Objective: Analysis and investigation of pathogenic characteristics of polymyxin-and carbapenem-resistant Klebsiella pneumoniae (PR-CRKP). Methods: A total of 23 PR-CRKP strains isolated from clinical specimens from the General Hospital of Southern Theater Command from March 2019 to July 2021 were retrospectively collected, Whole-genome sequencing was performed on 23 PR-CRKP strains, resistance genes were identified by comparison of the CARD and the ResFinder database, high-resolution typing of PR-CRKP strains was analyzed by core genomic multilocus sequencing (cgMLST) and single nucleotide polymorphism (SNP); polymyxin resistance genes were determined by PCR and sequencing. Results: All PR-CRKP strains were KPC-2 producing ST11 types. cgMLST results showed that the evolutionary distance between the PR-CRKP strains and Klebsiella pneumoniae in mainland China was 66.44 on average, which is more closely related than foreign strains; the 23 PR-CRKP strains were divided into 3 main subclusters based on SNP phylogenetic trees, with some aggregation among Clade 2-1 in the isolation department and date. The two-component negative regulatory gene mgrB has seven mutation types including point mutations, different insertion fragments and different insertion positions. Conclusion: The close affinity of PR-CRKP strains indicate the possibility of nosocomial clonal transmission and the need to strengthen surveillance of PR-CRKP strains to prevent epidemic transmission of PR-CRKP.
Humans ; Carbapenems/pharmacology* ; Anti-Bacterial Agents/therapeutic use* ; Klebsiella pneumoniae/genetics* ; Polymyxins/pharmacology* ; beta-Lactamases ; Phylogeny ; Retrospective Studies ; Multilocus Sequence Typing ; Microbial Sensitivity Tests

Aims: Polymyxins are an important last-line treatment for infections caused by multidrug-resistant Gram-negative bacteria. Nonetheless, the emergence of polymyxin-resistance and the limiting of polymyxin monotherapy urgently demands its optimisation. Aquilaria malaccensis (Agarwood) has been widely used as traditional medicine. Many parts of the plant including leaves exhibit a considerable in vitro antibacterial activity against microbial pathogens. Exploiting A. malaccensis in combination with polymyxins provides a novel strategy in fighting antimicrobial resistance. The objective of this study was to evaluate the combination effects of A. malaccensis extract with polymyxins against Acinetobacter baumannii and Klebsiella pneumoniae. Methodology and results: In vitro time-kill studies and GC-MS analysis were performed to evaluate the bacterial killing of polymyxin B and extract combination and analyse chemical compounds of the extract, respectively. The combination of polymyxin B (1 mg/L) and A. malaccensis extract (32 mg/mL and 64 mg/mL) treatments exhibited enhanced bacterial killing compared to polymyxin B alone at 4 h and 24 h. Combination treatments also inhibited the bacterial growth of both A. baumannii and K. pneumoniae observed throughout the 24 h. More than sixty compounds including phytol, 9,12-octadecadienal, fatty acid, alkanes and terpenoids were putatively identified as the compounds that likely contributed to the antibacterial activity. Conclusion, significance and impact of study This study was the first to report the potential application of A. malaccensis extract in combination with polymyxin B in treatment against A. baumannii and K. pneumoniae and can be further investigated and optimized for the treatment of bacterial infectious diseases.
Thymelaeaceae ; Polymyxins ; Acinetobacter baumannii--immunology ; Klebsiella pneumoniae--immunology

The current strategy in treating multi-drug resistant gram-negative bacterial (MDR-GNB) infections is salvage therapy by using polymyxins. However, the beginning emergence of polymyxin resistance should enforce strict antimicrobial stewardship programs to preserve polymyxin efficacy. Knowledge of structural characteristics, pharmacodynamic, and pharmacokinetic profiles of polymyxins, as well as consideration of efficacy, safety, suitability, and cost, will help in the choice of the appropriate polymyxin for therapy. Polymyxin B is the recommended polymyxin for systemic use, while colistin is recommended for lower urinary tract infections, intraventricular, and intrathecal use. Either polymyxin can be used for hospital-acquired and ventilator-associated pneumonia. Combination therapy over monotherapy remains to be advantageous due to synergism and decreased resistance development. The choice of the second drug to be used should be based on full susceptibility, or if unavailable, a drug with the least minimum inhibitory concentration relative to the breakpoint set by the Clinical and Laboratory Standards Institute. Using the mnemonic ESCAPE can also guide physicians in their polymyxin prescription process: (1) Checking if the pathogen is Extensively resistant or multi-drug resistant; (2) checking the patient’s clinical status if compatible with Significant infection; (3) using Combination therapy; (4) ensuring Adequate dosing; (5) Proper preparation and administration of drug; and (6) keeping an Eye for response and adverse effects.
Polymyxin B ; Colistin ; Polymyxins

