scholarly journals The effect of double-carbapenem therapy on mortality rates and microbiological cure rates in patients diagnosed with carbapenem-resistant Klebsiella pneumoniae infections in comparison to monotherapy and currently used combinations of antibiotics

2021 ◽  
Vol 5 (1) ◽  
pp. e000243
Author(s):  
Rhiannon Olivia Moody

Introduction: Infection with the bacteria carpamenease-producing Klebsiella pneumoniae represents a significant cause of mortality in hospitalised patients. These multidrug resistant bacteria are resistant to currently used antibiotics as a result of carbapenemase production. Dual carbapenem therapy has been proposed as a valid therapeutic option, this therapy combines two carbapenem antibiotics, with one acting as a suicide inhibitor allowing the subsequent carbapenem to exert a bactericidal effect. Aim: The aim of this meta-analysis was to determine if dual carbapenem therapy had a significant effect on mortality rate and microbiological cure rate in patients diagnosed with carbapenemase-producing Klebsiella pneumoniae infections in comparison to standard antibiotic therapies. Methods: The search terms “(dual OR double) carbapenem (therapy OR treatment) AND klebsiella pneumoniae” were used to search databases and inclusion and exclusion criteria were applied to retrieved papers, a total of seven studies were identified for inclusion in the meta-analysis. The quality of included studies was assessed using the cochrane tool for risk of bias assessment and funnel plots were produced to determine the influence of publication bias. A random effects model was used to assess the outcomes; mortality rate and microbiological cure rate. Results and Conclusion: Dual carbapenem therapy had a time dependent effect on patient mortality rates. Dual carbapenem therapy significantly lowered  mortality rates in patients in comparison to standard antibiotic therapy, especially in comparison to monotherapy treatment regimens. Additionally, dual carbapenem therapy significantly improved microbiological cure rate in patients when compared to standard antibiotic treatment regimens demonstrating the possible clinical applications of a dual carbapenem antibiotic regimen in the treatment of carbapenemase-producing Klebsiella pneumoniae infections. 

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2019-214054
Author(s):  
Lara Montes-Andujar ◽  
Elena Tinoco ◽  
Orville Baez-Pravia ◽  
Carlos Martin-Saborido ◽  
Pablo Blanco-Schweizer ◽  
...  

ObjectiveThe main aim of this network meta-analysis is to identify the empiric antibiotic (Em-ATB) with the highest probability of being the best (HPBB) in terms of (1) cure rate and (2) mortality rate in hospitalised patients with community acquired pneumonia (CAP) .MethodInclusion criteria: (1) adult patients (>16 years old) diagnosed with CAP that required hospitalisation; (2) randomised to at least two different Em-ATBs, (3) that report cure rate and (4) are written in English or Spanish. Exclusion criteria: (1) ambiguous antibiotics protocol and (2) published exclusively in abstract or letter format. Data sources: Medline, Embase, Cochrane and citation reviews from 1 January 2000 to 31 December 2018. Risk of bias: Cochrane’s tool. Quality of the systematic review (SR): A MeaSurement Tool to Assess systematic Reviews-2. Certainity of the evidence: Grading of Recommendations Assessment, Development and Evaluation. Statistical analyses: frequentist method performed with the ‘netmeta’ library, R package.Results27 randomised controlled trials (RCTs) from the initial 41 307 screened citations were included. Regarding the risk of bias, more than one quarter of the studies presented low risk and no study presented high risk in all domains. The SR quality is moderate. For cure, two networks were constructed. Thus, two Em-ATBs have the HPBB: cetaroline 600 mg (two times a day) and piperacillin 2000 mg (two times a day). For mortality, three networks were constructed. Thus, three Em-ATBs have the HPBB: ceftriaxone 2000 mg (once a day) plus levofloxacin 500 (two times a day), ertapenem 1000 mg (two times a day) and amikacin 250 mg (two times a day) plus clarithromycin 500 mg (two times a day). The certainity of evidence for each results is moderate.ConclusionFor cure rate, ceftaroline and piperaciline are the options with the HPBB. However, for mortality rate, the options are ceftriaxone plus levofloxacin, ertapenem and amikacin plus clarithromycin. It seems necessary to conduct an RCT that compares treatments with the HPBB for each event (cure or mortality) (CRD42017060692).


2021 ◽  
Vol 12 ◽  
Author(s):  
Clement Yaw Effah ◽  
Emmanuel Kwateng Drokow ◽  
Clement Agboyibor ◽  
Shaohua Liu ◽  
Emmanuel Nuamah ◽  
...  

