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1.
Konstantinos Z. Vardakas Andreas D. Mavroudis Maria Georgiou Matthew E. Falagas 《International journal of antimicrobial agents》2018,51(4):535-547
Background
To evaluate whether intravenous colistin in combination with other antibiotics (IVCC) is associated with lower mortality compared with intravenous colistin monotherapy (IVCM), and to identify factors influencing study outcomes.Methods
PubMed and Scopus were searched up to November 2016. Studies were included if they evaluated adult patients with multi-drug-resistant (MDR) or extensively-drug-resistant Gram-negative infections, and reported comparative mortality data (adjusted and unadjusted) for patients receiving IVCC vs. IVCM. Random effects meta-analyses were performed.Findings
Thirty-two studies (29 observational, three randomized) were included. The overall quality of data was low to very low, and studies were characterized by the lack of adjusted data. The majority of studies were not designed to evaluate the outcome of the meta-analysis, and focused mainly on infections due to Acinetobacter baumannii and Klebsiella pneumoniae. Colistin was administered at variable doses, with or without a loading dose, and in combination with several antibiotics. Overall, IVCC was not associated with lower mortality than IVCM [32 studies, 2328 patients, risk ratio (RR) 0.91, 95% confidence interval (CI) 0.81–1.02, I2 8%]. A significant difference was observed in favour of IVCC when high-dose (>6 million international units) colistin was used (RR 0.80, 95% CI 0.69–0.93), in studies conducted in Asia (RR 0.82, 95% CI 0.71–0.95), in patients with bacteraemia (RR 0.75, 95% CI 0.57–0.98) and in patients with acinetobacter infections (RR 0.88, 95% CI 0.78–1.00).Interpretation
Overall, low-quality data suggest that IVCC did not lower mortality in patients with MDR Gram-negative infections. However, there is some evidence for a benefit observed with high intravenous doses of colistin. 相似文献2.
Justin Tenney Nicholas Hudson Hazar Alnifaidy Justin Ting Cheung Li Kathy Harriet Fung 《Saudi Pharmaceutical Journal》2018,26(5):678-684
Background
This is the first review to analyze literature identifying risk factors for a multidrug-resistant urinary tract infection (MDR UTI). Risk factors for other infections involving multidrug-resistant organisms have been evaluated in other reviews, but they do not assess urinary tract infections. The purpose of this study is to collect currently published data to determine the most commonly and consistently identified risk factors for UTIs.Material and methods
For this study, 3 independent researchers searched PubMed, Embase, and Cochrane database from 1966 to February 2016 for articles identifying risk factors for MDR UTI.Results
A total of 25 studies including 31,284 patients with positive cultures provide evidence for 12 possible risk factors for MDR UTI . The most commonly identified risk factor was previous antibiotic usage as evidenced in 16 of the 20 studies that evaluated this possible risk factor. The time range utilized to define previous antibiotic usage ranged from 2?days to 365?days. Other risk factors with the strongest supporting data were urinary catheterization, previous hospitalization, and nursing home residence.Conclusion
We identified 12 different possible risk factors for a MDR UTI, however several risk factors have minimal or conflicting evidence. The definitions of the risk factors varied widely among the studies, and should be standardized for future studies. 相似文献3.
Khawla Abu Hammour Mariam Abdel Jalil Walid Abu Hammour 《Saudi Pharmaceutical Journal》2018,26(6):780-785
Objectives
The present study aimed to evaluate the parents' knowledge, attitudes and practices (KAP) towards the use of antibiotics for childhood upper respiratory tract infections (URTIs), at the Jordanian University Hospital.Methods
This was a cross-sectional study. During the study period, 1301 parents of young children completed a validated – structured questionnaire.Results
Gaps in common knowledge related to antibiotics and their use were noted among participants. Nearly half of respondents believed that antibiotics are void from adverse effects, while 72.4% of them believed that a child should be given an antibiotic if it develops fever, even though 60% they were aware that most URTIs were viral in nature. Parents reported that they administered antibiotics to children without medical advice most of the time for various causes, including using a previously prescribed antibiotic for a similar illness (27.1%), or based on pharmacist's recommendation (23.8%).Conclusion
The results demonstrated the need for educational interventions to increase the awareness of parents about antibiotics to reduce inappropriate use and its consequences. 相似文献4.
