scholarly journals Beta-Lactam/Beta-Lactamase Inhibitor Therapy for Potential AmpC-Producing Organisms: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 6 (7) ◽  
Author(s):  
Matthew P Cheng ◽  
Robyn S Lee ◽  
Alexandre P Cheng ◽  
Samuel De L’étoile-Morel ◽  
Koray Demir ◽  
...  

Abstract The optimal treatment for potential AmpC-producing Enterobacteriaceae, including Serratia, Providencia, Citrobacter, Enterobacter, and Morganella species, remains unknown. An updated systematic review and meta-analysis of studies comparing beta-lactam/beta-lactamase inhibitors with carbapenems in the treatment of bloodstream infections with these pathogens found no significant difference in 30-day mortality (OR, 1.13; 95% CI, 0.58 – 2.20).

2007 ◽  
Vol 52 (2) ◽  
pp. 465-469 ◽  
Author(s):  
David L. Paterson ◽  
Carlene A. Muto ◽  
Magdaline Ndirangu ◽  
Peter K. Linden ◽  
Brian A. Potoski ◽  
...  

ABSTRACT In contrast to expanded-spectrum cephalosporins, beta-lactam-beta-lactamase inhibitor combinations such as piperacillin-tazobactam have rarely been associated with vancomycin-resistant Enterococcus (VRE) colonization and infection. In mice, piperacillin-tazobactam has sufficient antienterococcal activity to inhibit the establishment of colonization during treatment, but this effect has not been confirmed in human patients. We prospectively evaluated the acquisition of rectal colonization by VRE among intensive care unit patients receiving antibiotic regimens containing piperacillin-tazobactam versus those receiving cefepime, an expanded-spectrum cephalosporin with minimal antienterococcal activity. Rectal swabs were obtained weekly and were cultured for VRE. For 146 patients with a negative rectal swab for VRE prior to therapy, there was no significant difference in the frequency of VRE acquisition between patients receiving piperacillin-tazobactam- and cefepime-containing regimens (19/72 [26.4%] and 23/74 [31.1%], respectively; P = 0.28). Of the 19 patients who acquired VRE in association with piperacillin-tazobactam, 10 (53%) developed the new detection of VRE during therapy. Patients initiated on treatment with cefepime-containing regimens were significantly more likely than those initiated on treatment with piperacillin-tazobactam-containing regimens to have received antibiotic therapy in the prior 30 days (55/74 [74.3%] and 22/72 [30.6%], respectively; P < 0.001). These findings suggest that piperacillin-tazobactam- and cefepime-containing antibiotic regimens may be associated with the frequent acquisition of VRE in real-world intensive care unit settings. Although piperacillin-tazobactam inhibits the establishment of VRE colonization in mice when exposure occurs during treatment, our data suggest that this agent may not prevent the acquisition of VRE in patients.


2020 ◽  
Vol 27 (37) ◽  
pp. 6373-6383 ◽  
Author(s):  
Leila Jouybari ◽  
Faezeh Kiani ◽  
Farhad Islami ◽  
Akram Sanagoo ◽  
Fatemeh Sayehmiri ◽  
...  

: Breast cancer is the most common neoplasm, comprising 16% of all women's cancers worldwide. Research of Copper (Cu) concentrations in various body specimens have suggested an association between Cu levels and breast cancer risks. This systematic review and meta-analysis summarize the results of published studies and examine this association. We searched the databases PubMed, Scopus, Web of Science, and Google Scholar and the reference lists of relevant publications. The Standardized Mean Differences (SMDs) between Cu levels in cancer cases and controls and corresponding Confidence Intervals (CIs), as well as I2 statistics, were calculated to examine heterogeneity. Following the specimens used in the original studies, the Cu concentrations were examined in three subgroups: serum or plasma, breast tissue, and scalp hair. We identified 1711 relevant studies published from 1984 to 2017. There was no statistically significant difference between breast cancer cases and controls for Cu levels assayed in any studied specimen; the SMD (95% CI) was -0.01 (-1.06 - 1.03; P = 0.98) for blood or serum, 0.51 (-0.70 - 1.73; P = 0.41) for breast tissue, and -0.88 (-3.42 - 1.65; P = 0.50) for hair samples. However, the heterogeneity between studies was very high (P < 0.001) in all subgroups. We did not find evidence for publication bias (P = 0.91). The results of this meta-analysis do not support an association between Cu levels and breast cancer. However, due to high heterogeneity in the results of original studies, this conclusion needs to be confirmed by well-designed prospective studies.


