Clinical and Economic Burden of Bacteraemia Due To Multi-Drug-Resistant Organisms in Korea: A Prospectively Selected Case Control Study

Author(s):  
Kyoung-Ho Song ◽  
Chung-Jong Kim ◽  
Nam-Kyong Choi ◽  
Jeonghoon Ahn ◽  
Pyoeng Gyun Choe ◽  
...  

Abstract BackgroundMultidrug-resistant organisms (MDROs), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug resistant Acinetobacter baumannii (MRAB), multidrug resistant Pseudomonas aeruginosa (MRPA), and carbapenem-resistant Enterobacteriaceae (CRE) are particularly important public health threats, but their detailed clinical outcomes and socioeconomic burden are adequately addressed.MethodsWe prospectively searched for these MDROs bacteraemia cases with matched controls from 10 hospitals across Korea, in a 6-month period, in 2017. Patients were classified into the MDRO, susceptible organism, and no-infection groups. The corresponding susceptible or no-infection controls had similar principal diagnosis at admission time, major surgery or intervention during hospitalization, age (± 10 years), sex, and within ± 60 days of admission date. We collected detailed clinical information and estimated the total additional direct medical cost of each MDRO bacteraemia case using the multistate model. ResultsOf 486 MDRO bacteraemia cases identified for MRSA, MRAB, MRPA, CRE, and VRE, at 260, 87, 18, 20, and 101, respectively, their 90-day mortality rates (overall, 40.3%) were 30.4%, 63.2%, 16.7%, 55.0%, and 47.5%, respectively. Their additional medical costs (overall, $27,700) were $15,768, $35,682, $39,908, $72,051, and $33,662 (compared to the no-infection group), respectively. Overall, these five MDRO bacteraemia cases occurred in 7,979 patients, caused 3,280 deaths, and cost $294,505,002 (range, $170,627,020 to $416,094,679) socioeconomic loss. ConclusionsTremendous clinical and economic burden occurred with MDRO bacteraemia compared with those of antibiotic-susceptible and no-infection groups. Substantial investment and efforts by related government agencies and medical staffs are needed to urgently prevent the increase, spread and expansion of antibiotic-resistant bacteria.

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 495
Author(s):  
Masateru Nishiyama ◽  
Susan Praise ◽  
Keiichi Tsurumaki ◽  
Hiroaki Baba ◽  
Hajime Kanamori ◽  
...  

There is increasing attention toward factors that potentially contribute to antibiotic resistance (AR), as well as an interest in exploring the emergence and occurrence of antibiotic resistance bacteria (ARB). We monitored six ARBs that cause hospital outbreaks in wastewater influent to highlight the presence of these ARBs in the general population. We analyzed wastewater samples from a municipal wastewater treatment plant (MWWTP) and hospital wastewater (HW) for six species of ARB: Carbapenem-resistant Enterobacteria (CARBA), extended-spectrum β-lactamase producing Enterobacteria (ESBL), multidrug-resistant Acinetobacter (MDRA), multidrug-resistant Pseudomonas aeruginosa (MDRP), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE). We registered a high percentage of ARBs in MWWTP samples (>66%) for all ARBs except for MDRP, indicating a high prevalence in the population. Percentages in HW samples were low (<78%), and no VRE was detected throughout the study. CARBA and ESBL were detected in all wastewater samples, whereas MDRA and MRSA had a high abundance. This result demonstrated the functionality of using raw wastewater at MWWTP to monitor the presence and extent of ARB in healthy populations. This kind of surveillance will contribute to strengthening the efforts toward reducing ARBs through the detection of ARBs to which the general population is exposed.


mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Roberto Adamo ◽  
Immaculada Margarit