Eric Wenzler Kristen L. Bunnell Larry H. Danziger 《International journal of antimicrobial agents》2018,51(5):700-706
Background
There is a need to identify practice patterns of polymyxin use, quantify gaps in knowledge, and recognize areas of persistent confusion.Methods
A structured electronic survey was distributed to physicians, pharmacists and microbiologists. Demographic information was obtained, along with data regarding availability, stewardship principles, therapeutic usage, dosing, microbiological testing, and knowledge, attitudes and beliefs regarding the polymyxins.Results
In total, there were 420 respondents with a median of 8 (interquartile range 4–15) years of experience in infectious diseases (52.5%) and critical care (35%). Of the respondents who reported that only one polymyxin was available for use, 17.1% used polymyxin B. Over half (52.5%) of the respondents utilized a loading dose very often/always, and 66.8% dosed both polymyxins in milligrams, with the most common doses of colistin and polymyxin B being 2.5?mg/kg twice daily (60.3%) and 1.5?mg/kg twice daily (65%), respectively, for patients with normal renal function. Polymyxins were most often used for respiratory infections (63%) in combination with a carbapenem (63.6%). Approximately 85% of respondents reported their knowledge level to be fair, good or very good, although 34.9% answered two of the three knowledge questions incorrectly. More than 70% of respondents agreed that confusion exists in all surveyed areas of polymyxin use. Almost all respondents (91.2%) agreed that a polymyxin guideline would be a helpful resource.Conclusions
This survey revealed objective and subjective variability in the use and perception of the polymyxins, and identified several areas in which they were being used contrary to the available evidence. The information provided herein lays the framework to harmonize clinical practice, guide future research and shape consensus guidelines. 相似文献5.
Barbara A. Santevecchi Tiffeny T. Smith Shawn H. MacVane 《International journal of antimicrobial agents》2018,51(4):629-635
Background
Ceftazidime/avibactam is a newly approved β-lactam/β-lactamase inhibitor combination with activity against antibiotic-resistant Gram-negative organisms, including many carbapenem-resistant strains. Although this agent may offer a promising treatment option for serious infections with limited alternatives available, clinical experience with ceftazidime/avibactam in treatment of infections caused by multidrug-resistant Gram-negative organisms other than Klebsiella pneumoniae is limited.Methods
A retrospective case series was performed to evaluate patients treated with ceftazidime/avibactam for infections caused by organisms other than K. pneumoniae at our institution over a 1-year period. Patients aged at least 18 years who received at least one dose of ceftazidime/avibactam were eligible for inclusion. Clinical and microbiological data were collected, and investigators assessed adverse effects, microbiological cure, clinical success, and 30-day in-hospital mortality following completion of ceftazidime/avibactam therapy.Results
Ten patients were included. The most common index infection was pneumonia (n?=?6/13, 46%) and the most frequently isolated organism was Pseudomonas aeruginosa (n?=?8/21, 38%). Fifty percent of patients received ceftazidime/avibactam as monotherapy. Microbiological cure was achieved in 67% (n?=?6/9) of patients and 70% (n?=?7/10) of patients met criteria for clinical success. The 30-day in-hospital mortality rate was 30%. No patients experienced adverse events because of ceftazidime/avibactam therapy.Conclusions
For infections caused by antibiotic-resistant Gram-negative organisms other than K. pneumoniae, clinical and microbiological success rates for patients treated with ceftazidime/avibactam were similar to those that have been reported for K. pneumoniae. Ceftazidime/avibactam appears to be a promising treatment option for infections caused by a variety of resistant Gram-negative organisms when limited alternatives exist. 相似文献6.
