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1.
Cristina De la Calle Olga Rodríguez Laura Morata Francesc Marco Celia Cardozo Carolina García-Vidal Ana Del Río Csaba Feher Martina Pellicé Pedro Puerta-Alcalde Josep Mensa Alex Soriano Jose Antonio Martínez 《International journal of antimicrobial agents》2019,53(4):520-524
Background
Ceftazidime-avibactam has in vitro activity against Gram-negative bacilli that produce Class A, C and some D β-lactamases, and has been successfully used in the treatment of infections caused by cephalosporin and carbapenem-resistant Enterobacteriaceae. However, actual experience in the treatment of OXA-48 carbapenemase-producing Enterobacteriaceae (CPE) is limited.Objective
To review the characteristics and prognosis of OXA-48 CPE infections treated with ceftazidime-avibactam since introduction of the drug to the current centre during the period October 2014 to December 2016.Methods
Retrospective assessment of episodes of infection caused by OXA-48 CPE treated with ceftazidime-avibactam, analysing data collected from infection diagnosis until 90 days after the end of treatment.Results
Twenty-four episodes were analysed. Ceftazidime-avibactam was given as the initial definitive treatment in 15 (62.5%) and as salvage therapy in nine (37.5%). Intraabdominal (seven, 29%), urinary (six, 25%) and respiratory (five, 21%) were the most common sources. The 30-day and 90-day mortality rates were 8.3% and 20.8%, respectively. Clinical cure at 30 days was achieved in 62.5% of episodes. Four (16.7%) patients had adverse events, two of them were related to impaired renal function. Among patients who finished the treatment with ceftazidime-avibactam, seven (35%) were diagnosed with infection recurrence within 90 days of the end of treatment.Conclusions
From experience, ceftazidime-avibactam is an effective drug for treating infections due to OXA-48 CPE. From these results a better safety profile than the current best available therapy could be expected. 相似文献2.
Benjamin Davido Rui Batista Aurélien Dinh Pierre de Truchis E.M. Terveer Bruce Roberts Ed J. Kuijper Silvia Caballero 《International journal of antimicrobial agents》2019,53(5):553-556
Background
Spontaneous decolonization of antibiotic-resistant bacteria (ARB) takes time: approximately 25% after 30 days for carbapenem-producing Enterobacteriaceae or extended-spectrum beta-lactamase-producing Enterobacteriaceae. Faecal microbiota transplantation (FMT) has been proposed as a new strategy to promote decolonization in order to reduce the risk of superinfection due to these ARB. This paper discusses the literature on the use of FMT for this indication, and the improvement levers available to promote its efficacy.Methods
Literature available to date concerning the use of FMT to eradicate ARB was reviewed, and the different factors that may have influenced the efficacy of decolonization were evaluated.Results
Four axes that could have played major roles in the efficacy of FMT were identified: bowel preparation before FMT; donor; dose; and thermal conditioning of faeces. The positive or negative impact of each on the outcome of FMT is discussed.Conclusion
Although FMT is very efficient for the eradication of Clostridium difficile, the same ‘recipe’ cannot be used for the eradication of ARB. Working together with expert centres may help to improve the efficacy of FMT for this indication, and enable the reduction of in-hospital isolation precautions. 相似文献3.
