When More is Still Not Enough: A Case of Ceftazidime-Avibactam Resistance in a Burn Patient

2021 ◽  
Author(s):  
Shelbye R Herbin ◽  
Katie E Barber ◽  
Andrew R Isaacson ◽  
Heather S Dolman ◽  
Jessica D McGee ◽  
...  
Keyword(s):  
Genetic Markers ◽  
Total Body Surface Area ◽  
Multidrug Resistant ◽  
Therapeutic Drug ◽  
Thermal Burn ◽  
Failure Data ◽  
Development Of Resistance ◽  
Genes Encoding ◽  
Resistance Patterns ◽  
Burn Patient

Abstract Burn patients have numerous risk factors for multidrug resistant organisms (MDROs) and altered pharmacokinetics, which both independently increase the risk of treatment failure. Data on appropriate antimicrobial dosing are limited in this population and therapeutic drug monitoring (TDM) for beta-lactams is impractical at most facilities. 1-3 Technology is available that can detect genetic markers of resistance, but they are not all encompassing, and often require specialized facilities that can detect less common genetic markers. 4-5 Newer antimicrobials can help combat MDROs, but additional resistance patterns may evolve during treatment. Considering drug shortages and antimicrobial formularies, clinicians must remain vigilant when treating infections. This case report describes the development of resistance to ceftazidime-avibactam in a burn patient. The patient was a 54- year-old burn victim with a 58% total body surface area (TBSA) thermal burn who underwent multiple courses of antibiotics for various Pseudomonal infections. The initial Pseudomonal wound infection was sensitive to cefepime, aminoglycosides, and meropenem. A subsequent resistant pseudomonal pneumonia was treated with ceftazidime-avibactam 2.5 grams every 6 hours due to the elevated MIC to cefepime (16mcg/mL) and meropenem (>8mcg/mL). Although, the patient improved over 7 days, the patient again spiked fevers and had increased white blood counts (WBC). Repeat blood cultures demonstrated a multidrug resistant (MDR) Pseudomonas with a minimum inhibitory concentration (MIC) to ceftazidime-avibactam of 16mcg/mL, which is above the Clinical and Laboratory Standards Institute (CLSI) breakpoint of 8mcg/mL. At first, resistance was thought to have occurred due to inadequate dosing, but genetic work demonstrated multiple genes encoding beta-lactamases.

scholarly journals Cumulative antibiogram and multidrug-resistant organisms in a regional equine referral hospital

2020 ◽  
Vol 33 (1) ◽  
pp. 149-155
Author(s):  
Ka Y. Yuen ◽  
Justine S. Gibson ◽  
Sophia Hinrichsen ◽  
Carlos E. Medina-Torres ◽  
Francois-Rene Bertin ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Multidrug Resistant ◽  
Referral Hospital ◽  
Advisory Group ◽  
Evidence Based ◽  
Local Resistance ◽  
Development Of Resistance ◽  
Technical Advisory Group ◽  
Resistance Patterns ◽  
Culture Positive

Prudent use of antimicrobials is paramount to slow the development of resistance and for successful treatment. The use of cumulative antibiograms will allow evidence-based antimicrobial selection with consideration of local resistance patterns. We generated a “first-isolate-per-patient” cumulative antibiogram for a regional equine referral hospital. Bacterial organisms cultured from horses between 2011 and 2018, sample origin, antimicrobial susceptibilities, and multidrug-resistant (MDR) status were tabulated. Of 1,176 samples, 50% were culture positive. Overall, 93 of 374 (25%) were MDR. Of the MDR isolates, 11 (12%) were susceptible to high-importance antimicrobials only (as defined by the Australian Strategic and Technical Advisory Group on antimicrobial resistance). β-hemolytic streptococci were uniformly susceptible to penicillin (76 of 76); 17 of 20 (85%) non–β-hemolytic Streptococcus spp. were susceptible to penicillin. Despite veterinary-specific challenges in constructing an antibiogram, our study provides an exemplar of the clinical utility of regional-, farm-, or hospital-specific cumulative antibiograms for evidence-based empirical antimicrobial selection by veterinarians prior to susceptibility result availability.

scholarly journals Complement Susceptibility in Relation to Genome Sequence of RecentKlebsiella pneumoniaeIsolates from Thai Hospitals

mSphere ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Jessica Loraine ◽  
Eva Heinz ◽  
Jessica De Sousa Almeida ◽  
Oleksandr Milevskyy ◽  
Supayang P. Voravuthikunchai ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Single Gene ◽  
Multidrug Resistant ◽  
Side Chains ◽  
Content Type ◽  
Genes Encoding ◽  
Resistance Patterns ◽  
Tertiary Hospitals ◽  
Population Structures ◽  
Antibiotic Resistance Patterns

