scholarly journals Optimizing Aminoglycoside Therapy for Nosocomial Pneumonia Caused by Gram-Negative Bacteria

1999 ◽  
Vol 43 (3) ◽  
pp. 623-629 ◽  
Author(s):  
Angela D. M. Kashuba ◽  
Anne N. Nafziger ◽  
George L. Drusano ◽  
Joseph S. Bertino
Keyword(s):  
Nosocomial Pneumonia ◽  
Therapeutic Response ◽  
Leukocyte Count ◽  
Gram Negative Bacteria ◽  
Regression Analyses ◽  
Temperature Resolution ◽  
Gram Negative ◽  
Aminoglycoside Therapy ◽  
Days Of Therapy ◽  
Institutional Expenditures

ABSTRACT Nosocomial pneumonia is a notable cause of morbidity and mortality and leads to increases in lengths of hospital stays and institutional expenditures. Aminoglycosides are used to treat patients with these infections, but few data on the doses and schedules required to achieve optimal therapeutic outcomes exist. We analyzed aminoglycoside treatment data for 78 patients with nosocomial pneumonia to determine if optimization of aminoglycoside pharmacodynamic parameters results in a more rapid therapeutic response (defined by outcome and days to leukocyte count resolution and temperature resolution). Cox proportional hazards, Classification and Regression Tree (CART), and logistic regression analyses were applied to the data. By all analyses, the first measured maximum concentration of drug in serum (C max)/MIC predicted days to temperature resolution and the second measured C max/MIC predicted days to leukocyte count resolution. For days to temperature resolution and leukocyte count resolution, CART analyses produced breakpoints, with an 89% success rate at 7 days of therapy for aC max/MIC of >4.7 and an 86% success rate at 7 days of therapy for a C max/MIC of >4.5, respectively. Logistic regression analyses predicted a 90% probability of temperature resolution and leukocyte count resolution by day 7 if aC max/MIC of ≥10 is achieved within the first 48 h of aminoglycoside therapy. Aggressive aminoglycoside dosing immediately followed by individualized pharmacokinetic monitoring would ensure that C max/MIC targets are achieved early in therapy. This would increase the probability of a rapid therapeutic response for pneumonia caused by gram-negative bacteria and potentially decreasing durations of parenteral antibiotic therapy, lengths of hospitalization, and institutional expenditures, a situation in which both the patient and the institution benefit.

scholarly journals The Impact of Risk Factors on Treatment Outcomes of Nosocomial Pneumonia Due to Gram-Negative Bacteria in the Intensive Care Unit

2021 ◽  
Author(s):  
Thu Vo-Pham-Minh ◽  
Van Duong-Thi-Thanh ◽  
Thang Nguyen ◽  
Quyen Phan-Tran-Xuan ◽  
Hoang Phan-Thi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Intensive Care Unit ◽  
Intensive Care ◽  
Treatment Outcomes ◽  
Nosocomial Pneumonia ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
The Impact

scholarly journals Clinical pharmacokinetics of 3-h extended infusion of meropenem in adult patients with severe sepsis and septic shock: implications for empirical therapy against Gram-negative bacteria

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Amol T. Kothekar ◽  
Jigeeshu Vasishtha Divatia ◽  
Sheila Nainan Myatra ◽  
Anand Patil ◽  
Manjunath Nookala Krishnamurthy ◽  
...  
Keyword(s):  
Septic Shock ◽  
Severe Sepsis ◽  
Modeling And Simulation ◽  
Empirical Therapy ◽  
Gram Negative Bacteria ◽  
Clinical Pharmacokinetics ◽  
Gram Negative ◽  
Arterial Blood ◽  
Days Of Therapy ◽  
Extended Infusion