Hui Qi Chen Kou Yu-Jie Qi Bo-Hao Tang Yue-E Wu Fei Jin Xiao-Jing Luo Yan-Hua Shen Ya-Jie Guo Xue Qi Ya-Cui Wang Qian Dong Xing-Kai Chen Hai-Yan Shi Yi Zheng Wei Zhao A-Dong Shen 《International journal of antimicrobial agents》2019,53(3):347-351
Objectives
There has been recent renewed interest in historical antibiotics because of the increased antibiotic-resistant bacterial strains. Latamoxef, a semi-synthetic oxacephem antibiotic developed in 1980s, has recently been brought back into use for treatment of infections in newborns; however, it is still used off-label in neonatal clinical practice due to the lack of an evidence-based dosing regimen. This study was performed to evaluate the pharmacokinetics of latamoxef in neonates and young infants, and to provide an evidence-based dosing regimen for newborns based on developmental pharmacokinetics-pharmacodynamics (PK-PD).Methods
Opportunistic blood samples from newborns treated with latamoxef were collected to determine the latamoxef concentration by high-performance liquid chromatography with UV detection. Population PK-PD analysis was conducted using NONMEM and R software. A total of 165 plasma samples from 128 newborns (postmenstrual age range 28.4–46.1 weeks) were available for analysis.Results
A two-compartment model with first-order elimination showed the best fit with the data. Current body weight, birth weight, and postnatal age were identified as significant covariates influencing latamoxef clearance. Simulation indicated that the current dosing regimen (30 mg/kg q12h) is adequate with an MIC of 1 mg/L. For an MIC of 4 mg/L, 30 mg/kg q8h was required to achieve a target rate of 70% of patients having a free antimicrobial drug concentration exceeding the MIC during 70% of the dosing interval.Conclusions
Based on the developmental PK-PD analysis of latamoxef, a rational dosing regimen of 30 mg/kg q12h or q8h was required in newborns, depending on the pathogen. 相似文献4.
R.J. van de Peppel M.T. van der Beek L.G. Visser M.G.J. de Boer J. Wallinga 《International journal of antimicrobial agents》2019,53(3):284-293
Objectives
Triazole resistance in Aspergillus spp. is emerging and complicates prophylaxis and treatment of invasive aspergillosis (IA) worldwide. New polymerase chain reaction (PCR) tests on broncho-alveolar lavage (BAL) fluid allow for detection of triazole resistance at a genetic level, which has opened up new possibilities for targeted therapy. In the absence of clinical trials, a modelling study delivers estimates of the added value of resistance detection with PCR, and which empiric therapy would be optimal when local resistance rates are known.Design
A decision-analytic modelling study was performed based on epidemiological data of IA, extended with estimated dynamics of resistance rates and treatment effectiveness. Six clinical strategies were compared that differ in use of PCR diagnostics (used vs not used) and in empiric therapeutic choice in case of unknown triazole susceptibility: voriconazole, liposomal amphotericin B (LAmB) or both. Outcome measures were proportion of correct treatment, survival and serious adverse events.Results
Implementing aspergillus PCR tests was projected to result in residual treatment-susceptibility mismatches of <5% for a triazole resistance rate up to 20% (using voriconazole). Empiric LAmB outperformed voriconazole at resistance rates >5–20%, depending on PCR use and estimated survival benefits of voriconazole over LAmB. Combination therapy of voriconazole and LAmB performed best at all resistance rates, but the advantage over the other strategies should be weighed against the expected increased number of drug-related serious adverse events. The advantage of combination therapy over LAmB monotherapy became smaller at higher triazole resistance rates.Conclusions
Introduction of current aspergillus PCR tests on BAL fluid is an effective way to increase the proportion of patients that receive targeted therapy for IA. The results indicate that close monitoring of background resistance rates and adverse drug events are important to attain the potential benefits of LAmB. The choice of strategy ultimately depends on the probability of triazole resistance, the availability of PCR and individual patient characteristics. 相似文献5.
Anaïs Potron Maxime Bour Pauline Triponney Joris Muller Christelle Koebel Rémy A. Bonnin Patrick Plésiat 《International journal of antimicrobial agents》2019,53(5):669-673
Objectives
This study reported a hospital outbreak due to an extensively drug-resistant (XDR) OXA-72-producing strain of Acinetobacter baumannii (A. baumannii).Methods and Results
The isolates were found to be genotypically indistinguishable by whole-genome multiple locus sequence typing, and to belong to the international clonal complex CC2. One of these isolates sequentially developed a high resistance to colistin and rifampicin under treatment, as a result of mutations in genes pmrB and rpoB, respectively. The blaOXA-72 gene was localised on a 10-kb transferable plasmid, named pAB-STR-1, whose sequence is nearly identical to that of another plasmid previously found in Lithuanian strains, pAB120.Conclusion
This report highlighted the need to carefully monitor the emergence of colistin and rifampicin resistance in patients treated for infections with multidrug-resistant A. baumannii. 相似文献6.
