High-Dose Continuous Oxacillin Infusion Results in Achievement of Pharmacokinetics Targets in Critically Ill Patients with Deep Sternal Wound Infections following Cardiac Surgery

ABSTRACTKnowledge regarding antimicrobial therapy strategies in deep sternal wound infections (DSWI) following cardiac surgery is limited. Therefore, we aimed to determine the steady-state plasma and mediastinal concentrations of oxacillin administered by continuous infusion in critically ill patients with DSWI and to compare these concentrations with the susceptibility of staphylococci recovered. A continuous infusion of oxacillin (150 to 200 mg/kg of body weight/24 h) was administered after a loading dose (50 mg/kg). Plasma and mediastinal concentrations of total and unbound oxacillin were determined 4 h after the loading dose (H4) and then at day 1 (H24) and day 2 (H48). Twelve patients were included. Nine patients exhibited bacteremia, 5 were in septic shock, 8 were positive forStaphylococcus aureus, and 4 were positive for coagulase-negative staphylococci. The median MIC (first to third interquartile range) was 0.25 (0.24 to 0.41) mg/liter. Median plasma concentrations of total and unbound oxacillin at H4, H24, and H48 were, respectively, 64.4 (41.4 to 78.5) and 20.4 (12.4 to 30.4) mg/liter, 56.9 (31.4 to 80.6) and 21.7 (6.5 to 27.3) mg/liter, and 57.5 (32.2 to 85.1) and 20 (14.3 to 35.7) mg/liter. The median mediastinal concentrations of total and unbound oxacillin at H4, H24, and H48 were, respectively, 2.3 (0.7 to 25.9) and 0.9 (<0.5 to 15) mg/liter, 29.1 (19.7 to 38.2) and 12.6 (5.9 to 19.8) mg/liter, and 31.6 (14.9 to 42.9) and 17.1 (6.7 to 26.7) mg/liter. High-dose oxacillin delivered by continuous infusion is a valuable strategy to achieve our pharmacokinetic target (4× MIC) at the site of action at H24. But concerns remain in cases of higher MICs, emphasizing the need for clinicians to obtain the MICs for the bacteria and to monitor oxacillin concentrations, especially the unbound forms, at the target site.

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Adding Vancomycin to Perioperative Prophylaxis Decreases Deep Sternal Wound Infections in High-risk Cardiac Surgery Patients

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0036-1571550 ◽

2016 ◽

Vol 64 (S 01) ◽

Author(s):

S. Reineke ◽

B. Gahl ◽

U. Führer ◽

C. Seidl ◽

M. Bächli ◽

...

Keyword(s):

Cardiac Surgery ◽

High Risk ◽

Wound Infections ◽

Perioperative Prophylaxis ◽

Sternal Wound Infections ◽

Deep Sternal Wound Infections

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Deep Sternal Wound Infections After Cardiac Surgery: A New Australian Tertiary Centre Experience

Heart Lung and Circulation ◽

10.1016/j.hlc.2020.02.003 ◽

2020 ◽

Vol 29 (10) ◽

pp. 1571-1578 ◽

Cited By ~ 1

Author(s):

Umar Ali ◽

Liam Bibo ◽

Madison Pierre ◽

Nicholas Bayfield ◽

Lior Raichel ◽

...

Keyword(s):

Cardiac Surgery ◽

Wound Infections ◽

Tertiary Centre ◽

Sternal Wound Infections ◽

Deep Sternal Wound Infections

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Tigecycline Therapy for Nosocomial Pneumonia due to Carbapenem-Resistant Gram-Negative Bacteria in Critically Ill Patients Who Received Inappropriate Initial Antibiotic Treatment: A Retrospective Case Study

BioMed Research International ◽

10.1155/2016/8395268 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Xiaomai Wu ◽

Yefei Zhu ◽

Qiuying Chen ◽

Liuyang Gong ◽

Jian Lin ◽

...

Keyword(s):