Abstract Background Optimal anti-bacterial activity of meropenem requires maintenance of its plasma concentration (Cp) above the minimum inhibitory concentration (MIC) of the pathogen for at least 40% of the dosing interval (fT > MIC > 40). We aimed to determine whether a 3-h extended infusion (EI) of meropenem achieves fT > MIC > 40 on the first and third days of therapy in patients with severe sepsis or septic shock. We also simulated the performance of the EI with respect to other pharmacokinetic (PK) targets such as fT > 4 × MIC > 40, fT > MIC = 100, and fT > 4 × MIC = 100. Methods Arterial blood samples of 25 adults with severe sepsis or septic shock receiving meropenem 1000 mg as a 3-h EI eight hourly (Q8H) were obtained at various intervals during and after the first and seventh doses. Plasma meropenem concentrations were determined using a reverse-phase high-performance liquid chromatography assay, followed by modeling and simulation of PK data. European Committee on Antimicrobial Susceptibility Testing (EUCAST) definitions of MIC breakpoints for sensitive and resistant Gram-negative bacteria were used. Results A 3-h EI of meropenem 1000 mg Q8H achieved fT > 2 µg/mL > 40 on the first and third days, providing activity against sensitive strains of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. However, it failed to achieve fT > 4 µg/mL > 40 to provide activity against strains susceptible to increased exposure in 33.3 and 39.1% patients on the first and the third days, respectively. Modeling and simulation showed that a bolus dose of 500 mg followed by 3-h EI of meropenem 1500 mg Q8H will achieve this target. A bolus of 500 mg followed by an infusion of 2000 mg would be required to achieve fT > 8 µg > 40. Targets of fT > 4 µg/mL = 100 and fT > 8 µg/mL = 100 may be achievable in two-thirds of patients by increasing the frequency of dosing to six hourly (Q6H). Conclusions In patients with severe sepsis or septic shock, EI of 1000 mg of meropenem over 3 h administered Q8H is inadequate to provide activity (fT > 4 µg/mL > 40) against strains susceptible to increased exposure, which requires a bolus of 500 mg followed by EI of 1500 mg Q8H. While fT > 8 µg/mL > 40 require escalation of EI dose, fT > 4 µg/mL = 100 and fT > 8 µg/mL = 100 require escalation of both EI dose and frequency.

scholarly journals Changes in Domestic Animals After Endotoxin Administration a Review

2014 ◽  
Vol 14 (3) ◽  
pp. 479-489 ◽  
Author(s):  
Janusz Danek ◽  
Urszula Żurek
Keyword(s):  
Lipid A ◽  
Clinical Symptoms ◽  
Leukocyte Count ◽  
Domestic Animals ◽  
Target Cells ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Endotoxin Exposure ◽  
Activated Neutrophils ◽  
As Effects

Abstractgram-negative bacteria. Lipopolysaccharides are complex glycolipids composed of lipid A, a core polysaccharide, and repeating units of O-specific polysaccharides. Lipid A is associated with the majority of toxic effects of gram-negative bacteria. It interacts with target cells, such as macrophages and activated neutrophils, initiating the inflammatory cascade. The effects of LPS depend mostly on organism reaction to endotoxins, their concentration in blood and also on the state of the animal before the occurrence of endotoxemia. The effect of endotoxin on the reproductive functions of domestic animals has been partly elucidated. This paper presents data on clinical, hematological and biochemical changes in endotoxemia as well as effects of injection of endotoxin in the reproductive systems in boars, rams, and stallions. The results show that these males respond to endotoxins in a similar way, concerning clinical symptoms, body temperature and leukocyte count in blood. Endocrine and seminal changes are different and the range of these changes also depends on the dose and endotoxin exposure time.

Nosocomial pneumonia

2020 ◽  
pp. 4022-4026
Author(s):  
Wei Shen Lim
Keyword(s):  
Staphylococcus Aureus ◽  
Intensive Care ◽  
Nosocomial Infection ◽  
Nosocomial Pneumonia ◽  
Upper Airway ◽  
Pulmonary Infiltrate ◽  
General Ward ◽  
Healthy People ◽  
Gram Negative Bacteria ◽  
Gram Negative

Nosocomial pneumonia is generally defined as a new pulmonary infiltrate on chest radiography, combined with evidence of infection expressed as fever, purulent respiratory secretions, and/or leucocytosis, with onset 48 hours or more after admission. It is the most frequent lethal nosocomial infection (overall mortality 7% in general ward inpatients to over 50% in critically ill patients). Most cases are caused by Gram-negative bacteria (50–70%) or Staphylococcus aureus (15–30%). Gram-negative bacteria reach the lung by aspiration of gastric contents or by microaspiration of upper airway secretions; throat cultures reveal that 60–75% of patients on intensive care units are colonized by these organisms (compared to 2–6% of healthy people).