Carbapenem-resistant Enterobacteriaceae (CRE) are now spread worldwide. In Korea, the number of CRE isolation is rapidly increasing, and impending endemicity is a concern. To cope well with CRE, thorough infection control, such as active surveillance, early detection, strict contact precaution, cleaning the environment, and antibiotic stewardship is very important. Therapeutic options include polymyxin, tigecycline, fosfomycin or the combination of them with carbapenem, which is currently the mainstay of treatment. In addition, various combination regimens with new carbapenemase inhibitors such as avibactam, vaborbactam, or relebactam, and other classes of antimicrobials such as plazomicin and siderophore cephalosporin are in the process of evaluation.
Carbapenems ; Enterobacteriaceae* ; Fosfomycin ; Infection Control ; Korea ; Polymyxins

Although shock in sepsis is usually managed successfully by conventional medical treatment, a subset of cases do not respond and may require salvage therapies such as veno-arterial extracorporeal membrane oxygenation (VA ECMO) support as well as an attempt to remove endotoxins. However, there are limited reports of attempts to remove endotoxins in patients with septic shock on VA ECMO support. We recently experienced a case of septic shock with severe myocardial injury whose hemodynamic improvement was unsatisfactory despite extracorporeal membrane oxygenation (ECMO) support. Since the cause of sepsis was acute pyelonephritis and blood cultures grew gram-negative bacilli, we additionally applied polymyxin B direct hemoperfusion (PMX-DHP) to the ECMO circuit and were able to successfully taper off vasopressors and wean off ECMO support. To the best of our knowledge, this is the first adult case in which PMX-DHP in addition to ECMO support was successfully utilized in a patient with septic shock. This case indicates that additional PMX-DHP therapy may be beneficial and technically feasible in patients with septic shock with severe myocardial injury refractory to ECMO support.
Adult ; Cardiomyopathies* ; Endotoxins ; Extracorporeal Membrane Oxygenation ; Hemodynamics ; Hemoperfusion* ; Humans ; Membranes* ; Oxygen* ; Polymyxin B* ; Polymyxins* ; Pyelonephritis ; Salvage Therapy ; Sepsis ; Shock ; Shock, Septic*

Although shock in sepsis is usually managed successfully by conventional medical treatment, a subset of cases do not respond and may require salvage therapies such as veno-arterial extracorporeal membrane oxygenation (VA ECMO) support as well as an attempt to remove endotoxins. However, there are limited reports of attempts to remove endotoxins in patients with septic shock on VA ECMO support. We recently experienced a case of septic shock with severe myocardial injury whose hemodynamic improvement was unsatisfactory despite extracorporeal membrane oxygenation (ECMO) support. Since the cause of sepsis was acute pyelonephritis and blood cultures grew gram-negative bacilli, we additionally applied polymyxin B direct hemoperfusion (PMX-DHP) to the ECMO circuit and were able to successfully taper off vasopressors and wean off ECMO support. To the best of our knowledge, this is the first adult case in which PMX-DHP in addition to ECMO support was successfully utilized in a patient with septic shock. This case indicates that additional PMX-DHP therapy may be beneficial and technically feasible in patients with septic shock with severe myocardial injury refractory to ECMO support.
Adult ; Cardiomyopathies ; Endotoxins ; Extracorporeal Membrane Oxygenation ; Hemodynamics ; Hemoperfusion ; Humans ; Membranes ; Oxygen ; Polymyxin B ; Polymyxins ; Pyelonephritis ; Salvage Therapy ; Sepsis ; Shock ; Shock, Septic

Severe sepsis and septic shock are the main causes of death in critically ill patients. Early detection and appropriate treatment according to guidelines are crucial for achieving favorable outcomes. Endotoxin is considered to be a main element in the pathogenic induction of gram-negative bacterial sepsis. Polymyxin B hemoperfusion can remove endotoxin and is reported to improve clinical outcomes in patients with intra-abdominal septic shock, but its clinical efficacy for pneumonic septic shock remains unclear. Here, we report a case of a 51-year-old man with pneumonic septic shock caused by Pseudomonas aeruginosa, who recovered through polymyxin B hemoperfusion.
Cause of Death ; Critical Illness ; Gram-Negative Bacteria* ; Hemoperfusion* ; Humans ; Middle Aged ; Polymyxin B* ; Polymyxins* ; Pseudomonas aeruginosa ; Sepsis ; Shock, Septic*

