers (7.7%) (P = 0.001). There was concordance of species of skin and urine Proteeae isolates in six carriers. By contrast, non-Proteeae AGNB bacteriuria at any level was present in four Proteeae species carriers (26%) and 15 noncarriers (28.8%) (P greater than 0.05). There was a 36.7% frequency of Proteeae species bacteriuria in nursing home residents, in contrast to 8.1% among those living in private homes; this parallels the greater frequency of Proteeae species groin carriage among nursing home residents in the study population. Low-level urinary colonization with Proteeae species accompanying Proteeae species groin skin colonization in elderly individuals is a hitherto unrecognized finding. This may account for the greater frequency of Proteeae species urinary infections in this population.

A survey of IgA protease production among clinical isolates of Proteeae.

A collection of 100 strains of Proteeae, in which all species within the tribe were represented, was examined for IgA protease production. The strains were isolated from various clinical specimens from sick and healthy persons in several countries. IgA protease-producing strains were not found amongst species of Providencia and Morganella but were common in Proteus spp. All the strains of P. mirabilis and P. penneri and many of the strains of P. vulgaris examined produced an EDTA-sensitive protease that cleaved the IgA heavy chain outside the hinge region. The proteus enzyme was different in this respect from the EDTA-sensitive, hinge-cutting proteases of other bacteria. The ability to produce IgA protease was unrelated to the O antigenicity, biotype or bacteriocin type of the strain. IgA protease production may be an important virulence mechanism for Proteus strains.

Speciation, serotyping, antimicrobial sensitivity and plasmid content of Proteeae from the environment of calf-rearing units in South West England.

A survey was undertaken of the occurrence, serotype, antimicrobial sensitivity and plasmid content of members of the tribe Proteeae in the environment of two calf-rearing units in the county of Avon in South West England. Examples of the following species were found: Proteus mirabilis, Prot. vulgaris, Prot. vulgaris Biogroup 2, Morganella morganii, Providencia stuartii, Prov. alcalifaciens and Prov. rettgeri. A wide range of serotypes was found, many having been previously reported from nosocomial isolates. A total of 15% of isolates carried plasmids; six pairs of isolates were identified which had identical serotypes but different patterns of plasmid carriage. The antimicrobial sensitivity of the isolates was generally similar to isolates of Proteeae from humans. Although no truly aminoglycoside-resistant isolates were found, some isolates of Prov. stuartii and Prov. rettgeri had MIC's higher than the other isolates to gentamicin and netilmicin, suggesting the presence of low levels of the enzyme AAC 2'. The study demonstrates that there is a considerable diversity of species and types of Proteeae associated with calves and their environment. It seems likely that a potential cause of colonization of the human gut by Proteeae is the consumption of meat.