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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 2  |  Issue : 1  |  Page : 1-7

Comparative study between usage of tazocin/vancomycin versus tazocin/linezolide in treatment of traumatized contused lung


Department of Anesthesia and ICU, Faculty of Medicine, Ain Shams University, Cairo, Egypt; Consultant Intensivist in Intensive Care Depatement, King Abdel Aziz Specialist Hospital, Taif, KSA

Date of Web Publication10-Oct-2018

Correspondence Address:
Mohamed Gaber Ibrahium Mostafa Allam
Department of Anesthesia and ICU, Faculty of Medicine, Ain Shams University, Cairo; King Abdel Aziz Specialist Hospital, Taif

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sccj.sccj_10_18

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  Abstract 


Introduction: Ventilator-associated pneumonia (VAP) is subtype of healthcare acquired pneumonia. With high mortality rate (46%), especially in contused lungs due to trauma. Antibiotics are important in treatment of VAP. Aim of Work: The aim is to evaluate and compare the effect of the use of tazocin (piperacillin + tazobactam)/vancomycin combination versus the use of tazocin/linezolid in the treatment of VAP and weaning from the ventilator in traumatized lungs in patients with severe chest trauma complicated with VAP. Patients and Methods: Prospective double-blind study conducted on 200 patients from King Abdul-Aziz Specialized Hospital. Patients were allocated into two groups as follows: Group A included 100 patients who received piperacillin-tazobactam with vancomycin with the five points of bundle of VAP prevention while Group B included another 100 patients who received piperacillin-tazobactam but with linezolid and with the five points of bundle of VAP prevention. In this study, diagnosis of lung contusion was made by computerized axial tomography of the chest while VAP was diagnosed by modified clinical pulmonary infection score (CPIS). Any patient who had score of 6 or more was considered to have VAP. Results: 15, 38, and 46 patients in Group A showing controlled tracheal secretion, respectively, in three studied period compared to 28, 75, and 83 in Group B, less parenchymatous lung infiltration in the chest X-ray 12, 40, and 48 patients in Group A compared to 24, 88, and 91 patients in Group B, improvement of the hypoxic index 48, 76, and 85 patients in Group A compared to 66, 90, and 98 patients in B, normalization of temperature 16, 36, and 54 patients in Group A while 40, 76, and 90 patients in B and reduction of total leukocytic count 18, 35, and 57 patients in Group A while 38,70, and 87 patients in Group B, there was 15 out of 98 patients in Group A not weaned while only 5 out of 100 patients in Group B cases failed to be weaned from mechanical ventilation within the studied period (2 weeks). Conclusion: The use of tazocin/linezolid provided a rapid response in treatment and less morbidity by shortening the duration of ventilation than tazocin/vancomycin in VAP that occurred in traumatized lungs.

Keywords: Antibiotics VAP contused lung, antibiotics usage in ventilator-associated pneumonia


How to cite this article:
Mostafa Allam MG. Comparative study between usage of tazocin/vancomycin versus tazocin/linezolide in treatment of traumatized contused lung. Saudi Crit Care J 2018;2:1-7

How to cite this URL:
Mostafa Allam MG. Comparative study between usage of tazocin/vancomycin versus tazocin/linezolide in treatment of traumatized contused lung. Saudi Crit Care J [serial online] 2018 [cited 2018 Oct 16];2:1-7. Available from: http://www.sccj-sa.org/text.asp?2018/2/1/1/243012




  Introduction Top


Ventilator-associated pneumonia (VAP) is a sub-type of hospital-acquired pneumonia (HAP) that occurs in patients receiving mechanical ventilation in the Intensive Care Unit (ICU) for more than 48 h of intubation and ventilation. Between 8% and 28% of patients receiving mechanical ventilation are affected by VAP.[1],[2],[3],[4] Hospital mortality of ventilated patients who developed VAP is 46% compared to 30% for ventilated patients who did not develop VAP. The art of choosing the best antibiotic combination that can cover the most common pathogen causing this fatal type of pneumonia is still a point of research.