Eve Todesco Nesrine Day Corinne Amiel Stéphane Elaerts Véronique Schneider Laurent Roudière Stéphane Hué Jean-Yves Liotier Julie Bottero Thomas L&#x;Yavanc Michel Ohayon Daniel Gosset Vincent Thibault Laure Surgers Julie Chas Sepideh Akhavan Annie Velter Christine Katlama Marc-Antoine Valantin 《International journal of antimicrobial agents》2019,53(5):678-681
Background
Increasing incidence of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-positive men having sex with men (MSM) has been described in recent years. Phylogenetic analyses of acute HCV infections were undertaken to characterize the dynamics during the epidemic in Paris, and associated sexually transmitted infections (STIs) were evaluated.Methods
Sanger sequencing of polymerase gene was performed. Maximum likelihood phylogenies were reconstructed using FastTree 2.1 under a GTR+CAT model. Transmission chains were defined as clades with a branch probability ≥0.80 and intraclade genetic distances <0.02 nucleotide substitutions per sites. STIs detected ≤1 month before HCV diagnosis were considered.Results
Among the 85 studied patients, at least 81.2% were MSM. Respectively, 47.6%, 39.0%, 11.0% and 2.4% were infected with genotypes 1a, 4d, 3a and 2k. At least 91.8% were co-infected with HIV. HCV re-infection was evidenced for 24.7% of patients and STIs for 20.0% of patients. Twenty-two transmission chains were identified, including 52 acute hepatitis C (11 pairs and 11 clusters from three to seven patients).Conclusions
These results revealed strong clustering of acute HCV infections. Thus, rapid treatment of both chronic and acute infections is needed among this population to decrease the prevalence of HCV, in combination with preventive behavioural interventions. 相似文献7.
Xuelian Zhang Yan Li Weiwei Wang Jing Zhang Yuan Lin Bin Hong Xuefu You Danqing Song Yanchang Wang Jiandong Jiang Shuyi Si 《International journal of antimicrobial agents》2019,53(4):442-448
Introduction
The emergence of drug-resistant Gram-negative bacteria is a serious clinical problem that causes increased morbidity and mortality. However, the slow discovery of new antibiotics is unable to meet the need for treating bacterial infections caused by drug-resistant strains. Lipopolysaccharide (LPS) is synthesized in the cytoplasm and transported to the cell envelope by the LPS transport (Lpt) system. LptA and LptC form a complex that transports LPS from the inner membrane to the outer membrane.Methods
This study performed a screen for agents that disrupt the transport of LPS in Gram-negative bacteria Escherichia coli. It established a yeast two-hybrid system to detect LptA-LptC interaction and used this system to identify a compound, IMB-881, that blocks this interaction and shows antibacterial activity.Results
This study demonstrated that the IMB-881 compound specifically binds to LptA to disrupt LptA-LptC interaction using surface plasmon resonance assay. Overproduction of LptA protein but not that of LptC lowered the antibacterial activity of IMB-881. Strikingly, Escherichia coli cells accumulated ‘extra’ membrane material in the periplasm and exhibited filament morphology after treatment with IMB-881.Conclusion
This study successfully identified, by using a yeast two-hybrid system, an antibacterial agent that likely blocks LPS transport in Gram-negative bacteria. 相似文献8.