Severe sepsis and septic shock are the main causes of death in critically ill patients. Early detection and appropriate treatment according to guidelines are crucial for achieving favorable outcomes. Endotoxin is considered to be a main element in the pathogenic induction of gram-negative bacterial sepsis. Polymyxin B hemoperfusion can remove endotoxin and is reported to improve clinical outcomes in patients with intra-abdominal septic shock, but its clinical efficacy for pneumonic septic shock remains unclear. Here, we report a case of a 51-year-old man with pneumonic septic shock caused by Pseudomonas aeruginosa, who recovered through polymyxin B hemoperfusion.
Cause of Death ; Critical Illness ; Gram-Negative Bacteria ; Hemoperfusion ; Humans ; Middle Aged ; Polymyxin B ; Polymyxins ; Pseudomonas aeruginosa ; Sepsis ; Shock, Septic

The prevalence of carbapenem-resistant gram-negative bacterial pathogens (CRGNs) has increased dramatically during the last 10 years, but the optimal treatment for CRGN infections is not well established due to the relative scarcity of robust clinical data. The polymyxins remain the most consistently active agents against CRGNs in vitro. Tigecycline, based on its in vitro antibacterial spectrum, could also be considered as a therapeutic option in the treatment of infections caused by certain CRGNs. Other agents, including aminoglycosides, rifampin, trimethoprim-sulfamethoxazole, fosfomycin and fluoroquinolones, could be considered as monotherapy or combination therapy against CRGNs in appropriate contexts, as combination therapy with two or more in vitro active drugs appears to be more effective than monotherapy based on some clinical data. Several promising new agents are in late-stage clinical development, including ceftolozane-tazobactam, ceftazidime-avibactam and plazomicin. Given the shortage of adequate treatment options, containment of CRGNs should be pursued through implementation of adequate infection prevention procedures and antimicrobial stewardship to reduce the disease burden and prevent future outbreaks of CRGNs.
Aminoglycosides ; Colistin ; Containment of Biohazards ; Disease Outbreaks ; Drug Therapy, Combination ; Fluoroquinolones ; Fosfomycin ; Polymyxins ; Prevalence ; Rifampin ; Trimethoprim, Sulfamethoxazole Drug Combination

OBJECTIVETo study the characteristics of community-acquired urinary tract infections (CAUTIs) in children, analyze the risk factors and the susceptibility of antibiotics, thus to provide references to the diagnosis and medication of Pseudomonas aeruginosa (PA)-CAUTIs. Mothod Totally 22 cases of PA-CAUTIs were selected in one hospital from Jan, 2006 to Jan, 2012, their clinical information, laboratory results and radiological images were collected, and were compared with the CAUTIs cased by E. coli of those randomly selected over the same period.

RESULTIn those 22 cases with PA-CAUTIs, the mean value of protein level was (32.25 ± 13.81) mg/ml, 19 of them were hospitalized, 6 had urinary operation history, 7 of them had long-term usage of glucocorticoids or immunosuppressive agents, and 20 had underlying diseases. A total of 22 children with 26 PA-CAUTIs episodes were compared to E. coli-CAUTIs. Compared with E. coli-CAUTIs patients, children with PA-CAUTIs more often presented with a lower albumin (P = 0.017), a history of urinary operation(P = 0.03), more cases had a history of urinary operation (P = 0.03), a long-term usage of glucocorticoids or immunosuppressive medication (P = 0.044). Through multivariate logistic regression of variables that were significant in univariate analysis (with hospitalizations, long-term usage of glucocorticoids or immunosuppressive, albumin, underlying disease and urinary operation histories), and it turned out that underlying diseases (odds ratio 8.500, 95% CI 1.513 - 47.761, P = 0.037) and with urinary operation histories (odds ratio 6.196, 95% CI 1.120 - 34.273, P = 0.037) were proved as the independent risk factors for PA-CAUTIs. Those PA bacterial strains had a 36.36% resistance rate to piperacillin, aztreonam and gentamicin, a 31.82% resistance rate to cefepime and ceftazidime, while the resistance rate (4.55%) to carbapenem antibiotics was relatively low, only to bacillosporin all the strains were sensitive.

CONCLUSIONUnderlying diseases and the urinary operation histories are the independent risk factors of the occurrence of PA-CAUTIs, carbapenem antibiotics and bacillosporin can be considered as the drugs of choice for its treatment.

Anti-Bacterial Agents ; therapeutic use ; Case-Control Studies ; Child ; Child, Preschool ; Community-Acquired Infections ; drug therapy ; epidemiology ; pathology ; Drug Resistance, Bacterial ; Escherichia coli ; drug effects ; Escherichia coli Infections ; drug therapy ; epidemiology ; pathology ; Female ; Humans ; Male ; Polymyxins ; therapeutic use ; Pseudomonas Infections ; drug therapy ; epidemiology ; pathology ; Pseudomonas aeruginosa ; drug effects ; Risk Factors ; Urinary Tract Infections ; drug therapy ; epidemiology ; pathology