scholarly journals Clinical outcomes and safety of polymyxin B in the treatment of carbapenem-resistant Gram-negative bacterial infections: a real-world multicenter study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaojuan Zhang ◽  
Shaoyan Qi ◽  
Xiaoguang Duan ◽  
Bing Han ◽  
Shuguang Zhang ◽  
...  

Abstract Background High morbidity and mortality due to carbapenem-resistant Gram-negative bacilli (CR-GNB) has led to the resurgence of polymyxin B (PMB) use in the last decade. The aim of our multicenter, real-world study was to evaluate the effectiveness and safety of PMB in the treatment of CR-GNB infections. Methods The real-world study included patients treated with intravenous PMB for at least 7 days during the period of October 2018 through June 2019. Associations between these clinical features and 28-day mortality or all-cause hospital mortality were explored through univariate analyses and multivariable logistic regression. Results The study included 100 patients. Many patients presented with combined chronic conditions, septic shock, mechanical ventilation, and the presence of Klebsiella pneumoniae. The mean duration of PMB therapy was 11 days (range 7–38 days). Temperature (38 °C vs 37.1 °C), white blood cells (14.13 × 109/l vs 9.28 × 109/l), C-reactive protein (103.55 ug/l vs 47.60 ug/l), procalcitonin (3.89 ng/ml vs 1.70 ng/ml) and APACHE II levels (17.75 ± 7.69 vs 15.98 ± 7.95) were significantly decreased after PMB treatment. The bacteria eradication rate was 77.65%. The overall mortality at discharge was 15%, and 28-day mortality was 40%. Major adverse reactions occurred in 16 patients. Nephrotoxicity was observed in 7 patients (7%). Conclusions Our results provide positive clinical and safety outcomes for PMB in the treatment of CR-GNB. Timely and appropriate use of PMB may be particularly useful in treating patients with sepsis in CR-GNB infections.

2021 ◽  
Author(s):  
Xiaojuan Zhang ◽  
Shaoyan Qi ◽  
Xiaoguang Duan ◽  
Bing Han ◽  
Shuguang Zhang ◽  
...  

Abstract Background: High morbidity and mortality due to carbapenem-resistant Gram-negative bacilli (CR-GNB) has led to the resurgence of polymyxin B (PMB) use in the last decade. The aim of our multicenter, real-world study was to evaluate the effectiveness and safety of PMB in the treatment of CR-GNB infections.Methods: The real-world study included patients treated with intravenous PMB for at least 7 days during the period of October 2018 through June 2019. Associations between these variables and 28-day mortality or all-cause hospital mortality were explored through univariate analyses and multivariable logistic regression. Results: The study included 100 patients. Many patients presented with combined chronic conditions, septic shock, mechanical ventilation, and the presence of Klebsiella pneumoniae. The mean duration of PMB therapy was 11 days (range 7–38 days). Temperature (38°C vs 37.1°C), white blood cells (14.13×109/L vs 9.28×109/L), C-reactive protein (103.55 ug/l vs 47.60 ug/l), procalcitonin (3.89 ng/ml vs 1.70 ng/ml) and APACHE Ⅱ levels (17.75 ± 7.69 vs 15.98 ± 7.95) were significantly decreased after PMB treatment. The bacteria eradication rate was 77.65%. The overall mortality at discharge was 15%, and 28-day mortality was 40%. Major adverse reactions occurred in 16 patients. Nephrotoxicity was observed in 7 patients (7%).Conclusions: Our results provide positive clinical and safety outcomes for PMB in the treatment of CR-GNB. Timely and appropriate use of PMB may be particularly useful in treating patients with sepsis in CR-GNB infections.


2020 ◽  
Author(s):  
Xiaojuan Zhang ◽  
Shaoyan Qi ◽  
Xiaoguang Duan ◽  
Bing Han ◽  
Shuguang Zhang ◽  
...  