scholarly journals The Potential Role of Aerosolized Colistin in the Ventilator-Associated Pneumonia Management Caused by Multidrug-Resistant Gram-Negative Bacteria: A Randomized Clinical Trial

2021 ◽  
Author(s):  
Faezeh Feizabadi ◽  
Seyed Mohammad Reza Hashemian ◽  
Zahra Mirshafiei ◽  
Farzaneh Dastan
Keyword(s):  
Clinical Trial ◽  
Randomized Clinical Trial ◽  
Multidrug Resistant ◽  
Sputum Culture ◽  
Control Group ◽  
Gram Negative Bacteria ◽  
Ventilator Associated Pneumonia ◽  
Gram Negative ◽  
Days Of Therapy ◽  
Negative Sputum

Background: Infections caused by multidrug-resistant (MDR) pathogen have caused a resurgence of interest in colistin. To date, information about the effectiveness of Aerosolized Colistin (AS) is very limited in the treatment of Ventilator-Associated Pneumonia (VAP). The aim of this study is to evaluate the efficacy and safety of AS in conjunction with intravenous (IV) colistin in patients with VAP, caused by MDR Gram-Negative Bacteria (GNB). Methods: This parallel randomized clinical trial was conducted on patients with VAP in the Intensive Care Unit (ICU) ward. 27 patients allocated to the intervention or the control group. Patients in the intervention group received IV Colistin based on glomerular filtration rate along with aerosolized Colistin, 2 million units three times a day. In the control group, only IV Colistin was administered. For all patients, Procalcitonin (PCT), sputum culture, and Clinical Pulmonary Infection Score (CPIS) were evaluated and compared as outcome measures at the specified period of time. Results: Negative sputum culture was achieved in 9 (80%) out of 11 patients in the AS-IV Colistin group after seven days of therapy versus 9 (56.25%) out of 16 in the control group (P= 0.01). PCT and CPIS scores were not significantly different between two groups (P=0.21, P= 0.62). Furthermore, nephrotoxicity and neurotoxicity were not seen. Conclusion: AS Colistin lead to earlier negative sputum culture without increasing risk of nephrotoxicity and neurotoxicity, and could potentially be a beneficial adjunctive approach in the management of MDR-VAP.

scholarly journals Association between fluoroquinolone utilization rates and susceptibilities of gram-negative bacilli: Results from an 8-year intervention by an antibiotic stewardship program in an inner-city United States hospital

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110118
Author(s):  
Cosmina Zeana ◽  
Frank E. Palmieri ◽  
Vikas Gupta ◽  
Gang Ye ◽  
Peter Lao ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Proteus Mirabilis ◽  
Community Hospital ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Stewardship Program ◽  
Days Of Therapy ◽  
Empiric Antibiotic

This study evaluated an antibiotic stewardship program (ASP) intervention aimed at reducing inpatient fluoroquinolone (FQ) use and examined its impact on ciprofloxacin susceptibilities of gram-negative bacteria in a large 611-bed community hospital. A two-step ASP intervention was implemented: an electronic medical record algorithm that prompted physicians to re-evaluate FQ use shortly after admission and changed institutional UTI/pneumonia guidelines that recommended options alternate to FQs for first-line empiric antibiotic therapy in 2010 and 2011 respectively. Between 2007 and 2017 FQ use and ciprofloxacin susceptibilities of all non-duplicate cultured isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa obtained ≥72 h after admission were reviewed. Ambulatory care isolates served as a comparison group. FQ utilization rates and relationships to ciprofloxacin susceptibility were evaluated using interrupted time series models. Over the 11-year period, FQ use decreased from 110.0 (2007) to 26.2 (2017) days of therapy/1000 days at risk ( p < 0.001). Compared to pre-intervention, the estimated (post-intervention) reduction in FQ utilization was 28.4 (95% CI: 10.9–46) days of therapy/1000 days at risk. Reduced FQ utilization was correlated with increase susceptibilities to ciprofloxacin of hospital onset isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis ( p < 0.02), and Pseudomonas aeruginosa ( p = 0.07). No significant susceptibility change was observed in the ambulatory care isolates. Persuasive interventions by an ASP successfully modified physicians’ inpatient empiric antibiotic use, produced a sustained reduction in FQ utilization rates and increased ciprofloxacin susceptibility to four commonly encountered gram-negative bacteria in a community hospital.