ABSTRACTThe capacity to resist the bactericidal action of complement (C′) is a strong but poorly understood virulence trait inKlebsiellaspp. Killing requires activation of one or more C′ pathways, assembly of C5b-9 membrane attack complexes (MACs) on the surface of the outer membrane (OM), and penetration of MACs into the target bilayer. We interrogated whole-genome sequences of 164Klebsiellaisolates from three tertiary hospitals in Thailand for genes encoding surface-located macromolecules considered to play a role in determination of C′ resistance. Most isolates (154/164) were identified asKlebsiella pneumoniae, and the collection conformed to previously established population structures and antibiotic resistance patterns. The distribution of sequence types (STs) and capsular (K) types were also typical of global populations. The majority (64%) of isolates were resistant to C′, and the remainder were either rapidly or slowly killed. All isolates carried genes encoding capsular polysaccharides (K antigens), which have been strongly linked to C′ resistance. In contrast to previous reports, there were no differences in the amount of capsule produced by C′-resistant isolates compared to C′-susceptible isolates, nor was there any correlation between serum reactivity and the presence of hypermucoviscous capsules. Similarly, there were no correlations between the presence of genes specifying lipopolysaccharide O-side chains or major OM proteins. Some virulence factors were found more frequently in C′-resistant isolates but were considered to reflect clonal ST expansion. Thus, no single gene accounts for the C′ resistance of the isolates sequenced in this study.IMPORTANCEMultidrug-resistantKlebsiella pneumoniaeis responsible for an increasing proportion of nosocomial infections, and emerging hypervirulentK. pneumoniaeclones now cause severe community-acquired infections in otherwise healthy individuals. These bacteria are adept at circumventing immune defenses, and most survive and grow in serum; their capacity to avoid C′-mediated destruction is correlated with their invasive potential. Killing of Gram-negative bacteria occurs following activation of the C′ cascades and stable deposition of C5b-9 MACs onto the OM. ForKlebsiella, studies with mutants and conjugants have invoked capsules, lipopolysaccharide O-side chains, and OM proteins as determinants of C′ resistance, although the precise roles of the macromolecules are unclear. In this study, we sequenced 164Klebsiellaisolates with different C′ susceptibilities to identify genes involved in resistance. We conclude that no single OM constituent can account for resistance, which is likely to depend on biophysical properties of the target bilayer.

scholarly journals Improving the Inhibitory Effect of Phages against Pseudomonas aeruginosa Isolated from a Burn Patient Using a Combination of Phages and Antibiotics

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 334
Author(s):  
Bahareh Lashtoo Aghaee ◽  
Mohammadali Khan Mirzaei ◽  
Mohammad Yousef Alikhani ◽  
Ali Mojtahedi ◽  
Corinne F. Maurice
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
Ph Values ◽  
Development Of Resistance ◽  
New Antibiotics ◽  
Different Temperatures ◽  
Additional Support ◽  
Burn Patient

Antibiotic resistance causes around 700,000 deaths a year worldwide. Without immediate action, we are fast approaching a post-antibiotic era in which common infections can result in death. Pseudomonas aeruginosa is the leading cause of nosocomial infection and is also one of the three bacterial pathogens in the WHO list of priority bacteria for developing new antibiotics against. A viable alternative to antibiotics is to use phages, which are bacterial viruses. Yet, the isolation of phages that efficiently kill their target bacteria has proven difficult. Using a combination of phages and antibiotics might increase treatment efficacy and prevent the development of resistance against phages and/or antibiotics, as evidenced by previous studies. Here, in vitro populations of a Pseudomonas aeruginosa strain isolated from a burn patient were treated with a single phage, a mixture of two phages (used simultaneously and sequentially), and the combination of phages and antibiotics (at sub-minimum inhibitory concentration (MIC) and MIC levels). In addition, we tested the stability of these phages at different temperatures, pH values, and in two burn ointments. Our results show that the two-phages-one-antibiotic combination had the highest killing efficiency against the P. aeruginosa strain. The phages tested showed low stability at high temperatures, acidic pH values, and in the two ointments. This work provides additional support for the potential of using combinations of phage–antibiotic cocktails at sub-MIC levels for the treatment of multidrug-resistant P. aeruginosa infections.