Mortality Rate ◽

Critically Ill ◽

Nosocomial Pneumonia ◽

Critically Ill Patients ◽

Standard Dose ◽

High Dose ◽

Gram Negative Bacteria ◽

Loading Dose ◽

Icu Mortality ◽

Carbapenem Resistant

Background. Nosocomial pneumonia due to carbapenem-resistant Gram-negative bacteria (CRGNB) is a growing concern because treatment options are limited and the mortality rate is high. The effect of tigecycline (TGC) on nosocomial pneumonia due to CRGNB in patients who have received inappropriate initial empiric antibiotic treatment (IIAT) is unclear. Therefore, this study aimed to examine the effect of TGC on nosocomial pneumonia due to CRGNB in critically ill patients who had received IIAT. Methods. A retrospective study was conducted in an adult respiratory intensive care unit. Data were obtained and analyzed for all patients who were treated with TGC ≥ 3 days for microbiologically confirmed nosocomial pneumonia due to CRGNB and had experienced initial antibiotic failure. Clinical and microbiological outcomes were investigated. Results. Thirty-one patients with hospital-acquired pneumonia or ventilator-associated pneumonia were included in the study. The majority of the responsible organisms were carbapenem-resistant Acinetobacter baumannii (67.7%), followed by Klebsiella pneumoniae (16.1%) and Escherichia coli (9.7%). Twenty patients were treated with high-dose TGC therapy (100 mg every 12 h after a 200 mg loading dose), and the others received a standard-dose therapy (50 mg every 12 h after a 100 mg loading dose). The duration of TGC therapy was 14.3±2.8 days. The global clinical cure rate and the microbiological eradication rate were 48.4% and 61.3%, respectively. The overall ICU mortality rate was 45.2%. A higher score on the Acute Physiology and Chronic Health Evaluation II and a longer duration of IIAT were associated with clinical failure. High-dose TGC therapy had a higher clinical success rate [65.0% (13/20) versus 18.2% (2/11), P=0.023] and a lower ICU mortality rate [30.0% (6/20) versus 72.7% (8/11), P=0.031] than the standard-dose therapy. Conclusions. TGC, especially a high-dose regimen, might be a justifiable option for critically ill patients with nosocomial pneumonia due to CRGNB who have received IIAT when the options for these patients are limited.

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Copeptin and Arginine Vasopressin Concentrations in Critically Ill Patients

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-2830 ◽

2006 ◽

Vol 91 (11) ◽

pp. 4381-4386 ◽

Cited By ~ 90

Author(s):

Stefan Jochberger ◽

Nils G. Morgenthaler ◽

Viktoria D. Mayr ◽

Günter Luckner ◽

Volker Wenzel ◽

...

Keyword(s):

Cardiac Surgery ◽

Healthy Volunteers ◽

Critically Ill ◽

Arginine Vasopressin ◽

Critically Ill Patients ◽

Plasma Concentrations ◽

University Teaching ◽

Surgical Intensive Care Unit ◽

Surgical Intensive Care ◽

Icu Patients

Abstract Context: Determination of arginine vasopressin (AVP) concentrations may be helpful to guide therapy in critically ill patients. A new assay analyzing copeptin, a stable peptide derived from the AVP precursor, has been introduced. Objective: Our objective was to determine plasma copeptin concentrations. Design: We conducted a post hoc analysis of plasma samples and data from a prospective study. Setting: The setting was a 12-bed general and surgical intensive care unit (ICU) in a tertiary university teaching hospital. Patients: Our subjects were 70 healthy volunteers and 157 ICU patients with sepsis, with systemic inflammatory response syndrome (SIRS), and after cardiac surgery. Interventions: There were no interventions. Main Outcome Measures: Copeptin plasma concentrations, demographic data, AVP plasma concentrations, and a multiple organ dysfunction syndrome score were documented 24 h after ICU admission. Results: AVP (P < 0.001) and copeptin (P < 0.001) concentrations were significantly higher in ICU patients than in controls. Patients after cardiac surgery had higher AVP (P = 0.003) and copeptin (P = 0.003) concentrations than patients with sepsis or SIRS. Independent of critical illness, copeptin and AVP correlated highly significantly with each other. Critically ill patients with sepsis and SIRS exhibited a significantly higher ratio of copeptin/AVP plasma concentrations than patients after cardiac surgery (P = 0.012). The American Society of Anesthesiologists’ classification (P = 0.046) and C-reactive protein concentrations (P = 0.006) were significantly correlated with the copeptin/AVP ratio. Conclusions: Plasma concentrations of copeptin and AVP in healthy volunteers and critically ill patients correlate significantly with each other. The ratio of copeptin/AVP plasma concentrations is increased in patients with sepsis and SIRS, suggesting that copeptin may overestimate AVP plasma concentrations in these patients.

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Adding vancomycin to perioperative prophylaxis decreases deep sternal wound infections in high-risk cardiac surgery patients

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezx328 ◽

2017 ◽

Vol 53 (2) ◽

pp. 428-434 ◽

Cited By ~ 11

Author(s):

Sylvia Reineke ◽

Thierry P Carrel ◽

Verena Eigenmann ◽

Brigitta Gahl ◽

Urs Fuehrer ◽

...

Keyword(s):

Cardiac Surgery ◽

High Risk ◽

Wound Infections ◽

Perioperative Prophylaxis ◽

Sternal Wound Infections ◽

Deep Sternal Wound Infections

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New Colistin Population Pharmacokinetic Data in Critically Ill Patients Suggesting an Alternative Loading Dose Rationale

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03508-14 ◽

2014 ◽

Vol 58 (12) ◽

pp. 7324-7330 ◽

Cited By ~ 50

Author(s):

N. Grégoire ◽

O. Mimoz ◽

B. Mégarbane ◽

E. Comets ◽

D. Chatelier ◽

...