Aaron J. Heffernan Fekade B. Sime Jeffrey Lipman Jayesh Dhanani Katherine Andrews David Ellwood Keith Grimwood Jason A. Roberts 《International journal of antimicrobial agents》2019,53(3):234-245
Background
Knowledge of antibiotic concentrations achievable in the epithelial lining fluid (ELF) will help guide antibiotic dosing for treating patients with Gram-negative bacillary ventilator-associated pneumonia (VAP).Objective
To compare: (1) the ELF:serum penetration ratio of antibiotics in patients with pneumonia, including VAP, with that in healthy study participants; and (2) the ELF and/or tracheal aspirate antibiotic concentrations following intravenous and nebuliser delivery.Methods
Web of Science, EMBASE and PubMed databases were searched and a systematic review undertaken.Results
Fifty-two studies were identified. ELF penetration ratios for aminoglycosides and most β-lactam antibiotics administered intravenously were between 0.12 and 0.57, whereas intravenous colistin may be undetectable in the ELF. In contrast, estimated mean fluoroquinolone ELF penetration ratios of up to 1.31 were achieved. Importantly, ELF penetration ratios appear reduced in critically ill patients with pneumonia compared with in healthy volunteers receiving intravenous ceftazidime, levofloxacin and fosfomycin; thus, dose adjustment is likely to be required in critically ill patients. In contrast to the systemic administration route, nebulisation of antibiotics achieves high ELF concentrations. Nebulised 400 mg twice-daily amikacin resulted in a median peak ELF steady-state concentration of 976.01 mg/L (interquartile range 410.3–2563.1 mg/L). Similarly, nebulised 1 million international units of colistin resulted in a peak ELF concentration of 6.73 mg/L (interquartile range 4.80–10.10 mg/L).Conclusion
Further pharmacokinetic studies investigating the mechanisms for ELF penetration in infected patients and healthy controls are needed to guide antibiotic dosing in VAP and to determine the potential benefits of nebulised therapy. 相似文献9.
Nadia Saïdani Jean-Christophe Lagier Nadim Cassir Matthieu Million Sophie Baron Grégory Dubourg Carole Eldin Jad Kerbaj Camille Valles Didier Raoult Philippe Brouqui 《International journal of antimicrobial agents》2019,53(4):355-361
Background
Colonisation with carbapenemase-producing Enterobacteriaceae or Acinetobacter (CPE/A) is associated with complex medical care requiring implementation of specific isolation policies and limitation of patient discharge to other medical facilities. Faecal microbiota transplantation (FMT) has been proposed in order to reduce the duration of gut colonisation.Objectives
This study investigated whether a dedicated protocol of FMT could reduce the negativation time of CPE/A intestinal carriage in patients whose medical care has been delayed due to such colonisation.Method
A matched case-control retrospective study between patients who received FMT treatment and those who did not among CPE/A-colonised patients addressed for initial clustering at the current institute. The study adjusted two controls per case based on sex, age, bacterial species, and carbapenemase type. The primary outcome was delay in negativation of rectal-swab cultures.Results
At day 14 post FMT, 8/10 (80%) treated patients were cleared for intestinal CPE/A carriage. In the control group, 2/20 (10%) had spontaneous clearance at day 14 after CPE/A diagnosis. Faecal microbiota transplantation led patients to reduce the delay in decolonisation (median 3 days post FMT for treated patients vs. 50.5 days after the first documentation of digestive carriage for control patients) and discharge from hospital (median 19.5 days post FMT for treated patients vs. 41 for control patients).Conclusion
Faecal microbiota transplantation is a safe and time-saving procedure to discharge CPE/A-colonised patients from the hospital. A standardised protocol, including 5 days of antibiotic treatment, bowel cleansing and systematic indwelling devices removal, should improve protocol effectiveness. 相似文献10.