2019 ◽  
Vol 17 (2) ◽  
pp. 191-203
Author(s):  
Oliver Brown ◽  
Jennifer Rossington ◽  
Gill Louise Buchanan ◽  
Giuseppe Patti ◽  
Angela Hoye

Background and Objectives: The majority of patients included in trials of anti-platelet therapy are male. This systematic review and meta-analysis aimed to determine whether, in addition to aspirin, P2Y12 blockade is beneficial in both women and men with acute coronary syndromes. </P><P> Methods: Electronic databases were searched and nine eligible randomised controlled studies were identified that had sex-specific clinical outcomes (n=107,126 patients). Risk Ratios (RR) and 95% Confidence Intervals (CI) were calculated for a composite of cardiovascular death, myocardial infarction or stroke (MACE), and a safety endpoint of major bleeding for each sex. Indirect comparison analysis was performed to statistically compare ticagrelor against prasugrel. </P><P> Results: Compared to aspirin alone, clopidogrel reduced MACE in men (RR, 0.79; 95% CI, 0.68 to 0.92; p=0.003), but was not statistically significant in women (RR, 0.88; 95% CI, 0.75 to 1.02, p=0.08). Clopidogrel therapy significantly increased bleeding in women but not men. Compared to clopidogrel, prasugrel was beneficial in men (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02) but not statistically significant in women (RR, 0.94; 95% CI, 0.83 to 1.06; p=0.30); ticagrelor reduced MACE in both men (RR, 0.85; 95% CI, 0.77 to 0.94; p=0.001) and women (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02). Indirect comparison demonstrated no significant difference between ticagrelor and prasugrel in either sex. Compared to clopidogrel, ticagrelor and prasugrel increased bleeding risk in both women and men. </P><P> Conclusion: In summary, in comparison to monotherapy with aspirin, P2Y12 inhibitors reduce MACE in women and men. Ticagrelor was shown to be superior to clopidogrel in both sexes. Prasugrel showed a statistically significant benefit only in men; however indirect comparison did not demonstrate superiority of ticagrelor over prasugrel in women.


1997 ◽  
Vol 41 (4) ◽  
pp. 721-727 ◽  
Author(s):  
P D Lister ◽  
A M Prevan ◽  
C C Sanders

An in vitro pharmacokinetic model was used to study the pharmacodynamics of piperacillin-tazobactam and piperacillin-sulbactam against gram-negative bacilli producing plasmid-encoded beta-lactamases. Logarithmic-phase cultures were exposed to peak antibiotic concentrations observed in human serum after the administration of intravenous doses of 3 g of piperacillin and 0.375 g of tazobactam or 0.5 g of sulbactam. Piperacillin and inhibitor were either dosed simultaneously or piperacillin was dosed sequentially 0.5 h after dosing with the inhibitor. In studies with all four test strains, the pharmacodynamics observed after simultaneous dosing were similar to those observed with the sequential regimen. Since the ratio between piperacillin and tazobactam was in constant fluctuation after sequential dosing, these data suggest that the pharmacodynamics of the piperacillin-inhibitor combinations were not dependent upon maintenance of a critical ratio between the components. Furthermore, when regrowth was observed, the time at which bacterial counts began to increase was similar between the simultaneous and sequential dosing regimens. Since the pharmacokinetics of the inhibitors were the same for all regimens, these data suggest that the length of time that the antibacterial activity was maintained over the dosing interval with these combinations was dictated by the pharmacokinetics of the beta-lactamase inhibitor in the combination. The antibacterial activity of the combination appeared to be lost when the amount of inhibitor available fell below some critical concentration. This critical concentration varied depending upon the type and amount of enzyme produced, as well as the specific inhibitor used. These results indicate that the antibacterial activity of drug-inhibitor combinations, when dosed at their currently recommended ratios, is more dependent on the pharmacokinetics of the inhibitor than on those of the beta-lactam drug.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Aongart Mahittikorn ◽  
Frederick Ramirez Masangkay ◽  
Kwuntida Uthaisar Kotepui ◽  
Giovanni De Jesus Milanez ◽  
Manas Kotepui