Abstract Background: High morbidity and mortality due to carbapenem-resistant Gram-negative bacilli (CRGNB) was a challenge for clinicians has led to the resurgence of polymyxin B (PMB) use in the last decade. The goal of our multicenter, real-world study was to evaluate the efficacy and safety of PMB in the treatment of CRGNB.Methods: The real-world study included the patients with intravenous PMB at least 7 days during the period of October 2018 to June 2019. Data was collected from electronic patients register and follow-up. The primary outcome was 28-day mortality, the secondary outcomes included hospital mortality, occurrence of adverse events during PMB therapy. Associations between these variables and 28-day mortality or all-cause hospital mortality were explored through univariate analyses and multivariable logistic regression. At the same time, therapeutic effects were observed. Results: The study included 100 patients. There were 39% presence of septic shock, 49% need mechanical ventilation at the beginning of therapy. The infection and condition improved after 7 days of PMB treatment. The major adverse reactions occurred in 16 cases (16%). The overall 28-day mortality was 40%. In terms of clinical characteristics, mean Sequential Organ Failure Assessment (6.77 versus 9.25,P = 0.004),mean Acute Physiology and Chronic Health Evaluation II (APACHEII) scores (16.17 versus 19.78, P = 0.016) and the number of patient with mechanical ventilation (21 versus 30, P = 0.000) or septic shock (17 versus 32, P = 0.000) were lower in survivors group than nonsurvivors group. The mortality of 85 patients with identify pathogens was 38.82%, while the mortality of patients with negative pathogen culture results was 46.67% (P = 0.580). Multivariate analysis showed that mechanical ventilation (P = 0.023, OR = 3.5; CI: 1.194–10.739), septic shock (P = 0.002, OR = 5.960; CI: 1.923–18.473) were associated with 28-day mortality.Conclusion: Our research found that PMB may be as effective and safe as standard antibiotics for the treatment of CRGNB. Timely and appropriate use of PMB will have a positive impact on the clinical outcomes of patients with sepsis in CRGNB.


Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 451
Author(s):  
Yiying Cai ◽  
Hui Leck ◽  
Ray W. Tan ◽  
Jocelyn Q. Teo ◽  
Tze-Peng Lim ◽  
...  

Population pharmacokinetic studies have suggested that high polymyxin B (PMB) doses (≥30,000 IU/kg/day) can improve bacterial kill in carbapenem-resistant Gram-negative bacteria (CR-GNB). We aim to describe the efficacy and nephrotoxicity of patients with CR-GNB infections prescribed high-dose PMB. A single-centre cohort study was conducted from 2013 to 2016 on septic patients with CR-GNB infection and prescribed high-dose PMB (~30,000 IU/kg/day) for ≥72 h. Study outcomes included 30-day mortality and acute kidney injury (AKI) development. Factors associated with AKI were identified using multivariable regression. Forty-three patients with 58 CR-GNB received high-dose PMB; 57/58 (98.3%) CR-GNB were susceptible to PMB. The median daily dose and duration of high-dose PMB were 32,051 IU/kg/day (IQR, 29,340–34,884 IU/kg/day) and 14 days (IQR, 7–28 days), respectively. Thirty-day mortality was observed in 7 (16.3%) patients. AKI was observed in 25 (58.1%) patients with a median onset of 8 days (IQR, 6–13 days). Higher daily PMB dose (aOR,1.01; 95% CI, 1.00–1.02) and higher number of concurrent nephrotoxins (aOR, 2.14; 95% CI; 1.03–4.45) were independently associated with AKI. We observed that a sizable proportion developed AKI in CR-GNB patients described high-dose PMB; hence, the potential benefits must be weighed against increased AKI risk. Concurrent nephrotoxins should be avoided to reduce nephrotoxicity.


Author(s):  
Sara Alosaimy ◽  
Abdalhamid M Lagnf ◽  
Taylor Morrisette ◽  
Marco R Scipione ◽  
Jing J Zhao ◽  
...  

Abstract Background We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of Gram-negative infections (GNI), primarily including carbapenem-resistant Enterobacterales (CRE). Methods This is a real-world, multi-center, retrospective cohort within the United States between 2017-2020. Adult patients who received MEV for ≥ 72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCO) and was examined by multivariable logistic regression analysis (MLR). Results Overall, 126 patients were evaluated from 13 medical centers within ten states. The most common infection source were respiratory tract (38.1%) and intraabdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in four patients; nephrotoxicity (n=2), hepatoxicity (n=1), and rash (n=1). CART-BP between early and delayed treatment was 48 hours (P=0.04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (aOR=0.277, [0.081 – 0.941]). Conclusion Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNI, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCO.


2020 ◽  
Vol 7 (3) ◽  
Author(s):  
Sara Alosaimy ◽  
Sarah C J Jorgensen ◽  
Abdalhamid M Lagnf ◽  
Sarah Melvin ◽  
Ryan P Mynatt ◽  
...  

Abstract Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV.