T.G. Ribeiro Â. Novais C. Rodrigues R. Nascimento F. Freitas E. Machado L. Peixe 《International journal of antimicrobial agents》2019,53(5):650-656
Objectives
The objective of this work was to provide detailed molecular data on clinically acquired AmpC (qAmpC)-producing Enterobacteriaceae from two different periods (2002–2008 and 2010–2013) in order to clarify the contribution of clonal and plasmid genetic platforms for the current epidemiological scenario concerning extended-spectrum beta-lactams resistance.Methods
We analysed 1246 Enterobacteriaceae non-susceptible to third-generation cephalosporins from two hospitals and one community laboratory between 2010 and 2013. Bacterial identification, antibiotic susceptibility, identification of qAmpC and plasmid-mediated quinolone resistance genes, clonal (pulsed-field gel electrophoresis (PFGE), Multilocus sequence typing (MLST)) and plasmid (S1-/I-CeuI-PFGE, replicon typing, hybridization) analysis were performed by standard methods. Whole-genome sequencing (WGS) was performed in two ST11-Klebsiella pneumoniae isolates harbouring DHA-1.Results
The occurrence of qAmpC was lower (2.6%) than that observed in a previous survey (7.4%), and varied slightly over time. Isolates produced DHA-1 (53%), CMY-2 (44%) or DHA-6 (3%), but significant epidemiological changes were observed in the two surveys. While DHA-1 persisted in different institutions by selection of a worldwide epidemic IncR plasmid in an ST11 harbouring KL105, CMY-2 rates increased over time linked to IncI1 plasmids (instead of IncK or IncA/C2) in multiple Escherichia coli clones.Conclusions
The higher frequency of DHA-1 qAmpC in these species contrasts with the scenario in most European countries. Furthermore, the different genetic backgrounds associated with either extended-spectrum β-lactamases (ESBLs) or acquired AmpC β-lactamases (qAmpC) in our country might have contributed to their differential expansion. 相似文献11.
Shawn T. Clark Utkarshna Sinha Yu Zhang Pauline W. Wang Sylva L. Donaldson Bryan Coburn Valerie J. Waters Yvonne C.W. Yau D. Elizabeth Tullis David S. Guttman David M. Hwang 《International journal of antimicrobial agents》2019,53(5):620-628
Objective
Determining the mechanisms that modulate β-lactam resistance in clinical Pseudomonas aeruginosa (P. aeruginosa) isolates can be challenging, as the molecular profiles identified in mutation-based or expression-based resistance determinant screens may not correlate with in vitro phenotypes. One of the lesser studied resistance mechanisms in P. aeruginosa is the modification of penicillin-binding protein 3 (pbpB/ftsI). This study reported that nonsynonymous polymorphisms within pbpB frequently occur among β-lactam resistant sputum isolates, and are associated with unique antibiotic susceptibility patterns.Methods
Longitudinally collected isolates (n?=?126) from cystic fibrosis (CF) patients with or without recent β-lactam therapy or of non-clinical origin were tested for susceptibility to six β-lactams (aztreonam, ceftazidime, cefsulodin, cefepime, meropenem, and piperacillin). Known β-lactam resistance mechanisms were characterised by polymerase chain reaction (PCR)-based methods, and polymorphisms in the transpeptidase-encoding domain of pbpB identified by sequencing.Results
Twelve nonsynonymous polymorphisms were detected among 86 isolates (67%) from five CF patients with a history of β-lactam therapy, compared with one polymorphism in 30 (3.3%) from three patients who had not received β-lactam treatments. No nonsynonymous polymorphisms were found in ten environmental isolates. Multiple pbpB alleles, often with different combinations of polymorphisms, were detected within the population of strains from each CF patient for up to 2.6 years. Traditional patterns of ampC or mexA de-repression reduced expression of oprD or the presence of extended-spectrum β-lactamases were not observed in resistant isolates with nonsynonymous polymorphisms in pbpB.Conclusion
This study's findings suggest that pbpB is a common adaptive target, and may contribute to the development of β-lactam resistance in P. aeruginosa. 相似文献12.