Bacteriologically, the most common pathogen causing this fatal type of pneumonia is the Gram-negative microorganisms, especially pseudomonas aeruginosa and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus(MRSA). MRSA accounts for 10%–40% of cases of healthcare–associated (HCAP), HAP, and VAP.[5],[6],[7],[8],[9] In some centers, MRSA pneumonia occurs with equal frequency in HCAP as in HAP and more commonly than in VAP.[7],[8] A longitudinal study conducted on 1200 patients in US intensive care units showed that the proportion of MRSA isolates increased from 36% in 1992 to 64% in 2003;[8] however, rates may now be decreasing.[10],[11]

Pseudomonas aeruginosa reported to be resistant to the most common antibiotics used in ICU, while MRSA has special selection to the devitalized lung tissue, especially the traumatized contused lung which is considered the perfect media for these two pathogens by exudative phase of inflammation due to chest trauma filling the alveoli with debris and necrotic proteinaceous material all over the bronchioles. Moreover, the vasoconstrictor reflex occurs as a response to relative hypoxia in the traumatized area in the lung compromising its local immunity and making it vulnerable to this fatal type of pneumonia. Selection of the proper antibiotics is considered the cornerstone of management in those cases.[12]

Vancomycin enjoyed a long history of being the drug of choice against MRSA and Enterobacter. It inhibits bacterial cell wall synthesis by blocking glucopeptide polymerization through binding tightly to D-alanine portion of cell wall precursor. Linezolid uniquely and selectively inhibits bacterial protein synthesis by blocking the formation of a functional “70s initiation complex” which is considered an essential step for the bacterial translation process; but the most important two advantages of linezolid over vancomycin are its safety profile on the renal functions and its high tissue concentration, especially in the lung tissue as vancomycin is only 18% times serum level concentrated in lung tissue compared to 400% times serum level concentration of linezolid in lung tissue. These two unique advantages enable linezolid to be a better drug than vancomycin in treating tissue infection while vancomycin is considered the best in treating bloodstream infection (bacteremia or septicemia).[13],[14],[15],[16]

Clinically, the diagnosis of VAP can be done by the application of a modified clinical-pulmonary infection score (CPIS) [Table 1].[3],[4],[5],[6],[7],[8] The rapid control of both the systemic and local signs of VAP is considered the cornerstone in the management of VAP even before complete bacteriological cure as rapid weaning from the ventilator depends on controlling both local and systemic signs of VAP. All strategies of chemotherapy combinations try to reach this control as soon as possible to shorten the duration of mechanical ventilation and stop septic inflammation which delays the healing of the contused lung.[17],[18],[19]
Table 1: Modified clinical-pulmonary infection score (clinical pulmonary infection score)

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The use of tazocin/linezolid had significant statistical rapid control on both local and systemic signs of VAP. This combination shortened the duration of mechanical ventilation compared to tazocin/vancomycin. This effect could be attributed to the high concentration of linezolid in the lung tissue compared to vancomycin which has higher blood level than linezolid.[20],[21],[22]

Aim of work

The aim of the work is to evaluate and compare the effect of using tazocin (piperacillin + tazobactam)/vancomycin versus the use of tazocin (piperacillin + tazobactam)/linezolid in the treatment of VAP and weaning from the ventilator in traumatized contused lungs in patients with severe chest trauma complicated with VAP.


  Patients and Methods Top


This was a prospective double-blind study conducted on 200 patients admitted to King Abdul-Aziz Specialized Hospital, Taif, KSA between March 2013 and December 2016 in surgical ICU. All patients were having severe chest trauma, contused lungs either with or without severe head trauma.

King Abdul-Aziz Specialized Hospital research and the ethical committee approved the project and written consent for all the patients was taken from the first degree relatives of the patients.

Inclusion criteria

  • Age group between 18 and 50 years
  • Computerized tomography (CT) chest is considered the only diagnostic tool for lung contusion
  • Intubated and ventilated patients due to respiratory failure from severe lung contusion were enrolled in the study once admitted from the ER and all of them evaluated by the parameter of CPIS every 5 days for 15 days
  • Respiratory failure was diagnosed by arterial blood gases (ABG) with the partial pressure of oxygen ≤60 mmHg and/or partial pressure of carbon dioxide ≥60 mmHg
  • Any patient with Glasgow Coma Scale <8 from severe head trauma was intubated and included in our study only if he had severe lung contusion diagnosed by CT chest.


All patients enrolled in this study in both groups were diagnosed first as having lung contusion by CT chest and evaluated after 5 days from intubation and mechanical ventilation for development of VAP by modified CPIS. Those who get a score of 6 or more were eligible to enter into our study.

Exclusion criteria

  • Age <18 years or >50 years
  • Any patient with renal impairment
  • Any patient with acquired or congenital immunodeficiency syndrome
  • Any patient with ischemic or congenital heart disease
  • Any patient receiving corticosteroid treatment
  • Pregnant or lactating females.