Shaoning?Wang Shihui?Yu Yuwei?Lin Peizhi?Zou Guihong?Chai Heidi?H.?Yu Hasini?Wickremasinghe Nivedita?Shetty Junhong?Ling Jian?Li Qi??Zhou 《Pharmaceutical research》2018,35(10):187
Purpose
This study aims to develop liposomal formulations containing synergistic antibiotics of colistin and ciprofloxacin for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa.Methods
Colistin (Col) and ciprofloxacin (Cip) were co-encapsulated in anionic liposomes by ammonium sulfate gradient. Particle size, encapsulation efficiency, in vitro drug release and in vitro antibiotic activities were evaluated.Results
The optimized liposomal formulation has uniform sizes of approximately 100 nm, with encapsulation efficiency of 67.0% (for colistin) and 85.2% (for ciprofloxacin). Incorporation of anionic lipid (DMPG) markedly increased encapsulation efficiency of colistin (from 5.4 to 67.0%); however, the encapsulation efficiency of ciprofloxacin was independent of DMPG ratio. Incorporation of colistin significantly accelerated the release of ciprofloxacin from the DMPG anionic liposomes. In vitro release of ciprofloxacin and colistin in the bovine serum for 2 h were above 70 and 50%. The cytotoxicity study using A549 cells showed the liposomal formulation is as non-toxic as the drug solutions. Liposomal formulations of combinations had enhanced in vitro antimicrobial activities against multidrug resistant P. aeruginosa than the monotherapies.Conclusions
Liposomal formulations of two synergistic antibiotics was promising against multidrug resistant P. aeruginosa infections.7.
Marjan Wouthuyzen-Bakker Eduard Tornero Laura Morata Prashant V. Nannan Panday Paul C. Jutte Guillem Bori Greetje A. Kampinga Alex Soriano 《International journal of antimicrobial agents》2018,51(1):38-42
Objectives
The combination of a fluoroquinolone with rifampin is one of the cornerstones in the treatment of prosthetic joint infections (PJI) caused by staphylococci. Moxifloxacin is highly active against methicillin–susceptible Staphylococcus aureus (MSSA) and, therefore, is an attractive agent to use. However, several studies reported a lowering in serum moxifloxacin levels when combined with rifampin. The clinical relevance remains unclear. We determined the outcome of patients with early acute PJI caused by MSSA treated with either moxifloxacin/rifampin or levofloxacin/rifampin.Methods
Medical files of patients treated with moxifloxacin/rifampin (University Medical Centre Groningen) or levofloxacin/rifampin (Hospital Clinic Barcelona) were retrospectively reviewed (2005–2015). Treatment failure was defined as the need for revision surgery and/or suppressive therapy, death by infection or a relapse of infection during follow-up.Results
Differences in baseline characteristics between the two cohorts were observed, but prognostic parameters for failure, as defined by the KLIC-score (Kidney failure, Liver cirrhosis, Index surgery, C–reactive protein and Cemented prosthesis), were similar in the two groups (2.9 [1.5 SD] for the moxifloxacin group vs. 2.2 [1.2 SD] for the levofloxacin group [P?=?0.16]). With a mean follow-up of 50 months (36 SD) in the moxifloxacin group, and 67 months (50 SD) in the levofloxacin group (P?=?0.36), treatment was successful in 89% vs. 87.5%, respectively (P?=?0.89). None of the failures in the moxifloxacin group were due to rifampin– or moxifloxacin–resistant S. aureus strains.Conclusion
Our data indicate that moxifloxacin combined with rifampin is as clinically effective as levofloxacin/rifampin for early acute PJI caused by MSSA. 相似文献8.