Antimicrobial Resistance and Presence of Class 1 Integrons Among Different Serotypes of Salmonella spp. Recovered From Children with Diarrhea in Tehran, Iran

2020 ◽  
Vol 20 (2) ◽  
pp. 160-166
Author(s):  
Seyedeh Hanieh Eshaghi Zadeh ◽  
Hossein Fahimi ◽  
Fatemeh Fardsanei ◽  
Mohammad Mehdi Soltan Dallal
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Multidrug Resistant ◽  
Salmonella Spp ◽  
Class 1 Integron ◽  
Class 1 Integrons ◽  
Food Borne ◽  
Class 1 ◽  
Resistance Patterns ◽  
C 30

Background: Salmonellosis is a major food-borne disease worldwide. The increasing prevalence of antimicrobial resistance among food-borne pathogens such as Salmonella spp. is concerning. Objective: The main objective of this study is to identify class 1 integron genes and to determine antibiotic resistance patterns among Salmonella isolates from children with diarrhea. Methods: A total of 30 Salmonella isolates were recovered from children with diarrhea. The isolates were characterized for antimicrobial susceptibility and screened for the presence of class 1 integron genes (i.e. intI1, sulI1, and qacEΔ1). Results: The most prevalent serotype was Enteritidis 36.7%, followed by Paratyphi C (30%), and Typhimurium (16.7%). The highest rates of antibiotic resistance were obtained for nalidixic acid (53.3%), followed by streptomycin (40%), and tetracycline (36.7%). Regarding class 1 integrons, 36.7%, 26.7%, and 33.3% of the isolates carried intI1, SulI, and qacEΔ1, respectively, most of which (81.8%) were multidrug-resistant (MDR). Statistical analysis revealed that the presence of class 1 integron was significantly associated with resistance to streptomycin and tetracycline (p = 0.042). However, there was no association between class 1 integron and other antibiotics used in this study (p > 0.05). Conclusion: The high frequency of integron class 1 gene in MDR Salmonella strains indicates that these mobile genetic elements are versatile among different Salmonella serotypes, and associated with reduced susceptibility to many antimicrobials.

scholarly journals Detection of extended spectrum beta-lactamase genes in Pseudomonas aeruginosa isolated from patients in rural Eastern Cape Province, South Africa

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mojisola C. Hosu ◽  
Sandeep D. Vasaikar ◽  
Grace E. Okuthe ◽  
Teke Apalata
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Multidrug Resistant ◽  
High Rate ◽  
Infection Prevention And Control ◽  
Beta Lactamase ◽  
Eastern Cape ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
Resistance Patterns

AbstractThe proliferation of extended spectrum beta-lactamase (ESBL) producing Pseudomonas aeruginosa represent a major public health threat. In this study, we evaluated the antimicrobial resistance patterns of P. aeruginosa strains and characterized the ESBLs and Metallo- β-lactamases (MBL) produced. Strains of P. aeruginosa cultured from patients who attended Nelson Mandela Academic Hospital and other clinics in the four district municipalities of the Eastern Cape between August 2017 and May 2019 were identified; antimicrobial susceptibility testing was carried out against thirteen clinically relevant antibiotics using the BioMérieux VITEK 2 and confirmed by Beckman autoSCAN-4 System. Real-time PCR was done using Roche Light Cycler 2.0 to detect the presence of ESBLs; blaSHV, blaTEM and blaCTX-M genes; and MBLs; blaIMP, blaVIM. Strains of P. aeruginosa demonstrated resistance to wide-ranging clinically relevant antibiotics including piperacillin (64.2%), followed by aztreonam (57.8%), cefepime (51.5%), ceftazidime (51.0%), piperacillin/tazobactam (50.5%), and imipenem (46.6%). A total of 75 (36.8%) multidrug-resistant (MDR) strains were observed of the total pool of isolates. The blaTEM, blaSHV and blaCTX-M was detected in 79.3%, 69.5% and 31.7% isolates (n = 82), respectively. The blaIMP was detected in 1.25% while no blaVIM was detected in any of the strains tested. The study showed a high rate of MDR P. aeruginosa in our setting. The vast majority of these resistant strains carried blaTEM and blaSHV genes. Continuous monitoring of antimicrobial resistance and strict compliance towards infection prevention and control practices are the best defence against spread of MDR P. aeruginosa.

scholarly journals First Case of Staphylococci Carrying Linezolid Resistance Genes from Laryngological Infections in Poland

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 335
Author(s):  
Michał Michalik ◽  
Maja Kosecka-Strojek ◽  
Mariola Wolska ◽  
Alfred Samet ◽  
Adrianna Podbielska-Kubera ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Resistance Genes ◽  
Ribosomal Proteins ◽  
Multidrug Resistant ◽  
Aureus Strain ◽  
Coagulase Negative Staphylococci ◽  
Spa Typing ◽  
Linezolid Resistance ◽  
First Case ◽  
Resistance Patterns