Christopher J. Destache David J. Guervil Keith S. Kaye 《International journal of antimicrobial agents》2019,53(5):644-649
Background
The clinical experience of ceftaroline fosamil (CPT-F) therapy for Gram-positive infective endocarditis is reported from CAPTURE, a retrospective study conducted in the USA.Methods
Data, including patient demographics, medical history, risk factors, microbiological aetiology and clinical outcomes, were collected by review of patient charts between September 2013 and February 2015.Results
Patients (n=55) with Gram-positive endocarditis were treated with CPT-F. The most common risk factors were intravascular devices (43.6%), diabetes mellitus (40.0%) and injection drug use (38.2%). The most commonly isolated pathogens were meticillin-resistant Staphylococcus aureus (MRSA; 80%), meticillin-susceptible S. aureus (MSSA; 7.3%) and coagulase-negative staphylococci (7.3%). CPT-F was given as first-line therapy in 7.3% of patients and as second-line or later therapy in 92.7% of patients, and as monotherapy in 41.8% of patients and as concurrent therapy in 58.2% of patients. Clinical success was observed in 82.6% (19/23) of patients treated with CPT-F as monotherapy. In patients treated with CPT-F as first-line therapy or second-line or later therapy, 75.0% (3/4) and 70.6% (36/51) achieved success, respectively. Clinical success was observed in 77.3% (34/44) of patients with MRSA and 25% (1/4) of patients with MSSA. Two patients discontinued treatment with CPT-F due to an adverse event.Conclusions
CPT-F treatment was associated with a high rate of clinical success in patients with Gram-positive infective endocarditis, including those with risk factors and infections caused by MRSA. A high rate of clinical success was observed in patients treated with CPT-F used as first- line therapy or second-line or later therapy, or as monotherapy or in combination with other antibiotics. 相似文献13.
Charles-Edouard Luyt Morgane Faure Isabelle Bonnet Sébastien Besset Florent Huang Helga Junot Guillaume Hékimian Matthieu Schmidt Nicolas Bréchot Alain Combes Alexandra Aubry Julien Mayaux Jean Chastre 《International journal of antimicrobial agents》2019,53(5):547-552
Objectives
The aim of this study was to evaluate the use of non-carbapenem antibiotics to treat severe extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) infections in intensive care unit (ICU) patients.Methods
This retrospective observational study conducted in two ICUs compared the outcomes of patients with ESBL-E infections administered a carbapenem or a non-carbapenem antibiotic as their definitive treatment. The primary outcome was treatment failure within 30 days, a composite endpoint of ESBL-E infection recurrence and 30-day mortality. Secondary outcomes included 30-day and in-hospital mortality rates, ESBL-E infection recurrence and infection(s) due to other pathogen(s).Results
Among 107 patients included in the study, 67 received a carbapenem and 40 received a non-carbapenem antibiotic as their definitive treatment. Clinical characteristics of the two groups were similar. Comparing patients given a non-carbapenem antibiotic with those administered a carbapenem, they had similar 30-day treatment failure (43% vs. 61%, respectively; P?=?0.06) and ESBL-E infection recurrence rates (25% vs. 22%; P?=?0.8), but the former had lower 30-day mortality (23% vs. 45%; P?=?0.02) and in-hospital mortality rates (23% vs. 49%; P?=?0.005). Secondary infection rates caused by other pathogen(s), including Clostridium difficile, were comparable. Outcomes were comparable regardless of whether or not patients received an empirical carbapenem.Conclusion
For ICU patients with severe ESBL-E infections, treatment with a non-carbapenem antibiotic was not associated with poorer outcomes compared with a carbapenem antibiotic. 相似文献14.