The Outcome of Modified St. Jude Total XV Protocol in Turkish Children with Newly Diagnosed Acute Lymphoblastic Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2590-2590
Author(s):  
Hulya Yilmaz ◽  
Selin Aytac ◽  
Barış Kuşkonmaz ◽  
Duygu Çetinkaya ◽  
Sule Unal ◽  
...  
Keyword(s):  
Leukocyte Count ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Remission Induction ◽  
Gram Negative Bacteria ◽  
Newly Diagnosed ◽  
Turkish Children ◽  
Gram Negative ◽  
Blast Count ◽  
Total Therapy

Introduction: Childhood acute lymphoblastic leukemia (ALL) treatment with St. Jude Total therapies showed superior outcome with event-free and overall survival rates 85.6 ± 2.9% and 93.5 ± 1.9%, respectively. Here, we studied prognostic features and the outcome of Turkish children with newly diagnosed ALL treated with modified St. Jude Total Therapy XV Protocol. Patients and methods: There were 182 newly diagnosed ALL patients aged 1-18 years old and treated with modified Total Therapy XV between 1 January 2008 and 30 January 2016. According to our previous successful results with high dose methylprednisolone (HDMP), each patient received 7 days of HDMP as an initial treatment and randomized at doses of 20 mg/kg/d or 10mg/kg/d HDMP, not exceeding at maximum 1000 mg MP. After the first 7-day steroid treatment, concomitant chemotherapy was given and the steroid doses were tapered to 10mg/kg/d and 5mg/kg/d during the next week in each group, respectively. Afterwards, the whole group received 2 mg/kg/d MP for the following two weeks. Also, there were a third group received lower doses (<10 mg/kg/d) of MP because of the hyperleukocytosis for the first 7 days. Results: Out of 182 patients, 174 completed the treatment and 1 patient experienced induction failure, 4 patients died during remission induction, 3 patients abandoned treatment during maintenance. 97.2% of the children entered complete remission after remission induction. 16 patients (8.9%) had relapses during follow-up, 9 isolated bone marrow, 7 isolated CNS and 3 of 7 patients who had CNS relapse experienced a second relapse (bone marrow) afterwards. The five-year event-free survival (EFS) and overall survival (OS) were 85.6±2.6 % and 89.2±2.3%, respectively. There was no significant difference according to the survival rates between different MP doses (10 and 20mg/kg/d) which were given before induction. Moreover, difference in frequency of infection between patient groups treated with different steroid doses during induction period was not found statistically significant. Univarite analysis showed that age ≥ 10 years at the time of diagnosis, initial leukocyte count ≥50x109/L, low MP doses (<10mg/kg/d) and infection with gram negative bacteria during remission induction were associated with inferior EFS. Multivariate analysis revealed lower EFS rates with an initial leukocyte count ≥50x109/L [HR=5.58, 95% CI: 1.99-15.64, p<0.001], age ≥ 10 years at the time of diagnosis [HR=3.81, 95% CI: 1.65-8.81, p=0.002], infection with gram negative bacteria during remission induction [HR=3.71, 95% CI: 1.55-8.88, p=0.003] and CD20 positivity (>20%) at diagnosis [HR=2.49, 95% CI: 1.08-5.73, p=0.031]. Response to MP measured as <1000/mm3absolute blast count in peripheral blood sample after first 7 days did not have statistically significant influence on survival in comparison with poor MP response (<1000/mm3absolute blast count in peripheral blood). Conclusion: Our encouraging EFS result with modified St. Jude Total XV in childhood ALL patients is comparable with the one in original protocol. Favorable effect of higher doses of MP (20 mg/kg/d) on survival could not be demonstrated when compared with 10mg/kg/d. Disclosures No relevant conflicts of interest to declare.

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