The routine survey was done to all patients according to our hospital policy in the form of:

  • Chest X-ray, abdominal ultrasound, and CT brain as a routine in our hospital policy
  • Full laboratory work (complete blood count [CBC], complete chemistry, and coagulation profile)
  • The Acute Physiology and Chronic Health Evaluation II score was done for all patients.


All patients were intubated in ER or in our surgical ICU, then put on full ventilatory support and were sedated with intravenous analgesia using fentanyl 50–100 μg/h and intravenous sedation using midazolam 5 mg/h until we achieve a Ramsay score of 2–3.

All the patients were randomly allocated into two groups (Group A and Group B). The randomization sequence was created using Excel 2007 (Microsoft, Redmond, WA, USA) with a 1:1 allocation using random block sizes of 2 and 4 by an independent doctor. In this way, sequence generation and type of randomization can be expressed at the same time. Each group included 100 patients.

Patients of Group A received tazocin 4.5 g IV every 6 h and vancomycin 1 g slowly IV every 12 h, while patients of Group B received tazocin 4.5 g IV every 6 h and linezolid 600 mg slowly IV every 12 h once the diagnosis of VAP established by CPIS.

  • The temperature was measured every 3 h for 2 weeks
  • ABG was done every 8 h for 2 weeks
  • CBC including white cell count was done daily and for 2 weeks
  • Complete renal functions daily (urea and creatinine serum level) for 2 weeks.


Any patient showing a rise in the creatinine level was recorded and excluded from the study.

  • Chest X-ray for all the patients was ordered after intubation and with the onset of ventilation and every 24 h for 2 weeks
  • All patients received anti-stress (Omeprazole 20 mg IV every 12 h)
  • Orogastric tubes were inserted to all patients and feeding was started within 24 h
  • Daily evaluation for conscious level and need for sedation and ventilation were done for all patients
  • Tracheobronchial lavage was obtained by bronchoscopy 2 times a week and sent for qualitative culture for 2 weeks
  • Blood culture was also taken 2 times per week for 2 weeks
  • The planned duration of the study is 2 weeks from diagnosis of VAP and starting the antibiotics, so any patients who failed to be weaned within this period were considered morbidity and recorded.


The five points of the bundle for VAP prevention were strictly applied to all patients in both Groups A and B:

  1. Elevation of the head of the bed 30° to 45°
  2. Daily evaluation for possible extubation
  3. The use of an endotracheal tube with subglottic secretion drainage
  4. Oral care with oral antiseptic
  5. Initiation of safe enteral nutrition, if possible, within 24–48 h from ICU admission, intubation, and mechanical ventilation.


Statistical analysis

Sample size calculation was conducted using Epi-save software to conduct a comparative study. The estimated sample size is made at an assumption of 95% confidence level and 80% power of the study. The primary outcome measure percentage of improvement in modified CPIS. The data were collected and entered into the personal computer. Statistical analysis was done using Statistical Package for Social Sciences (SPSS/version 20, Atlanta, Georgia, United state) software. The statistical tests used were as follows:

Number, percentage, arithmetic mean, and standard deviation. For categorized parameters, Chi-square test was used, while for two groups t-test was used for parametric data. The level of significance was considered 0.05.


  Results Top


The demographic data of both groups are shown in [Table 2].
Table 2: Demographic data of the studied patients' groups

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Two patients were excluded from Group A as they had rising creatinine level 5 days and 7 days from starting vancomycin, respectively.

After the 2 weeks (duration of the study): patients failed to be weaned from the ventilator were 15 patients from Group A compared to only five patients from Group B as shown in [Table 3] [Figure 1].
Table 3: Number and percentage of patients weaned from mechanical ventilation throughout the study

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Figure 1: Number and percentage of patients weaned and non-weaned from mechanical ventilation throughout the study

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[Figure 2] is comparing the percent of patients in the two groups who had either a score of 0, 1, or 2 according to nature of the tracheal secretion in CPIS throughout the study.
Figure 2: Tracheal secretion in the two studied groups

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[Figure 3] is comparing percent of patients in the two groups who had either a score of 0, 1, or 2 according to size of parenchymatous lung infiltrate on the chest X-ray in CPIS throughout the study.
Figure 3: Chest X-ray infiltrate in the two studied groups