Eyal Kleinhendler Matan J. Cohen Allon E. Moses Ora Paltiel Jacob Strahilevitz Amos Cahan 《International journal of antimicrobial agents》2018,51(1):71-76
Background
There are several empiric antibiotic treatment options for febrile neutropenia, yet there is no universally-accepted initial protocol. We aimed to assess the performance of a protocol (piperacillin, gentamicin and cefazolin) introduced over 40 years ago and compare its coverage against bacteria isolated from blood of neutropenic patients with that of various commonly used antibiotic treatment protocols.Methods
Adults with neutropenia admitted between 2003 and 2012 to the hemato-oncologic departments and in whom blood cultures were taken on admission were included. Appropriateness of several common antibiotic protocols was assessed based on the susceptibility of the blood isolates. Crude mortality rates were computed by the susceptibility of bacteria isolated from patients' blood to the actual treatment given.Results
In total, 180 admissions of neutropenic patients (95 in patients who had fever above 38?°C) with positive blood cultures were analyzed. The actual antibiotic regimen prescribed was deemed appropriate in 82% of bacteremia episodes. The recommended institutional protocol was used in 62% of bacteremia episodes in neutropenic patients. This protocol would have been appropriate in 85% of all neutropenic bacteremia episodes and 89% of episodes in febrile neutropenia patients compared with piperacillin/tazobactam (79%, P?=?0.13 and 76%, P?=?0.002, respectively) and imipenem (93%, P?=?0.004 and 92%, P?=?0.74, respectively). Isolation of bacteria resistant to the actual antibiotic treatment given was associated with higher mortality at one week and at 30 days.Conclusion
Common current antibiotic regimens provide similar coverage among febrile neutropenic patients, whereas broad spectrum antibiotic combinations maximize coverage among neutropenic patients. 相似文献9.
Michael A. Pfaller Robert K. Flamm Mariana Castanheira Helio S. Sader Rodrigo E. Mendes 《International journal of antimicrobial agents》2018,51(4):608-611
Background
Osteomyelitis is a difficult-to-treat infection that regularly involves prolonged use of systemic antibiotics. Dalbavancin has demonstrated activity against Gram-positive isolates, and has been considered as a candidate for the treatment of osteomyelitis in adults and children. This study evaluated the activity of dalbavancin against pathogens isolated from bone and joint infections (BJI).Methods
Eight hundred and one Staphylococcus aureus, 160 coagulase-negative staphylococci (CoNS), 164 β-haemolytic streptococci (BHS), 82 Enterococcus faecalis and 45 viridans group streptococci (VGS) causing BJI were collected consecutively (2011–2016) and tested for susceptibility by broth microdilution methods.Results
S. aureus (64.0%) was the most common pathogen associated with BJI, followed by BHS (13.1%) and CoNS (12.8%). All S. aureus (33.3% meticillin-resistant) isolates were susceptible to dalbavancin, linezolid and vancomycin, while daptomycin and clindamycin showed susceptibility rates of 99.5% and 89.0%, respectively. The minimum inhibitory concentration (MIC) results for dalbavancin were at least eight-fold lower than these comparators against all S. aureus. Dalbavancin was the most potent agent against CoNS (63.1% meticillin-resistant), followed by daptomycin, linezolid and vancomycin. All E. faecalis isolates were inhibited by dalbavancin at ≤0.25?mg/L (US Food and Drug Administration susceptibility breakpoint), except for three vancomycin-resistant isolates. High susceptibility rates for ampicillin (98.8%), daptomycin (100.0%), linezolid (100.0%) and vancomycin (95.1%) were obtained against E. faecalis. Dalbavancin was very active against BHS (MIC90 ≤0.03?µg/mL), and was the most active agent against VGS (highest MIC ≤0.06?mg/L). Ceftriaxone, daptomycin and vancomycin were also active (93.3–100.0% susceptible) against VGS, whereas clindamycin (84.4% susceptible) had marginal activity.Conclusion
Dalbavancin appears to be a viable candidate for treating BJI/osteomyelitis caused by Gram-positive cocci. 相似文献10.