ABSTRACT Antibiotics and vaccines have greatly impacted human health in the last century by dramatically reducing the morbidity and mortality associated with infectious diseases. The recent challenge posed by the emergence of multidrug-resistant bacteria could possibly be addressed by novel immune prophylactic and therapeutic approaches. Among the newly threatening pathogens, Klebsiella pneumoniae is particularly worrisome in the nosocomial setting, and its surface polysaccharides are regarded as promising antigen candidates. The majority of Klebsiella carbapenem-resistant strains belong to the sequence type 158 (ST258) lineage, with two main clades expressing capsular polysaccharides CPS1 and CPS2. In a recent article, S. D. Kobayashi and colleagues (mBio 9:e00297-18, 2018, https://doi.org/10.1128/mBio.00297-18) show that CPS2-specific IgGs render ST258 clade 2 bacteria more sensitive to human serum and phagocytic killing. E. Diago-Navarro et al. (mBio 9:e00091-18, 2018, https://doi.org/10.1128/mBio.00091-18) generated two murine monoclonal antibodies recognizing distinct glycotopes of CPS2 that presented functional activity against multiple ST258 strains. These complementary studies represent a step toward the control of this dangerous pathogen.


2021 ◽  
Author(s):  
Tran Hai Anh ◽  
Tran Huy Hoang ◽  
Vu Thi Ngoc Bich ◽  
Trinh Son Tung ◽  
Tran Dieu Linh ◽  
...  

Abstract Background: Multidrug-resistant bacteria including carbapenem resistant Pseudomonas aeruginosa are recognised as an important cause of hospital-acquired infections worldwide. To determine the molecular characterisation and antibiotic resistant genes associated with carbapenem-resistant P. aeruginosa. Methods: we conducted whole-genome sequencing and phylogenetic analysis of 72 carbapenem-resistant P. aeruginosa isolated from hospital-acquired infection patients from 2010 to 2015 in three major hospitals in Hanoi, Vietnam. Results: We identified three variants of IMP genes, among which IMP-15 gene was the most frequent (n= 34) in comparison to IMP-26 (n= 2) and IMP-51 (n=12). We observed two isolates with imipenem MIC >128mg/L that co-harboured IMP-15 and DIM-1 genes and seven isolates (imipenem MIC> 128mg/L) with KPC-1 gene from the same hospital. MLST data showed that sequence types (ST) of 72 isolates were classified into 18 STs and phylogenetic tree analysis divided these isolates into nine groups. Conclusion: Our results provide evidence that not only IMP-26, but other variants of IMPs like IMP-15 and IMP-51 genes and several STs (ST235, ST244, ST277, ST310, ST773 and ST3151) have been disseminated in health care settings in Vietnam. Also, we report the first finding in Vietnam that two isolates belonging to ST1240 and ST3340 harboured two important carbapenemase genes (IMP-15 and, DIM-1) and seven isolates belonging to ST3151 of P. aeruginosa carried the KPC-1 gene, which could be a potential cause of seriously restricted available treatment options in healthcare settings.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Su Jin Lee ◽  
Jueng Soo You ◽  
Amal Gharbi ◽  
Yong Joo Kim ◽  
Mi Suk Lee ◽  
...  

AbstractSepsis is caused by organ dysfunction initiated by an unrestrained host immune response to infection. The emergence of antibiotic-resistant bacteria has rapidly increased in the last decades and has stimulated a firm research platform to combat infections caused by antibiotic-resistant bacteria that cannot be eradicated with conventional antibiotics. Strategies like epigenetic regulators such as lysine demethylase (Kdm) has received attention as a new target. Thus, we sought to investigate the epigenetic mechanisms in sepsis pathophysiology with the aim of discovering new concepts for treatment. A transcriptome analysis of dendritic cells during their inflammatory state identified Kdm as a critical molecule in sepsis regulation. Next, 8-hydroxyquinoline-5-carboxylic acid (IOX1) ability to control endotoxemia induced by Lipopolysaccharide and bacterial sepsis was demonstrated. IOX1 has been shown to regulate endotoxemia and sepsis caused by Escherichia coli and carbapenem-resistant Acinetobacter baumannii and has also contributed to the suppression of multidrug-resistant bacterial growth through the inhibition of DNA Gyrase. These findings show that IOX1 could be a component agent against bacterial sepsis by functioning as a broad-spectrum antibiotic with dual effects.


Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 424
Author(s):  
Francesco Perrotta ◽  
Marco Paolo Perrini

Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health threat. Infections due to these organisms are associated with significant morbidity and mortality. Among them, metallo-β-lactamases (MBLs)-producing Klebsiella pneumoniae are of global concern today. The ceftazidime/avibactam combination and the ceftazidime/avibactam + aztreonam combination currently represent the most promising antibiotic strategies to stave off these kinds of infections. We describe the case of a patient affected by thrombotic thrombocytopenic purpura (TTP) admitted in our ICU after developing a hospital-acquired SarsCoV2 interstitial pneumonia during his stay in the hematology department. His medical conditions during his ICU stay were further complicated by a K. Pneumoniae NDM sepsis. To our knowledge, the patient had no risk factors for multidrug-resistant bacteria exposure or contamination during his stay in the hematology department. During his stay in the ICU, we treated the sepsis with a combination therapy of ceftazidime/avibactam + aztreonam. The therapy solved his septic state, allowing for a progressive improvement in his general condition. Moreover, we noticed that the negativization of the hemocultures was also associated to a decontamination of his known rectal colonization. The ceftazidime/avibactam + aztreonam treatment could not only be a valid therapeutic option for these kinds of infections, but it could also be considered as a useful tool in selected patients’ intestinal decolonizations.


2021 ◽  
Author(s):  
Anke Breine ◽  
Megane Van Gysel ◽  
Mathias Elsocht ◽  
Clemence Whiteway ◽  
Chantal Philippe ◽  
...  

Synopsis Objectives: The spread of antibiotic resistant bacteria is an important threat for human healthcare. Acinetobacter baumannii bacteria impose one of the major issues, as multidrug- to pandrug-resistant strains have been found, rendering some infections untreatable. In addition, A. baumannii is a champion in surviving in harsh environments, being capable of resisting to disinfectants and to persist prolonged periods of desiccation. Due to the high degree of variability found in A. baumannii isolates, the search for new antibacterials is challenging. Here, we screened a compound library to identify compounds active against recent isolates of A. baumannii bacteria. Methods: A repurposing drug screen was undertaken to identify A. baumannii growth inhibitors. One hit was further characterized by determining its IC50 and testing its activity on 43 recent clinical A. baumannii isolates, amongst which 40 are extensively drug- and carbapenem-resistant strains. Results: The repurposing screen led to the identification of a harmine-derived compound, called HDC1, which proved to have bactericidal activity on the multidrug-resistant AB5075-VUB reference strain with an IC50 of 48.23 [mu]M. In addition, HDC1 impairs growth of all 43 recent clinical A. baumannii isolates. Conclusions: We identified a compound with inhibitory activity on all tested, extensively drug-resistant clinical A. baumannii isolates.


mBio ◽  
2017 ◽  
Vol 8 (6) ◽  
Author(s):  
Matthew A. Crawford ◽  
Debra J. Fisher ◽  
Lisa M. Leung ◽  
Sara Lomonaco ◽  
Christine Lascols ◽  
...  