Author(s):  
Brigitte Rina Aninda Sidharta ◽  
JB. Suparyatmo ◽  
Avanti Fitri Astuti

Invasive Fungal Infections (IFIs) can cause serious problems in cancer patients and may result in high morbidity andmortality. C-reactive protein levels increase in response to injury, infection, and inflammation. C-reactive protein increasesin bacterial infections (mean of 32 mg/L) and in fungal infections (mean of 9 mg/L). This study aimed to determineC-Reactive Protein (CRP) as a marker of fungal infections in patients with acute leukemia by establishing cut-off values ofCRP. This study was an observational analytical study with a cross-sectional approach and was carried out at the Departmentof Clinical Pathology and Microbiology of Dr. Moewardi Hospital in Surakarta from May until August 2019. The inclusioncriteria were patients with acute leukemia who were willing to participate in this study, while exclusion criteria were patientswith liver disease. There were 61 samples consisting of 30 male and 31 female patients with ages ranging from 1 to 70 years.Fifty-four patients (88.5%) were diagnosed with Acute Lymphoblastic Leukemia (ALL) and 30 (49.18%) were in themaintenance phase. The risk factors found in those patients were neutropenia 50-1500 μL (23.8%), use of intravenous line(22%), and corticosteroid therapy for more than one week (20.9%). The median of CRP in the group of patients with positiveculture results was 11.20 mg/L (11.20-26.23 mg/L) and negative culture results in 0.38 mg/L (0.01-18.63 mg/L). The cut-offvalue of CRP using the Receiver Operating Curve (ROC) was 9.54 mg/L (area under curve 0.996 and p. 0.026), with a sensitivityof 100%, specificity of 93.2%, Positive Predictive Value (PPV) of 33.3%, Negative Predictive Value (PPV) of 100%, PositiveLikelihood Ratio (PLR) of 1.08, Negative Likelihood Ratio (NLR) of 0 and accuracy of 93.4%. C-reactive protein can be used asa screening marker for fungal infections in patients with acute leukemia.


Author(s):  
Hari P. Nepal ◽  
Rama Paudel

Carbapenems are beta-lactam drugs that have broadest spectrum of activity. They are commonly used as the drugs of last resort to treat complicated bacterial infections. They bind to penicillin binding proteins (PBPs) and inhibit cell wall synthesis in bacteria. Important members that are in clinical use include doripenem, ertapenem, imipenem, and meropenem. Unlike other members, imipenem is hydrolyzed significantly by renal dehydropeptidase; therefore, it is administered together with an inhibitor of renal dehydropeptidase, cilastatin. Carbapenems are usually administered intravenously due to their low oral bioavailability. Most common side effects of these drugs include nausea, vomiting, diarrhea, skin rashes, and reactions at the infusion sites. Increasing resistance to these antibiotics is being reported throughout the world and is posing a threat to public health.  Primary mechanisms of carbapenem resistance include expulsion of drug and inactivation of the drug by production of carbapenemases which may not only hydrolyze carbapenem, but also cephalosporin, penicillin, and aztreonam. Resistance especially among Gram negative bacteria is of much concern since there are only limited therapeutic options available for infections caused by carbapenem resistant Gram-negative bacterial pathogens. Commonly used drugs to treat such infections include polymyxins, fosfomycin and tigecycline.


1993 ◽  
Vol 39 (2) ◽  
pp. 293-297 ◽  
Author(s):  
T Nakayama ◽  
S Sonoda ◽  
T Urano ◽  
T Yamada ◽  
M Okada

Abstract We examined serum amyloid protein A (SAA) and C-reactive protein (CRP) as inflammatory markers of viral and bacterial infections. Both acute-phase reactants increased in the acute stage and thereafter decreased in the convalescent stage. In viral infections, the mean serum concentrations of SAA during the acute stage were 141 mg/L in infections with adenovirus, 77 mg/L with measles virus, 63 mg/L with influenza virus, 55 mg/L with parainfluenza virus, 31 mg/L with respiratory syncytial virus, and 31 mg/L in aseptic meningitis. The mean serum concentration of CRP was 19 mg/L for adenovirus infection and < 7 mg/L in all other viral infections. The SAA concentrations were 5- to 11-fold greater than the CRP concentrations. Both the SAA and the CRP concentrations were higher in bacterial infections than in viral infections. Changes in the concentrations of serum SAA paralleled those in serum CRP in bacterial infection; during the course of viral infection, however, serum SAA tended to disappear more quickly than CRP did. SAA appears to be a clinically useful marker of inflammation in acute viral infections, with or without significant changes in the CRP concentration.


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