Linezolid is currently used to treat infections caused by multidrug-resistant Gram-positive cocci. Both linezolid-resistant S. aureus (LRSA) and coagulase-negative staphylococci (CoNS) strains have been collected worldwide. Two isolates carrying linezolid resistance genes were recovered from laryngological patients and characterized by determining their antimicrobial resistance patterns and using molecular methods such as spa typing, MLST, SCCmec typing, detection of virulence genes and ica operon expression, and analysis of antimicrobial resistance determinants. Both isolates were multidrug resistant, including resistance to methicillin. The S. aureus strain was identified as ST-398/t4474/SCCmec IVe, harboring adhesin, hemolysin genes, and the ica operon. The S. haemolyticus strain was identified as ST-42/mecA-positive and harbored hemolysin genes. Linezolid resistance in S. aureus strain was associated with the mutations in the ribosomal proteins L3 and L4, and in S. haemolyticus, resistance was associated with the presence of cfr gene. Moreover, S. aureus strain harbored optrA and poxtA genes. We identified the first case of staphylococci carrying linezolid resistance genes from patients with chronic sinusitis in Poland. Since both S. aureus and CoNS are the most common etiological factors in laryngological infections, monitoring of such infections combined with surveillance and infection prevention programs is important to decrease the number of linezolid-resistant staphylococcal strains.

scholarly journals Antibiotic Resistance of Uropathogens Isolated from Patients Hospitalized in District Hospital in Central Poland in 2020

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 447
Author(s):  
Barbara Kot ◽  
Agata Grużewska ◽  
Piotr Szweda ◽  
Jolanta Wicha ◽  
Urszula Parulska
Keyword(s):  
Antibiotic Resistance ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Disk Diffusion Method ◽  
Beta Lactamases ◽  
E Coli ◽  
Central Poland ◽  
Resistance Patterns ◽  
Extended Spectrum Beta Lactamases ◽  
Tract Infections

The aim of this study was to determine antibiotic resistance patterns and the prevalence of uropathogenes causing urinary tract infections (UTIs) in patients hospitalized in January–June 2020 in central Poland. Antimicrobial susceptibility testing was performed using the disk-diffusion method. Escherichia coli (52.2%), Klebsiella pneumoniae (13.7%), Enterococcus faecalis (9.3%), E. faecium (6.2%), and Proteus mirabilis (4,3%) were most commonly isolated from urine samples. E. coli was significantly more frequent in women (58.6%) (p = 0.0089) and in the age group 0–18, while K. pneumoniae was more frequent in men (24.4%) (p = 0.0119) and in individuals aged 40–60 and >60. Gram-negative species showed resistance to ampicillin. K. pneumoniae were resistant to amoxicillin plus clavulanic acid (75.0%), piperacillin plus tazobactam (76.2%), cefotaxime (76.2%), cefuroxime (81.0%), ciprofloxacin (81.0%), and trimethoprim plus sulphamethoxazole (81.0%). Carbapenems were effective against all E. coli and P. mirabilis. Some K. pneumoniae (13.6%) produced metallo-β-lactamases (MBLs). E. coli (22.6%), K. pneumoniae (81.8%), and all E. faecium were multidrug-resistant (MDR). Some E. coli (26.2%), K. pneumoniae (63.6%), and P. mirabilis (14.3%) isolates produced extended-spectrum beta-lactamases (ESBL). Vancomycin-resistant E. faecium was also found. This study showed that the possibilities of UTIs therapy using available antibiotics become limited due to the increasing number of antibiotic-resistant uropathogens.

scholarly journals Markers of Genetic Variation in Blue Gourami (Trichogaster trichopterus) as a Model for Labyrinth Fish

Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 228
Author(s):  
Gad Degani ◽  
Isana Veksler-Lublinsky ◽  
Ari Meerson
Keyword(s):  
Growth Hormone ◽  
Genetic Variation ◽  
Genetic Markers ◽  
Basic Research ◽  
Coi Gene ◽  
12S Rrna ◽  
Rrna Gene ◽  
Somatotropic Axis ◽  
Genes Encoding ◽  
Growth And Reproduction