ABSTRACT The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A. Colistin-resistant K. pneumoniae isolates affected by genetic mutation of the PmrA/PmrB two-component system, a chromosomally encoded regulator of lipopolysaccharide modification, and containing 4-amino-4-deoxy-l-arabinose-modified lipid A were also found to be susceptible to chemokine-mediated antimicrobial activity. However, loss of PhoP/PhoQ autoregulatory control, caused by disruption of the gene encoding the negative regulator MgrB, limited the bactericidal effects of CXCL9 and CXCL10 in a variable, strain-specific manner. Cumulatively, these findings provide mechanistic insight into chemokine-mediated antimicrobial activity, highlight disparities amongst determinants of colistin resistance, and suggest that chemokine-mediated bactericidal effects merit additional investigation as a therapeutic avenue for treating infections caused by multidrug-resistant pathogens. IMPORTANCE As bacterial pathogens become resistant to multiple antibiotics, the infections they cause become increasingly difficult to treat. Carbapenem antibiotics provide an essential clinical barrier against multidrug-resistant bacteria; however, the dissemination of bacterial enzymes capable of inactivating carbapenems threatens the utility of these important antibiotics. Compounding this concern is the global spread of bacteria invulnerable to colistin, a polymyxin antibiotic considered to be a last line of defense against carbapenem-resistant pathogens. As the effectiveness of existing antibiotics erodes, it is critical to develop innovative antimicrobial therapies. To this end, we demonstrate that the chemokines CXCL9 and CXCL10 kill the most concerning carbapenem- and colistin-resistant pathogens. Our findings provide a unique and timely foundation for therapeutic strategies capable of countering antibiotic-resistant “superbugs.” IMPORTANCE As bacterial pathogens become resistant to multiple antibiotics, the infections they cause become increasingly difficult to treat. Carbapenem antibiotics provide an essential clinical barrier against multidrug-resistant bacteria; however, the dissemination of bacterial enzymes capable of inactivating carbapenems threatens the utility of these important antibiotics. Compounding this concern is the global spread of bacteria invulnerable to colistin, a polymyxin antibiotic considered to be a last line of defense against carbapenem-resistant pathogens. As the effectiveness of existing antibiotics erodes, it is critical to develop innovative antimicrobial therapies. To this end, we demonstrate that the chemokines CXCL9 and CXCL10 kill the most concerning carbapenem- and colistin-resistant pathogens. Our findings provide a unique and timely foundation for therapeutic strategies capable of countering antibiotic-resistant “superbugs.”


Author(s):  
Jaffar A Al-Tawfiq ◽  
Ali A Rabaan ◽  
Justin V Saunar ◽  
Ali M Bazzi

Abstract Background The molecular epidemiology of resistance of carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas aeruginosa are important in the study of multidrug-resistant bacteria. We evaluate the prevalence of the different mechanisms of CRE in a hospital in Saudi Arabia. Methods Carbapenem non-susceptible isolates of Enterobacteriaceae and Pseudomonas aeruginosa were tested by real-time PCR for the detection of genes responsible for beta-lactam resistance. Results There were a total of 200 isolates with carbapenem non-susceptibility and these were Klebsiella pneumoniae (n=96, 48%), Escherichia coli (n=51, 25.5%) and Pseudomonas aeruginosa (n=45, 22.5%). The detected carbapenemases were oxacillinase-48 (OXA-48) (n=83, 41.5%), New Delhi metallo-β-lactamase (NDM) (n=19, 2.5%) and both NDM and OXA-48 (n=5, 2.5%). The other carbapenemases were imipenemase (n=1, 0.5%), Verona integrin encoded metallo-β-lactamase (n=6, 3%) and Klebsiella pneumoniae carbapenemase (n=1, 0.5%), but none were detected in 86 isolates (43%). Conclusion The most common carbapenemases were OXA-48 and a significant percentage had no detectable genes. These data will help in the selection of new antimicrobial therapies.


10.3823/852 ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jamal Wadi Al Ramahi M.D, FIDSA ◽  
MaramAbu Said ◽  
Rasmieh Abu Kwaik ◽  
Walid Jamal ◽  
Deema Al Jammal ◽  
...  