Joan Gómez-Junyent Eva Benavent Yanik Sierra Cristina El Haj Laura Soldevila Benjamín Torrejón Raul Rigo-Bonnin Fe Tubau Javier Ariza Oscar Murillo 《International journal of antimicrobial agents》2019,53(5):612-619
Objectives
Ceftolozane/tazobactam is a potential tool for infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa), but its efficacy against some difficult-to-treat infections has not been well defined.Methods
Using an in vitro pharmacodynamic biofilm model, this study evaluated the comparative efficacy of ceftolozane/tazobactam against MDR/extensively drug-resistant (XDR) P. aeruginosa strains, alone and in combination with colistin. Simulated regimens of ceftolozane/tazobactam (2 g/1 g every 8 h), meropenem (2 g every 8 h) and ceftazidime (2 g every 8 h), alone and in combination with colistin (continuous infusion) were evaluated against three colistin-susceptible and ceftazidime-resistant strains: MDR-HUB1, ceftolozane/tazobactam-susceptible and meropenem-susceptible; XDR-HUB2, ceftolozane/tazobactam-susceptible and meropenem-resistant; MDR-HUB3, ceftolozane/tazobactam-resistant and meropenem-susceptible. Antibiotic efficacy was evaluated by decreases in bacterial counts (Δlog CFU/mL) from biofilm-embedded bacteria over 54 h. Resistance emergence was screened.Results
Among monotherapies, ceftolozane/tazobactam had low killing but no resistance appeared, ceftazidime was ineffective, colistin was initially effective but regrowth and resistance occurred, and meropenem was bactericidal against carbapenem-susceptible strains. Ceftolozane/tazobactam plus colistin was the most effective combination against the meropenem-resistant XDR-HUB2 strain (Δlog CFU/mL 54–0 h?=?–4.42 vs. –3.54 for meropenem-colistin; P?=?0.002), whereas this combination against MDR-HUB1 (–4.36) was less effective than meropenem-colistin (–6.25; P < 0.001). Ceftolozane/tazobactam plus colistin was ineffective against the ceftolozane/tazobactam-resistant strain; meropenem plus colistin was the most bactericidal therapy (–6.37; P < 0.001 vs. others). Combinations of active beta-lactams plus colistin prevented the emergence of colistin-resistant strains.Conclusions
Combinations of colistin plus ceftolozane/tazobactam and meropenem were the most appropriate treatments for biofilm-related infections caused by XDR and MDR P. aeruginosa strains, respectively. These combinations could be considered as potential treatment options for these difficult to treat infections. 相似文献15.
Li Wen Loo Yi Xin Liew Winnie Lee Lai Wei Lee Piotr Chlebicki Andrea Lay-Hoon Kwa 《International journal of antimicrobial agents》2019,53(5):606-611
Background
Overprescribing antibiotics for patients with no bacterial infection is of growing global concern. It is important for timely Antimicrobial Stewardship Program (ASP) intervention to discontinue antibiotics for patients whose symptoms can be explained by non-infective causes, and without availability of bacterial cultures and susceptibilities reports. This study aimed to evaluate clinical outcomes and safety of early ASP review in these patients.Methods
A retrospective review of the ASP database (January 2010 to December 2014) was conducted to identify patients for whom ASP recommended discontinuation of empiric antibiotics within 24 hours of prescribing. Demographics were collected. Clinical outcomes – duration of therapy, length of hospital stay (LOS), infection-related readmissions, and all-cause mortality – were compared between interventions accepted and rejected groups. Continuous data were analysed via unpaired Student's t-test. Categorical data were analysed using χ2 test or Fisher's exact test, as appropriate.Results
The ASP team recommended 794 interventions (overall acceptance rate of 72.9%, 579 of 794). There were no significant between-group differences in underlying demographics, and Charlson comorbidity index score. However, the interventions acceptance group had significantly shorter duration of therapy by 2.61 days (2.72 ± 3.04 vs. 5.33 ± 2.54 days; P < 0.01) and LOS by 7.41 days (7.98 ± 13.14 vs. 15.39 ± 22.62 days; P < 0.01), with estimated cost savings of SGD10 817 per patient. There were no significant between-group differences in 14-day mortality and readmission rates.Conclusion
Prompt ASP interventions at Singapore General Hospital were associated with significant reductions in duration of therapy and LOS, with cost savings. It was demonstrated that it is safe to discontinue antibiotics within 24 hours of prescribing for patients with no evidence of bacterial infections. 相似文献16.