Background: Carbapenemase-producing Klebsiella pneumoniae (CpKP) has been implicated as an increasing threat to public health. CpKP is a ubiquitous, opportunistic pathogen that causes both hospital and community acquired infections. This organism hydrolyzes carbapenems and other β-lactams and thus, leading to multiple resistance to these antibiotics. Despite the difficult to treat nature of infections caused by CpKP, little has been discussed on the mortality, clinical response and microbiological success rates associated with various antibiotic regimen against CpKP. This meta-analysis was designed to fill the paucity of information on the clinical impact of various antibiotic therapeutic regimens among patients infected with CpKP.Materials and Methods: Literature in most English databases such as Medline through PubMed, Google Scholar, Web of Science, Cochrane Library and EMBASE, were searched for most studies published between the years 2015–2020. Data were analyzed using the R studio 2.15.2 statistical software program (metaphor and meta Package, Version 2) by random-effects (DerSimonian and Laird) model.Results: Twenty-one (21) studies including 2841 patients who had been infected with CpKP were analysed. The overall mortality rate was 32.2% (95%CI = 26.23–38.87; I2 = 89%; p-value ≤ 0.01, Number of patients = 2716). Pooled clinical and microbiological success rates were 67.6% (95%CI = 58.35–75.64, I2 = 22%, p-value = 0.25, Number of patients = 171) and 74.9% (95%CI = 59.02–86.09, I2 = 53%, p-value = 0.05, Number of patients = 121), respectively. CpKP infected patients treated with combination therapy are less likely to die as compared to those treated with monotherapy (OR = 0.55, 95%CI = 0.35–0.87, p-value = 0.01, Number of patients = 1,475). No significant difference existed between the mortality rate among 60years and above patients vs below 60years (OR = 0.84, 95%CI = 0.28–2.57, p-value = 0.76, 6 studies, Number of patients = 1,688), and among patients treated with triple therapy vs. double therapy (OR = 0.50, 95%CI = 0.21–1.22, p-value = 0.13, 2 studies, Number of patients = 102). When compared with aminoglycoside-sparing therapies, aminoglycoside-containing therapies had positive significant outcomes on both mortality and microbiological success rates.Conclusion: New effective therapies are urgently needed to help fight infections caused by this organism. The effective use of various therapeutic options and the strict implementation of infection control measures are of utmost importance in order to prevent infections caused by CpKP. Strict national or international implementation of infection control measures and treatment guidelines will help improve healthcare, and equip governments and communities to respond to and prevent the spread of infectious diseases caused by CpKP.


2020 ◽  
pp. 088506662095759
Author(s):  
Stewart G. Albert ◽  
Sujata Sitaula

Purpose: Etomidate causes adrenal insufficiency. Yet in critically ill patients, it is controversial whether it increases mortality rates above that of comparator anesthetic induction agents. We postulated that etomidate would increase relative mortality rates correspondingly to the severity of illness as defined by SAPS or APACHE scores. Materials and Methods: A literature search was performed on Pub Med, SCOPUS, and Cochrane Reviews for human studies, regardless of language, between 1983 and February 2020. The search strategy used keywords, “etomidate,” “adrenal insufficiency,” “glucocorticoid,” and “intensive care.” Both authors reviewed electronic data search titles, abstracts and extracted data, which were checked by the other reviewer. Primary outcome was 28-day survival. Secondary outcome was adrenal insufficiency. Results: There were 29 trials of etomidate versus comparators in 8584 patients. Etomidate was associated with adrenal insufficiency (risk ratio (rr) = 1·54, 95% CI; 1·42, 1·67, p < 0.001) and increased overall relative mortality rates (rr = 1.09, CI;1.04,1.16, p = 0.001). Meta-regression showed that with etomidate there was a continuous progressive relative risk of mortality associated with increasing severity of illness (predefined in each article by standard critical illness scores). In those patients who had a predicted mortality rate > the median for this analysis (predicted mortality 44%) the relative mortality rate (rr) = 1.20, Ci;1.12,1.29, p < 0.001, the absolute risk difference (rd) = 0.08, CI;0.05,0.11, p < 0.0001 and the number needed to harm (1/rd) was 12.5. In those with a calculated predicted mortality <44% there was no increase in relative mortality rate. Conclusions: Whereas etomidate causes adrenal insufficiency, it was not shown to increase mortality in many analyzed here in ICU settings. However, etomidate associated relative mortality rates increased progressively and correlated with the severity of critical illness scores. Intensivists should anticipate the need for glucocorticoid supplementation after etomidate in those with severe critical illness and in those with acute deterioration of vital signs.


Author(s):  
Liang-Fu Chen ◽  
Ting-Cheng Wang ◽  
Fu-Lun Chen ◽  
Shih-Chang Hsu ◽  
Chin-Wang Hsu ◽  
...  