Keyword(s):

Steady State ◽

Critically Ill ◽

Critically Ill Patients ◽

Plasma Concentrations ◽

Multidrug Resistant ◽

Pharmacokinetic Analysis ◽

Population Pharmacokinetic ◽

Pharmacokinetic Data ◽

Loading Dose ◽

Liquid Chromatography Tandem Mass

ABSTRACTColistin is an old antibiotic that has recently gained a considerable renewal of interest as the last-line defense therapy against multidrug-resistant Gram-negative bacteria. It is administered as colistin methanesulfonate (CMS), an inactive prodrug, and it was shown that due to slow CMS conversion, colistin plasma concentrations increase very slowly after treatment initiation, which constitutes the rationale for a loading dose in critically ill patients. However, faster CMS conversion was observed in healthy volunteers but using a different CMS brand, which may also have a major impact on colistin pharmacokinetics. Seventy-three critically ill patients not undergoing dialysis received multiple doses of CMS. The CMS concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and a pharmacokinetic analysis was conducted using a population approach. We confirmed that CMS renal clearance and colistin concentrations at steady state are mostly governed by creatinine clearance, but we predict a typical maximum concentration of drug in serum (Cmax) of colistin close to 2 mg/liter, occurring 3 h after an initial dose of 2 million international units (MIU) of CMS. Accordingly, the estimated colistin half-life (t1/2) was relatively short (3.1 h), with rapid attainment of steady state. Our results are only partially consistent with other recently published results. We confirm that the CMS maintenance dose should be adjusted according to renal function in critically ill patients. However, much higher than expected colistin concentrations were observed after the initial CMS dose, with rapid steady-state achievement. These discrepancies challenge the pharmacokinetic rationale for a loading dose, which may still be appropriate for rapid bacterial eradication and an improved clinical cure rate.

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Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia

Journal of Intensive Care Medicine ◽

10.1177/0885066616646551 ◽

2016 ◽

Vol 32 (8) ◽

pp. 487-493 ◽

Cited By ~ 16

Author(s):

Jessica L. Elefritz ◽

Karri A. Bauer ◽

Christian Jones ◽

Julie E. Mangino ◽

Kyle Porter ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Clinical Cure ◽

Statistical Significance ◽

Cohort Analysis ◽

Kidney Injury ◽

Multidrug Resistant ◽

High Dose ◽

Loading Dose ◽

Gram Negative

Introduction: Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. Methods: A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. Results: Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. Conclusion: The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

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Risk factors for deep sternal wound infections after cardiac surgery in Jordan

Journal of Clinical Nursing ◽

10.1111/j.1365-2702.2010.03193.x ◽

2009 ◽

Vol 19 (13-14) ◽

pp. 1873-1881 ◽

Cited By ~ 7

Author(s):

Ibtisam M Al-Zaru ◽

Ali A Ammouri ◽

Mousa A Al-Hassan ◽

Anas A Amr

Keyword(s):

Risk Factors ◽

Cardiac Surgery ◽

Wound Infections ◽

Sternal Wound Infections ◽

Deep Sternal Wound Infections

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Silver-Impregnated Dressing Does Not Decrease Incidence of Surgical Site Infection after Adult Cardiac Surgery

Innovations Technology and Techniques in Cardiothoracic and Vascular Surgery ◽

10.1097/imi.0000000000000538 ◽

2018 ◽

Vol 13 (4) ◽

pp. 296-299

Author(s):

Vignesh Raman ◽

Kelly A. Thompson-Brazill ◽

Kathy Kane ◽

Charles D. Harr ◽

Abdul G. Chaudhry ◽

...

Keyword(s):

Cardiac Surgery ◽

Cohort Study ◽

Wound Infection ◽

Wound Infections ◽

Sternal Wound Infection ◽

Large Cohort Study ◽

Gauze Dressing ◽

Sternal Wound Infections ◽

Adult Cardiac Surgery ◽

Deep Sternal Wound Infections

Objective Sternal wound infections complicate 1% to 8% of cardiac surgeries and carry significant morbidity. We investigated the utility of silver-impregnated dressing in decreasing sternal wound infections after sternotomy cases. Methods A single-institution cohort study was performed as part of a quality improvement trial of a new sternal dressing. Five hundred fifty-seven sternotomy cases were performed in 2015 with application of a traditional gauze dressing. In 2016, 682 sternotomy cases were performed with the use of a commercially available silver-impregnated dressing. Prospectively identified metrics were analyzed for each patient population along with nursing assessments and structured questionnaires. Results Baseline characteristics of patients in traditional gauze and silver-impregnated dressing groups were similar. Morbidity and mortality were similar. Nine (1.6%) and 12 (1.8%) sternal wound infections were reported in traditional gauze and silver-impregnated dressing groups, respectively. There was no difference in the rate of sternal wound infections ( P = 0.80). The number of organ space infections (3) and deep sternal wound infections (3) was the same; however, the number of superficial infections was greater in the silver-impregnated dressing cohort (3 vs. 6). Among patients in either group with sternal wound infection, there were no differences in the proportion of superficial infections (44% vs. 50%, P = 0.8) or the organism cultured (67% vs. 50% staphylococcus, P = 0.45). A total of 22% of patients reported “not satisfied” with silver-impregnated dressing. Conclusions Silver dressings did not reduce sternal wound infection after sternotomy for cardiac surgery in a large-cohort study. We discontinued the routine use of silver dressings for adult cardiac surgery based on these results because traditional gauze likely represents an equally effective and less costly alternative.

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