J. Nicholas O&#x;Donnell Nathaniel J. Rhodes Cristina M. Miglis Lejla Catovic Jiajun Liu Cameron Cluff Gwendolyn Pais Sean Avedissian Medha D. Joshi Brooke Griffin Walter Prozialeck Anil Gulati Thomas P. Lodise Marc H. Scheetz 《International journal of antimicrobial agents》2018,51(2):239-243
Background
Although the exposure-dependent efficacy thresholds of vancomycin have been probed, less is known about acute kidney injury (AKI) thresholds for this drug. Sensitive urinary biomarkers, such as kidney injury molecule 1 (KIM-1), have shown high sensitivity and specificity for vancomycin-associated AKI. The aims of the study were to determine if there were dose–response curves with urinary KIM-1, and to evaluate the impact of therapy duration and sex on observed relationships.Methods
A systematic review was conducted via PubMed/MEDLINE. Data were compiled from preclinical studies that reported individual subject data for urinary KIM-1 concentrations, vancomycin dose (mg/kg), duration of treatment, and sex. Sigmoidal Hill-type models were fit to the individual dose-response data.Results
A total of 15 studies were identified, 6 of which reported vancomycin dose and KIM-1 data. Of these, three included individual animal-level data suitable for analysis. For all pooled rats, increasing total daily vancomycin doses displayed a dose-response curve with urinary KIM-1 concentrations (50% maximal toxic response=130.4?mg/kg/day). Dose-response curves were shifted left for females vs. males (P?=?0.05) and for long (i.e. ≥7 days) vs. short (i.e. <4 days) duration of vancomycin therapy (P=0.02).Conclusions
The collective findings demonstrate a clear dose–response relationship between vancomycin dose and AKI. As these analyses focused exclusively on dose-response relationships, additional preclinical data are needed to more clearly define vancomycin exposures that predict the onset of AKI. 相似文献11.
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12.
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13.
Alejandro Pérez-Pitarch Rafael Ferriols-Lisart Gerardo Aguilar Carlos Ezquer-Garín F. Javier Belda Beatriz Guglieri-López 《International journal of antimicrobial agents》2018,51(1):115-121
Introduction
The study objective was to evaluate the efficacy of different dosages of caspofungin in the treatment of invasive candidiasis and aspergillosis, in relation to the probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment, using modelling and Monte Carlo simulations in critically ill adult patients on continuous haemodiafiltration.Methods
Critically ill adult patients on continuous venovenous haemodiafiltration treated with caspofungin were analysed. A population PK model was developed. Four caspofungin dosing regimens were simulated: the licensed regimen, 70 mg/day, 100 mg/day or 200 mg/day. A PK/PD target was defined as the ratio between the area under the caspofungin concentration-time curve over 24 hours and the minimal inhibitory concentration (AUC/MIC) for candidiasis or the minimal effective concentrations (AUC/MEC) for Aspergillus spp. Target attainment based on preclinical target for Candida and Aspergillus was assessed for different MIC or MEC, respectively.Results
Concentration-time data were described by a two-compartment model. Body–weight and protein concentration were the only covariates identified by the model. Goodness-of-fit plots and bootstrap analysis proved the model had a satisfactory performance. As expected, a higher maintenance dose resulted in a higher exposure. Target attainment was >90% for candidiasis (MIC≤0.06 mg/L) and aspergillosis (MEC≤0.5 mg/L), irrespective of the dosing regimen, but not for C. parapsilosis. Standard regimen was insufficient to reach the target for C. albicans and C. parapsilosis with MIC≥0.1 mg/L.Conclusion
The licensed regimen of caspofungin is insufficient to achieve the PK/PD targets in critically ill patients on haemodiafiltration. The determination of MICs will enable dose scheme selection. 相似文献14.
Ezgi Öztaş Alejandro Parejo Garcia-Saavedra Fatih Yanar Beyza Özçinar Nihat Aksakal Sevim Purisa Gül Özhan 《Saudi Pharmaceutical Journal》2018,26(2):274-278
Objectives
P-glycoprotein (P-gp) contributes to the disposition of a wide variety of drugs; therefore, single nucleotide polymorphisms (SNPs) in the P-gp coding gene might affect its activity. It is well known that personalized medicine, instead of empirical treatment, is a clinically important approach for enhancing responses among patients. Indeed, there is a need to evaluate the association between SNPs of P-gp encoded multidrug resistance genes (MDR1, ABCB1), and the dosage requirements of these drugs. In the present study, we evaluated the association between the dosage of Levothyroxine (L-T4) and three common SNPs (C1236T, G2677T/A and C3435T).Methods
Genotyping was done using a real-time PCR platform with DNA samples isolated from the venous blood of ninety post thyroidectomy hypothyroid patients. Thyroid hormone levels were measured as routine biochemistry laboratories in the Medical School of Istanbul University.Results
In the genotype analysis, the minor allele frequencies were 0.48 for C1236T, 0.51 for G2677T/A, and 0.51 for C3435T. In the haplotype-based analysis, T1236T2677T3435 and C1236G2677C3435 were observed as major haplotypes (50.2 and 32.6%, respectively), in agreement with previous studies. The administered dose of L-T4 to achieve physiological thyroid hormone levels was found to be similar in all genotypes and haplotypes, indicating that there is no significant association between MDR1 polymorphisms and L-T4 doses.Conclusion
Because of conflicted previous reports about the genetic contribution of MDR1 polymorphisms to drug disposition, further studies with large numbers of participants are required to clarify this influence. 相似文献15.