Markers of genetic variation between species are important for both applied and basic research. Here, various genes of the blue gourami (Trichogaster trichopterus, suborder Anabantoidei, a model labyrinth fish), many of them involved in growth and reproduction, are reviewed as markers of genetic variation. The genes encoding the following hormones are described: kisspeptins 1 and 2, gonadotropin-releasing hormones 1, 2, and 3, growth hormone, somatolactin, prolactin, follicle- stimulating hormone and luteinizing hormone, as well as mitochondrial genes encoding cytochrome b and 12S rRNA. Genetic markers in blue gourami, representing the suborder Anabantoidei, differ from those in other bony fishes. The sequence of the mitochondrial cytochrome c oxidase subunit 1 (COI) gene of blue gourami is often used to study the Anabantoidei suborder. Among the genes involved in controlling growth and reproduction, the most suitable genetic markers for distinguishing between species of the Anabantoidei have functions in the hypothalamic–pituitary–somatotropic axis: pituitary adenylate cyclase-activating polypeptide and growth hormone, and the 12S rRNA gene.

scholarly journals OMN6 a novel bioengineered peptide for the treatment of multidrug resistant Gram negative bacteria

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shira Mandel ◽  
Janna Michaeli ◽  
Noa Nur ◽  
Isabelle Erbetti ◽  
Jonathan Zazoun ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Antimicrobial Agents ◽  
Cyclic Peptide ◽  
Safety Margin ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Development Of Resistance ◽  
Cecropin A

AbstractNew antimicrobial agents are urgently needed, especially to eliminate multidrug resistant Gram-negative bacteria that stand for most antibiotic-resistant threats. In the following study, we present superior properties of an engineered antimicrobial peptide, OMN6, a 40-amino acid cyclic peptide based on Cecropin A, that presents high efficacy against Gram-negative bacteria with a bactericidal mechanism of action. The target of OMN6 is assumed to be the bacterial membrane in contrast to small molecule-based agents which bind to a specific enzyme or bacterial site. Moreover, OMN6 mechanism of action is effective on Acinetobacter baumannii laboratory strains and clinical isolates, regardless of the bacteria genotype or resistance-phenotype, thus, is by orders-of-magnitude, less likely for mutation-driven development of resistance, recrudescence, or tolerance. OMN6 displays an increase in stability and a significant decrease in proteolytic degradation with full safety margin on erythrocytes and HEK293T cells. Taken together, these results strongly suggest that OMN6 is an efficient, stable, and non-toxic novel antimicrobial agent with the potential to become a therapy for humans.

Comparison of Prevalence, Antimicrobial Resistance, and Occurrence of Multidrug-Resistant Salmonella in Antimicrobial-Free and Conventional Pig Production

2006 ◽  
Vol 69 (4) ◽  
pp. 743-748 ◽  
Author(s):  
WONDWOSSEN A. GEBREYES ◽  
SIDDHARTHA THAKUR ◽  
W. E. MORGAN MORROW
Keyword(s):  
Antimicrobial Resistance ◽  
Production Systems ◽  
Multidrug Resistant ◽  
Resistance Pattern ◽  
Swine Production ◽  
Significant Difference ◽  
Conventional Farms ◽  
Resistance Patterns ◽  
Conventional Systems ◽  
On Farm

Conventional swine production evolved to routinely use antimicrobials, and common occurrence of antimicrobial-resistant Salmonella has been reported. There is a paucity of information on the antimicrobial resistance of Salmonella in swine production in the absence of antimicrobial selective pressure. Therefore, we compared the prevalence and antimicrobial resistance of Salmonella isolated from antimicrobial-free and conventional production systems. A total of 889 pigs and 743 carcasses were sampled in the study. Salmonella prevalence was significantly higher among the antimicrobial-free systems (15.2%) than the conventional systems (4.2%) (odds ratio [OR] = 4.23; P < 0.05). Antimicrobial resistance was detected against 10 of the 12 antimicrobials tested. The highest frequency of resistance was found against tetracycline (80%), followed by streptomycin (43.4%) and sulfamethoxazole (36%). Frequency of resistance to most classes of antimicrobials (except tetracycline) was significantly higher among conventional farms than antimicrobial-free farms, with ORs ranging from 2.84 for chloramphenicol to 23.22 for kanamycin at the on-farm level. A total of 28 antimicrobial resistance patterns were detected. A resistance pattern with streptomycin, sulfamethoxazole, and tetracycline (n = 130) was the most common multidrug resistance pattern. There was no significant difference in the proportion of isolates with this pattern between the conventional (19.5%) and the antimicrobial-free systems (18%) (OR = 1.8; P > 0.05). A pentaresistance pattern with ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline was strongly associated with antimicrobial-free groups (OR = 5.4; P = 0.01). While showing the higher likelihood of finding antimicrobial resistance among conventional herds, this study also implies that specific multidrug-resistant strains may occur on antimicrobial-free farms. A longitudinal study with a representative sample size is needed to reach more conclusive results of the associations detected in this study.

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