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[Figure 4] is comparing percent of patients in the two groups who had either a score of 0, 1, or 2 according to degree of core temperature in CPIS throughout the study.
Figure 4: Degree of core temperature in the two studied groups

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[Figure 5] is comparing percent of patients in the two groups who had a score of either 0, 1, or 2 according to total leucocytic count in CPIS throughout the study.
Figure 5: Leucocytic counts/mm3 in the two studied groups

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[Figure 6] is comparing percent of patients in the two groups who had a score of either 0, 1, or 2 according to hypoxic index in CPIS throughout the study.
Figure 6: Hypoxic index (partial pressure of oxygen/fraction of inspired oxygen) in the two groups throughout the study

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[Figure 7] is comparing percent of patients in the two groups who had either a score of 0, 1, or 2 according to qualitative trachea-bronchial lavage culture in CPIS throughout the study.
Figure 7: Microbiology findings in the two groups throughout the study

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As regards the control of local signs of ventilator-associated pneumonia in the contused lung

Tracheal secretion

Scanty tracheal secretion significant in Group B compared to Group A during the duration of the study. At the end of the first 5 days, end of the second 5 days and end of the last 4 days.

The control of purulent tracheal secretion was significantly better in Group B compared to Group A all over the duration of the study.

Negative qualitative bacteriological culture from tracheal secretion was significantly better in Group B compared to Group A within the duration of the study. At the end of the first 5 days, end of the second 5 days and end of the last 4 days.

Chest X-ray

Disappearance of parenchymatous lung infiltrate in the chest X ray was significantly better in group B compared to group A within the duration of the study.

Hypoxic index partial pressure of oxygen/fraction of inspired oxygen

Number of patients having hypoxic index >240 (or no ARDS) is significantly higher in Group B compared to Group A all over the duration of the study.

As regards the control of systemic signs of ventilator-associated pneumonia in contused lung

Leukocytic count

Number of patients who had normal leukocytic count in Group B was significantly higher compared to Group A in all the duration of the study.

Temperature

Number of patients who had core temperature between 36.5°C and 38.4°C in Group B was significantly higher compared to Group A in all the duration of the study [Table 4] and [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7].
Table 4: Number and percentage of patients who had either a score of 0, 1 or 2 for all clinical pulmonary infection score parameters throughout the study

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  Discussion Top


The pharmacodynamics of Tazocin linzolid in Group B ensure excellent tissue penetration and maintaining high tissue level and thus explaining the rapid control of both local signs of parenchymatous lung inflammation which measured by scanty tracheal secretion significant in Group B compared to Group A during the duration of the study. At the end of the first 5 days, end of the second 5 days and end of the last 4 days with the control of purulent tracheal secretion in Group B compared to Group A allover the duration of the study, negative qualitative bacteriological culture from tracheal secretion in Group B compared to Group A within the duration of the study. At the end of the first 5 days, end of the second 5 days and end of the last 4 days this can also be explained by high tissue level of linezolid.

Disappearance of parenchymatous lung infiltrate in the chest X-ray with improvement of the hypoxic index in Group B compared to Group A within the duration of the study can also be explained by higher tissue level of linezolid over vancomycin in lung infection (400 times concentrated in lung tissue more than serum compared to only 18 times concentration of vancomycin in lung tissue more than serum).

As regards the control of systemic signs of ventilator-associated pneumonia in the contused lung

The number of patients who had normal leucocytic count in Group B with controlled core temperature was significantly higher compared to Group A in all the duration of the study could be explained by rapid control of tazocin linezolid to all local signs of lung inflammation and thus better and rapid control of the systemic signs of inflammation.

The results of our study are similar to the results of a multicenter trial done in 2012 in US involving 1184 patients with hospital-acquired MRSA pneumonia allocated blindly in two groups; the group that received linezolid showed better clinical success as regard SPO2, chest X-ray, lung compliance and blood gasses compared to those who received vancomycin.[23]

Another two double-blind studies done and published in American College of chest physicians in 2003 comparing the efficacy of linezolid over vancomycin in MRSA nosocomial pneumonia and concluded that linezolid treated patients showed better survival and clinical cure rates than vancomycin-treated patients yet still vancomycin enjoy the superiority in hitting blood septicemia than linezolid because of higher blood level of vancomycin than linezolid.[24]


  Conclusion Top


The use of tazocin/linezolid provided rapid response in the treatment of VAP and less morbidity by shortening the duration of ventilation than tazocin/vancomycin inpatients with traumatized contused lungs.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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