Abstract Background Chlamydia trachomatis infection is the most common sexually transmitted infectious disease and carries a risk of complications. However, the optimal treatment for rectal chlamydial infection remains unclear. Objectives To compare the efficacy of doxycycline and azithromycin for the treatment of rectal chlamydia by undertaking a systematic review and meta-analysis of published data. Methods We searched PubMed, EMBASE, Cochrane Library, Web of Science and clinicaltrials.gov databases from inception to 7 July 2021 for randomized controlled trials (RCTs) and observational studies that compared the efficacy of doxycycline and single-dose azithromycin on rectal chlamydia cure rates. Data were synthesized using a random-effects model, and subgroup analysis was conducted. Results All included studies were conducted in developed countries. Two RCTs and nine observational studies, with a total of 2457 patients, were analysed. Doxycycline had a higher microbiological cure rate than azithromycin (risk ratio = 1.21; 95% CI = 1.15–1.28; P &lt; 0.05). Pooled results from two RCTs also revealed a higher microbiological cure rate for doxycycline than azithromycin (risk ratio = 1.27; 95% CI = 1.20–1.35; P &lt; 0.05). The results remained consistent in subgroups of different study designs, countries and sexes. Conclusions On the basis of our findings, we recommend doxycycline rather than azithromycin as a first-line treatment for rectal chlamydia in developed countries. More RCTs from developing countries are warranted.


1999 ◽  
Vol 35 (5) ◽  
pp. 384-391 ◽  
Author(s):  
ME Reimer ◽  
GC Troy ◽  
LD Warnick

Survival times and mortality rates in dogs with idiopathic immune-mediated hemolytic anemia (IMHA) have been infrequently reported in the literature. This study evaluates survival and mortality in a large group of dogs with IMHA. The association of age, sex, and breed with IMHA was evaluated by comparing affected dogs to control dogs admitted to the hospital during the same time period. Treatment regimens were reviewed to determine the effects of different agents upon survival of dogs with IMHA during hospitalization and after discharge. Median survival times for each treatment group were 57 days (prednisone), 28 days (prednisone, cyclophosphamide), 974 days (prednisone, azathioprine), 15 days (prednisone, cyclophosphamide, azathioprine), and one day (no treatment). Overall mortality rate in the population of dogs studied was 70%. Twenty-nine (41.4%) dogs either died or were euthanized while hospitalized. Forty-one (59%) dogs were discharged from the hospital. Of the dogs discharged, 10 died within the first month, another five died within three months, and another five died within a year of discharge due to assumed complications of therapy or relapses of IMHA.


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):  
Hyung Jung Oh ◽  
In Kyung Min ◽  
Yun Ho Roh ◽  
Jung ho Kim ◽  
Jin Young Ahn ◽  
...  

Abstract Background; Acute kidney injury (AKI) is the most frequent complication seen in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy (RRT) is standard care for patients with severe septic AKI, the optimal timing of RRT initiation remains controversial.Methods; The PubMed, Cochrane, and Embase databases were searched from their inception to June 2021 to identify the ideal timing of RRT initiation in patients with septic AKI by comparing 28- and 90-day mortality rates.Results; Among a total of six studies including 1,058 patients, the 28-day mortality rate was significantly lower in the early RRT-treated group compared to the late group [RR=0.69; 95% CI (0.51-0.94); P=0.018]. Moreover, among the five studies including 938 patients, the 90-day mortality rate was also significantly lower in the early RRT-treated group than the late group [RR=0.61; 95% CI (0.47-0.80); P=0.01]. In a subgroup analysis for continuous RRT (CRRT), we also found significantly lower 28- and 90-day mortality rates in the early CRRT-treated group compared to the late group.Conclusion; This study showed that early initiation of RRT might reduce 28- and 90-day mortality compared with late initiation in septic AKI patients.


2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Femke Nawijn ◽  
Diederik P. J. Smeeing ◽  
Roderick M. Houwert ◽  
Luke P. H. Leenen ◽  
Falco Hietbrink