Background
Bacterial infections in pediatric patients with leukemia are associated with increased risks for morbidity and mortality. Few Recommendations have been made on the use of antibacterial prophylaxis in pediatrics with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).Objectives
To determine the role of antibacterial prophylaxis in pediatric patients with leukemia and the most appropriate regimen that can be safely and effectively used.Methods
Literature search was conducted independently by 3 reviewers to find studies on the safety and effectiveness of antibacterial prophylactic regimens.Results
The search strategy resulted in 13 studies; most of them were observational studies. The available evidence recommends use of antibiotics with Gram-positive bacterial coverage in AML patients. In ALL patients, prophylaxis was used during the intensive phases of chemotherapy with ciprofloxacin being recommended most commonly.Conclusion
Antibacterial prophylaxis mainly with coverage against Gram-positive bacteria is recommended in pediatric patients with AML. For ALL patients, prophylaxis may be considered for patients who are undergoing intensive chemotherapy phases and are at high risk for infections with ciprofloxacin being the most commonly used agent. In general more studies are needed to determine the role of antibacterial prophylaxis in pediatric patients with leukemia. 相似文献16.
Michele Bartoletti Sara Tedeschi Renato Pascale Luigi Raumer Alberto Enrico Maraolo Giulia Palmiero Fabio Tumietto Francesco Cristini Simone Ambretti Maddalena Giannella Russell Edward Lewis Pierluigi Viale 《International journal of antimicrobial agents》2018,51(3):516-521
Objectives
We hypothesised that treatment with a tigecycline-based antimicrobial regimen for intra–abdominal infection (IAI) could be associated with lower rates of subsequent carbapenem-resistant Enterobacteriaceae (CRE) colonisation or Clostridium difficile infection (CDI) compared with a meropenem-based regimen.Methods
We performed a retrospective, single-centre, matched (1:1) cohort analysis of all patients who received at least 5 days of empirical or targeted tigecycline (TIG)- or meropenem (MER)-based treatment regimens for IAI over a 50-month period. Patients with previous CRE colonisation and CDI were excluded. Risk factors for CRE and CDI were assessed with a Cox regression model that included treatment duration as a time-dependent variable. Thirty-day mortality was assessed with Kaplan-Meier curves.Results
We identified 168 TIG-treated and 168 MER-treated patients. The cumulative incidence rate ratio of CDI was 10-fold lower in TIG-treated vs. MER-treated patients (incidence rate ratio [IRR] 0.10/1000 patient-days, 95%CI 0.002–0.72, P?=?0.007), but similar incidence rates were found for CRE colonisation (IRR 1.39/1000 patient-days, 95%CI 0.68–2.78, P?=?0.36). In a multivariate Cox regression model, the receipt of a TIG- vs. MER-based regimen was associated with significantly lower rates of CDI (HR 0.07, 95%CI 0.03–0.71, P?=?0.02), but not CRE (HR 1.12, 95% CI 0.45–2.83, P?=?0.80). All-cause 30-day mortality was similar in the two groups (P?=?0.46).Conclusion
TIG-based regimens for IAI were associated with a 10-fold lower incidence of CDI compared with MER-based regimens, but there was no difference in the incidence of CRE colonisation. 相似文献17.