Abstract Background Malaria mixed infections are often unrecognized by microscopists in the hospitals, and a delay or failure to treat Plasmodium-mixed infection may lead to aggravated morbidity and increased mortality. The present study aimed to quantify the pooled proportion and risk of malarial recurrences after the treatment of Plasmodium-mixed infection. The results of the study may provide benefits in the management of Plasmodium-mixed infection in co-endemic regions. Methods This systematic review and meta-analysis searched the international Prospective Register of Systematic Reviews (PROSPERO; ID = CRD42020199709), MEDLINE, Web of Science, and Scopus for potentially relevant studies in any language published between January 1, 1936, and July 20, 2020, assessing drug efficacy in patients with Plasmodium-mixed infection. The primary outcome was the pooled prevalence of Plasmodium parasitemia after initiating antimalarial treatment for Plasmodium-mixed infection. The secondary outcome was the pooled risk ratio (RR) of malarial recurrence in Plasmodium-mixed infection compared with those in Plasmodium falciparum and Plasmodium vivax mono-infection. The pooled analyses were calculated by random-effects meta-analysis. After the initial treatment in different days of recurrences (≤ 28 days or > 28 days), the risk of Plasmodium parasitemia was compared in subgroup analysis. Results Out of 5217 screened studies, 11 were included in the meta-analysis, including 4390 patients from six countries. The pooled prevalence of all recurrences of Plasmodium-mixed parasitemia was 30% (95% confidence interval (CI) 16–43; I2: 99.2%; 11 studies). The RR of malarial recurrence within 28 days after the initial treatment (clinical treatment failure) of Plasmodium-mixed parasitemia compared with the treatment of P. falciparum was 1.22 (p: 0.029; 95% CI 1.02–1.47; Cochran Q: 0.93; I2: 0%; six studies), while there was no significant difference in the risk of recurrence 28 days after initial treatment compared with the treatment of P. falciparum (p: 0.696, RR: 1.14; 95% CI 0.59–2.18; Cochran Q < 0.05; I2: 98.2%; four studies). The subgroup analysis of antimalarial drugs showed that significant malarial recurrence within 28 days was observed in patients treated with artemisinin-based combination therapies (ACTs) with no significant heterogeneity (p: 0.028, RR: 1.31; 95% CI 1.03–1.66; Cochran Q: 0.834; I2: 0%). Conclusions The present findings showed a high prevalence of malarial recurrence after the initial treatment of Plasmodium-mixed infection. Moreover, significant malaria recurrence of mixed infection occurred within 28 days after treatment with ACTs. Graphic Abstract


2021 ◽  
Author(s):  
Fardowsa Mohamed ◽  
Megna Jeram ◽  
Christin Coomarasamy ◽  
Melanie Lauti ◽  
Don Wilson ◽  
...  

Abstract Introduction Obesity increases the risk of pelvic floor disorders in individuals with obesity, including faecal incontinence. Faecal incontinence (FI) is a condition with important clinical and psychosocial consequences. Though it is associated with obesity, the effect of bariatric surgery on the prevalence and severity of FI is not well reported. Objective To assess the effect of bariatric surgery on the prevalence and severity of FI in adult patients with obesity. Methods This systematic review was conducted in accordance with the PRISMA statement. Two independent reviewers performed a literature search in MEDLINE, PubMed, Cochrane and Embase from 1 January 1980 to 12 January 2019. We included published English-language randomized control trials and observational studies assessing pre- and post-bariatric surgery prevalence or severity of FI. Random-effects models with DerSimonian and Laird’s variance estimator were used for meta-analysis. Results Thirteen studies were included, eight assessing prevalence (678 patients) and 11 assessing severity of FI (992 patients). There was no significant difference in prevalence post-operatively overall, though it trended towards a reduction [pooled OR=0.55; =0.075]. There was a significant reduction of FI prevalence in women post-bariatric surgery [95% CI 0.22 to 0.94, p=0.034]. There was a statistically significant reduction in FI prevalence following Roux-en-Y gastric bypass and one anastomosis gastric bypass [0.46, 95% CI 0.26 to 0.81; p=0.007]. There was no significant reduction of incontinence episodes post-operatively [pooled mean difference =−0.17, 95% CI −0.90 to 0.56; p=0.65]. Quality of life (QOL) was not significantly improved post-bariatric surgery [mean differences for the following facets of QOL: behaviour −0.35, 95% CI −0.94 to 0.24; depression 0.04, 95% CI −0.12 to 0.2; lifestyle −0.33, 95% CI −0.98 to 0.33; p values of 0.25, 0.61 and 0.33, respectively]. Discussion There was a significant reduction in FI prevalence in women and those who underwent Roux-en-Y or one anastomosis gastric bypass. Our results for FI prevalence overall, FI severity and impact on quality of life were not statistically significant. Larger studies are needed in this under-researched area to determine the true effect of bariatric surgery on FI. Graphical abstract


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