Abstract Background Although the phrase “time is fascia” is well acknowledged in the case of necrotizing soft tissue infections (NSTIs), solid evidence is lacking. The aim of this study is to review the current literature concerning the timing of surgery in relation to mortality and amputation in patients with NSTIs. Methods A systematic search in PubMed/MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Controlled Register of Trials (CENTRAL) was performed. The primary outcomes were mortality and amputation. These outcomes were related to the following time-related variables: (1) time from onset symptoms to presentation; (2) time from onset symptoms to surgery; (3) time from presentation to surgery; (4) duration of the initial surgical procedure. For the meta-analysis, the effects were estimated using random-effects meta-analysis models. Result A total of 109 studies, with combined 6051 NSTI patients, were included. Of these 6051 NSTI patients, 1277 patients died (21.1%). A total of 33 studies, with combined 2123 NSTI patients, were included for quantitative analysis. Mortality was significantly lower for patients with surgery within 6 h after presentation compared to when treatment was delayed more than 6 h (OR 0.43; 95% CI 0.26–0.70; 10 studies included). Surgical treatment within 6 h resulted in a 19% mortality rate compared to 32% when surgical treatment was delayed over 6 h. Also, surgery within 12 h reduced the mortality compared to surgery after 12 h from presentation (OR 0.41; 95% CI 0.27–0.61; 16 studies included). Patient delay (time from onset of symptoms to presentation or surgery) did not significantly affect the mortality in this study. None of the time-related variables assessed significantly reduced the amputation rate. Three studies reported on the duration of the first surgery. They reported a mean operating time of 78, 81, and 102 min with associated mortality rates of 4, 11.4, and 60%, respectively. Conclusion Average mortality rates reported remained constant (around 20%) over the past 20 years. Early surgical debridement lowers the mortality rate for NSTI with almost 50%. Thus, a sense of urgency is essential in the treatment of NSTI.


F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 64
Author(s):  
Shinta Oktya Wardhani ◽  
Jonny Karunia Fajar ◽  
Laksmi Wulandari ◽  
Gatot Soegiarto ◽  
Yeni Purnamasari ◽  
...  

Background: Convalescent plasma (CCP) has been used for treating some infectious diseases; however, the efficacy of CCP in coronavirus disease 2019 (COVID-19) remains controversial. The aim of this research was to assess the efficacy of CCP as an adjunctive treatment in COVID-19 patients. Methods: Four bibliographic databases and a preprint database were searched for potentially relevant articles. Mortality rates between patients treated with standard treatment and standard treatment with CCP were compared using a Z test. Results: A total of 1,937 patients treated with CCP and 3,405 patients without CCP retrieved from 12 studies were included. The risk of mortality was 1.92-fold higher in patients without CCP compared to patients treated with CCP (OR: 1.92; 95%CI: 1.33, 2.77; p=0.0005). In severe COVID-19 sub-group analysis, we found that patients without the CCP had a 1.32 times higher risk of mortality than those treated with the CCP (OR: 1.32; 95%CI: 1.09, 1.60; p=0.0040). Conclusions: CCP, as adjunctive therapy, reduces the mortality rate among COVID-19 patients.


F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 34
Author(s):  
Syahrul Syahrul ◽  
Helnida Anggun Maliga ◽  
Muhammad Ilmawan ◽  
Marhami Fahriani ◽  
Sukamto S. Mamada ◽  
...  

Background: In this study, we aimed to determine the global prevalence, chronological order of symptom appearance, and mortality rates with regard to hemorrhagic and ischemic stroke in patients with coronavirus disease 2019 (COVID-19) and to discuss possible pathogeneses of hemorrhagic and ischemic stroke in individuals with the disease. Methods: We searched the PubMed, Scopus, and Web of Science databases for relevant articles published up to November 8, 2020. Data regarding study characteristics, hemorrhagic stroke, ischemic stroke, and COVID-19 were retrieved in accordance with the PRISMA guidelines. The Newcastle-Ottawa scale was used to assess the quality of the eligible studies. The pooled prevalence and mortality rate of hemorrhagic and ischemic stroke were calculated. Results: The pooled estimate of prevalence of hemorrhagic stroke was 0.46% (95% CI 0.40%–0.53%; I2=89.81%) among 67,155 COVID-19 patients and that of ischemic stroke was 1.11% (95% CI 1.03%–1.22%; I2=94.07%) among 58,104 COVID-19 patients. Ischemic stroke was more predominant (incidence: 71.58%) than hemorrhagic stroke (incidence: 28.42%) in COVID-19 patients who experienced a stroke. In COVID-19 patients who experienced a stroke, hospital admission with respiratory symptoms was more commonly reported than that with neurological symptoms (20.83% for hemorrhagic stroke and 5.51% for ischemic stroke versus 6.94% for hemorrhagic stroke and 5.33% for ischemic stroke, respectively). The pooled mortality rate of COVID-19 patients who experienced a hemorrhagic and ischemic stroke was 44.72% (95% CI 36.73%–52.98%) and 36.23% (95% CI 30.63%–42.24%), respectively. Conclusions: Although the occurrence of hemorrhagic and ischemic stroke is low, the mortality rates of both stroke types in patients with COVID-19 are concerning, and therefore, despite several potential pathogeneses that have been proposed, studies aimed at definitively elucidating the mechanisms of hemorrhagic and ischemic stroke in individuals with COVID-19 are warranted. PROSPERO registration: CRD42020224470 (04/12/20)


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