Maddalena Giannella Enrico Maria Trecarichi Daniele Roberto Giacobbe Francesco Giuseppe De Rosa Matteo Bassetti Alessandro Bartoloni Michele Bartoletti Angela Raffaella Losito Valerio del Bono Silvia Corcione Sara Tedeschi Francesca Raffaelli Carolina Saffioti Teresa Spanu Gian Maria Rossolini Anna Marchese Simone Ambretti Roberto Cauda Mario Tumbarello 《International journal of antimicrobial agents》2018,51(2):244-248
Objectives
To evaluate the impact of high-dose (HD) carbapenem-based combination therapy on clinical outcome in patients with monomicrobial carbapenem-resistant Klebsiella pneumoniae (CR-KP) bloodstream-infection (BSI).Methods
Post hoc analysis of all adult patients with CR-KP BSI who were treated with a combination antibiotic regimen, collected over a six-year period in six large Italian teaching hospitals. To control for confounding effects of HD carbapenem combination on 14-day mortality, a multivariate Cox regression analysis was performed. Due to imbalances between patients, a propensity score for receiving HD carbapenem was added to the model.Results
595 patients with CR-KP BSI were analysed, 77% of isolates showed a carbapenem MIC ≥16?mg/L, 428 (71.9%) received HD carbapenem-based combination therapy. Overall, 127 patients (21.3%) died within 14 days after BSI onset. Multivariate analysis showed the Charlson comorbidity index (HR 1.31, 95%CI 1.20–1.43, P?<0.001), septic shock at BSI onset (HR 3.14, 95%CI 2.19–4.50, P?<0.001), and colistin-resistant strain (HR 1.52, 95%CI 1.02–2.24, P?=?0.03) were independently associated with 14-day mortality, whereas admission to surgical ward (HR 0.44, 95%CI 0.25–0.78, P?=?0.005) and HD carbapenem use (HR 0.69, 95%CI 0.47–1.00, P?=?0.05) were protective factors. When adjusted for the propensity score, HD carbapenem use showed a greater protective effect (HR 0.64, 95%CI 0.43–0.95, P?=?0.03). Stratifying the model for carbapenem MIC, the benefit of HD carbapenem was also observed for strains with carbapenem MIC ≥16?mg/L.Conclusions
In patients receiving combination therapy for CR-KP BSI, the use of HD carbapenem seems to be associated with better outcome, even in the presence of high-level carbapenem resistance. 相似文献18.
Sharad?Mangal Haichen?Nie Rongkun?Xu Rui?Guo Alex?Cavallaro Dmitry?Zemlyanov Qi??Zhou 《Pharmaceutical research》2018,35(2):28
Purpose
Inhalation therapy is popular to treat lower respiratory tract infections. Azithromycin is effective against some bacteria that cause respiratory tract infections; but it has poor water solubility that may limit its efficacy when administrated as inhalation therapy. In this study, dry powder inhaler formulations were developed by co-spray drying azithromycin with L-leucine with a purpose to improve dissolution.Methods
The produced powder formulations were characterized regarding particle size, morphology, surface composition and in-vitro aerosolization performance. Effects of L-leucine on the solubility and in-vitro dissolution of azithromycin were also evaluated.Results
The spray dried azithromycin alone formulation exhibited a satisfactory aerosol performance with a fine particle fraction (FPF) of 62.5?±?4.1%. Addition of L-leucine in the formulation resulted in no significant change in particle morphology and FPF, which can be attributed to enrichment of azithromycin on the surfaces of composite particles. Importantly, compared with the spray-dried amorphous azithromycin alone powder, the co-spray dried powder formulations of azithromycin and L-leucine demonstrated a substantially enhanced in-vitro dissolution rate. Such enhanced dissolution of azithromycin could be attributed to the formation of composite system and the acidic microenvironment around azithromycin molecules created by the dissolution of acidic L-leucine in the co-spray dried powder. Fourier transform infrared spectroscopic data showed intermolecular interactions between azithromycin and L-leucine in the co-spray dried formulations.Conclusions
We developed the dry powder formulations with satisfactory aerosol performance and enhanced dissolution for a poorly water soluble weak base, azithromycin, by co-spray drying with an amino acid, L-leucine.19.
Alexis Viel Jérôme Henri Salim Bouchène Julian Laroche Jean-Guy Rolland Jacqueline Manceau Michel Laurentie William Couet Nicolas Grégoire 《Pharmaceutical research》2018,35(5):92