Sarah Wilkes Inge van Berlo Jaap ten Oever Frank Jansman Rob ter Heine 《International journal of antimicrobial agents》2019,53(3):310-317
Objective
This study's objective was to describe the population pharmacokinetics of total and unbound flucloxacillin in non-critically ill patients, and to devise a rational continuous dosing regimen for this population.Methods
Total and unbound flucloxacillin pharmacokinetics in 30 non-critically ill patients receiving intravenous flucloxacillin were analysed using non-linear mixed-effects modelling. Monte Carlo simulation was used to assess the fraction of the population reaching effective unbound flucloxacillin levels and the fraction reaching potential neurotoxic exposure for various continuous dosing regimens.Results
The observed protein binding varied between 64.6–97.1%. The unbound fraction was significantly associated with serum albumin and was concentration-dependent. The parameter estimates of the final model were: Cltotal 122 L/h, Clrenal 1.41 L/h, Vc 190 L, Vp 33.9 L, Q 16.8 L/h, Kd 9.63 mg/L, θBmax 177 mg/L,θalb 0.054. A continuous dose of 6 g/24 hours was sufficient for 100% of the population to obtain a unbound concentration of > 0.25 mg/L. With 14 g/24 h, 91.2% of the population was predicted to reach concentrations of > 2 mg/L, the clinical breakpoint for Staphylococcus aureus. Potential toxic unbound flucloxacillin levels were reached in 2.0% of the population with 6 g/24 h, and 24.1% with 14 g/24 h.Conclusions
This study showed that a continuous infusion of 6 g/24 h flucloxacillin is sufficient to treat most infections in non-critically ill patients. With this dosing regimen, an unbound serum concentration flucloxacillin > 0.25 mg/L was reached in 100% of the patients, with minimal chance of neurotoxicity. 相似文献17.
Bram J. Mertens Henk-Frans Kwint Rob J. van Marum Marcel L. Bouvy 《Research in social & administrative pharmacy》2019,15(3):303-309
Background
Multidose drug dispensing (MDD) is used to help patients take their medicines appropriately. Little is known about drug regimen changes within these MDD systems and how they are effectuated by the community pharmacist. Manual immediate adjustments of the MDD system could introduce dispensing errors. MDD guidelines therefore recommend to effectuate drug regimen changes at the start of a new MDD system.Objective
The aim of this study was to investigate the frequency, type, procedure followed, immediate necessity, and time taken to make MDD adjustments.Methods
This was a cross-sectional study in eight community pharmacies in the Netherlands. All adjustments to MDD systems were systematically documented for 3 weeks by the community pharmacist.Results
Overall, 261 MDD adjustments involving 364 drug changes were documented for 250 patients: 127 (35%) drug changes involved the addition of a new drug, 124 (34%) a change in dosage, and 95 (26%) drug discontinuation. Of the MDD adjustments, 135 (52%) were effectuated immediately: 81 (31%) by adjusting the MDD system manually, 49 (19%) by temporarily dispensing the drug separately from the MDD system, and 5 (2%) by ordering a new MDD system. Pharmacists considered that 36 (27%) of the immediate MDD adjustments could have been deferred until the next MDD system was produced. Immediate adjustment took significantly longer than deferred adjustment (p?<?0.001).Conclusions
This study shows that in patients using MDD systems, over half of the drug regimen changes are adjusted immediately. The necessity of these immediate changes should be critically evaluated. 相似文献18.
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Parham Jabbarzadeh Kaboli Melody Pui-Yee Leong Patimah Ismail King-Hwa Ling 《Pharmacological reports : PR》2019,71(1):13-23