Background To study resistance rates of multidrug-resistant bacteria (MDR) for new Cephalosporines before their widespread use in Jordan. Methods During September 2019 - May 2020, MDR-bacteria were prospectively collected from microbiology laboratories of three hospitals, susceptibility of the extended-spectrum β-lactamases-producing Enterobacteriaceae (ESBL), K. pneumoniae-carbapenemases strains (KPC), carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant P. aeruginosa (CRPa), carbapenem-resistant A. baumannii (CRAb), and Methicillin-resistant Staphylococcus aureus (MRSA) were tested. Demographic details for patients were identified. Antimicrobials evaluated were ceftazidime-avibactam, ceftolozane-tazobactam, and ceftobiprole medocaril. Results Non-duplicate 263 MDR clinical isolates were collected from sterile sites; ESBL (128), P. aeruginosa (57), MRSA (37), KPC (22), A. baumannii (11), and CRE (n = 8). The age was dominated by the older age group (Age > 64, Pearson R = 0.985, R2 = 0.969, P = 0.000). Males were 143 and females 107 (P < 0.000). There were (194) isolate from the wards and (55) were from the ICUs. Sources were urine (96), blood (36), soft tissues (49), abdomen (24), URT (14), and osteo-skeletal (12). Clinical diagnoses were: UTI (90). Bacteremia (36), SSTI (45), IAI (23), pneumonia (17), URTI (13), osteomyelitis (11), and diabetic foot (6). The susceptibility of the ESBL-producing bacteria was 100% for meropenem, 99% for ceftazidime-avibactam, and 90% for ceftolozane/tazobactam. P. aeruginosa was, 73% for ceftazidime-avibactam, 62% susceptible to ceftolozane/tazobactam, 62% for meropenem, and 45% to ceftobiprole. CRE was 38% susceptible to ceftazidime-avibactam and KPC 15%, while ceftolozane-tazobactam susceptibility was zero, and 14% for CRE, and 0% for Ceftobiprole Medocaril. A. baumannii was 13% susceptible to ceftazidime-avibactam, meropenem 9%, and 2% for ceftolozane/tazobactam Conclusion Ceftazidime-avibactam and ceftolozane/tazobactam may be useful alternatives for the treatment of ESBL-producers and P. aeruginosa, though the MDR-bacteria demonstrated some resistance to the newly introduced agents before their widespread use in the country.  


Author(s):  
Dhafer Mohammed M. Al Salah ◽  
Amandine Laffite ◽  
Periyasamy Sivalingam ◽  
John Poté

AbstractThe co-occurrence of heavy metals, antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs) from hospital effluents spreading into the river receiving systems and evaluating associated risks are topics of scientific interest and still under-studied in developing countries under tropical conditions. To understand the selectors of the ARGs, we examined the occurrence of heavy metals (Cr, Co, Ni, Cu, Cd, Pb and Zn), associated ARB (β-lactam-resistant Escherichia coli, β-lactam-resistant Enterobacteriaceae, and carbapenem-resistant Enterobacteriaceae) and ARGs (blaOXA, blaCTX-M, blaIMP, blaTEM) in water and sediments from two sub-urban rivers receiving urban and hospital effluent waters in the Democratic Republic of the Congo (DRC). High abundances of ARB and ARGs were observed in all sediment samples. All the metal contents correlated negatively with grain size (− 0.94 ≤ r ≤  − 0.54, p < 0.05) except for Ni and positively with organic matter content and total copies of 16 s rRNA (0.42 ≤ r ≤ 0.79, p < 0.05), except for Ni and Zn. The metals had a significant positive correlation with the faecal indicator Enterococcus except for Ni and Cd (0.43 ≤ r ≤ 0.67, p < 0.05). Carbapenem-resistant Enterobacteriaceae correlated negatively with Zn (r =  − 0.44, p < 0.05) and positively with all the rest of toxic metals (0.58 ≤ r ≤ 1.0, p < 0.05). These results suggested that some metals had a great influence on the persistence of ARB and ARGs in sediments. Overall, this study strongly recommends the managing urban wastewater to preserve water resources used for human and agricultural purposes. Additionally, we recommend the utilizing biological indicators (faecal indicator bacteria, ARB, ARGs) when investigating urban wastewater pollutions.


Sign in / Sign up

Export Citation Format

Share Document