Research Article - Journal of Trauma and Critical Care (2017) Volume 1, Issue 2

Ventilator associated pneumonia in Egyptian critically ill preterm and full term neonates.

¹Faculty of Medicine, El-Gaish, Tanta Qism 2, Tanta, Gharbia Governorate, Egypt

²Faculty of Medicine, Benha University, Benha, Qalubiya Governorate, Arab Republic of Egypt, Egypt

*Corresponding Author:

Mohamed A.El-Gamasy
Faculty of Medicine
Tanta
Gharbia Governorate
Egypt
Tel: +201208136076
E-mail: mgamsy@gmail.com

Accepted Date: July 18, 2017

Citation: Awny MM, El-Gamasy MA, Elsadek AE, et al. Ventilator associated pneumonia in Egyptian critically ill preterm and full term neonates. J Trauma Crit Care. 2017;1(2):4-17

Abstract

Ventilator associated pneumonia in Egyptian critically ill preterm and full term neonates.

Keywords

Ventilator associated pneumonia, Preterm, Neonates

Introduction

Pneumonia is an important cause of neonatal infection and accounts for significant morbidity and mortality, especially in developing countries [1,2]. Neonatal pneumonia may be classified as early onset (within the first 3 days of life, mostly within 48 hours), or late onset (from 4 till 28 days of life). Congenital or intrauterine pneumonia which is a variant of early onset pneumonia either acquired by trans-placental spread or from aspiration of infected amniotic fluid after prolonged premature rupture of membranes (PROM) or during delivery [3]. Late onset pneumonia is nosocomial infection [4]. Pneumonia mortality risk is strongly dependent on birth weight and age of onset. Case fatality rates are much higher for intrauterine or early onset pneumonia than for late on set neonatal pneumonia [4,5] and higher among low birth weight newborns [6]. VAP occurs in patients receiving mechanical ventilation through an endotracheal or tracheostomy tube within 48 hours [7,8].

Difficulties in diagnosis of VAP have led to the development of many diagnostic techniques such as blood culture, bronchoalveolar lavage, protected specimen brush and quantitative endotracheal aspirates. The gold standard for diagnosis of VAP is lung biopsy; however it is an invasive procedure [7].

Risk factors for VAP include prematurity, very low birth weight, severe underlying disease, prolonged duration of mechanical ventilation, use of wide spectrum empirical antibiotics, prolonged hospital stay, inadequate pulmonary care, extensive use of invasive devices and procedures, and increased number of re-intubation [9].

Aim

To find out the prevalence, risk factors, causative microorganisms and outcome of VAP in preterm and full term neonates admitted to NICU of TUH and BUH in Egypt.

Materials

This prospective study was carried out after approval from Research Ethical Committee Centre of Tanta and Benha University Hospitals and obtaining an informed oral or written consents from parents of included neonates in NICU of the Pediatric Department of TUH and BUH as tertiary care teaching hospitals over a period of twenty four months from January 2015 to January 2017, on 150 neonates. Their ages ranged from 0 to 28 days. They were 76 males and 74 females. The studied patients were120 neonates who received MV for more than 48 hours. Patients were classified into two groups:

Group 1 (VAP in preterm neonates)

Included 60 preterm neonates, their weight ranged from 0.9 to 2.5 kg, gestational age <37 weeks. This group was sub classified into Group 1a (Early onset VAP in preterm neonates): included 30 preterm neonates who acquired VAP in the first 3 days of age and Group 1b (Late onset VAP in preterm neonates): included 30 preterm neonate who acquired VAP after the first 3 days of age.

Group 2 (VAP group in full term neonates)

Included 60 full term neonate, their weight ranged from 2.6 to 4.3 kg, gestational age ≥ 37 weeks. This group was then sub classified into two group Group 2a (Early onset VAP in full term neonates): included 30 full term neonates who were acquired VAP in the first 3 days of age and Group 2b (Late onset in full term neonates): included 30 full term neonate who acquired VAP after age of 3 days. Group 3 (Control group): Included 30 neonates of age ranged from 0 to 28 days, their weight ranged from 2.5 to 4 kg, gestational age from 38 to 42 weeks admitted to NICU due to various illness not received mechanical ventilation.

Inclusion criteria

All neonates on MV for more than 48 hours provided that they had no clinical, laboratory or radiological manifestations of pneumonia at the time of initiation of MV.

Exclusion criteria

Neonates who required MV for less than 48 hours, who had pneumonia at the time of initiation of MV, meconium aspiration syndrome (MAS), pulmonary edema or congenital anomalies of the lung.

Contraindications to NB-BAL sampling

High oxygenation requirement (FIO2 >0.85), pneumothorax, bradycardia (heart rate <80 beats/min), hypotension or thrombocytopenia (platelet count <30,000/mm³).

Centers for Disease Control and Prevention (CDC) has recommended the following criteria for diagnosis of VAP in neonates and infants under one year of age: Patients who are mechanically ventilated for more than or equal to 48 hours with worsening of gas exchange (O2 desaturations, pulse oximetry <94%, increased oxygen requirements or increased ventilator demand) and at least three of the following symptoms and signs: Temperature instability (Rectal temperature >38°C or <35.5°C), apnea, tachypnea, nasal flaring with retraction of chest wall, grunting, wheezing, rales, rhonchi, cough, bradycardia (<100 beats/min) or tachycardia (>170 beats/min), new onset of purulent sputum, change in character of sputum, increased respiratory secretions, increased suctioning requirements, leukopenia (<4,000 WBC/mm3), leukocytosis (>15,000 WBC/ mm3), left shift (>10% band), more than ten leucocytes in Gramstain of tracheal aspirate (in high power field), positive culture from endotracheal aspirate or radiologically new, persistent or progressive infiltrate [10].

Methods

Case selection method

As we selected neonates from 2 large university referral hospitals, we see very large numbers of neonates who met inclusion criteria but we intended to select only 120 neonates (40 for each group) to be included in our study who for proper comparison using statistical analysis.

All neonates in this study were subjected to

1. History taking (personal data, perinatal history, present history, and duration of hospital stay)and clinical examination (Gestational age estimation, Vital signs including temperature, heart rate, and respiratory rate, pulse oximetry and signs of respiratory distress).

2. Data collection about MV: Chronological age at start of MV, duration of MV, number of re-intubations, ventilator modes, settings including peak inspiratory pressure (PIP), positive end expiratory pressure (PEEP), fraction of inspired oxygen (FIO2), feeding on MV whether nasogastric tubal feeding NGT or total parenteral nutrition (TPN), insertion of umbilical vein catheter (UVC).

3. Investigations: This was done at the time of initiation of MV and repeated when VAP was suspected.

3a) Laboratory:

• Complete blood count (CBC) especially Total Leucocytic Count (T.L.C), Differential Leucocytic Count (D.L.C), band forms of white blood cells and immature to total leucocytic count).

• C-reactive protein (CRP).

• Arterial blood gases (ABG).

• Blood culture and sensitivity.

• Non- bronchoscopic broncho alveolar lavage (NB-BAL) culture and sensitivity.

Preparation for sampling for BAL culture:

1. If neonate was inter breathing or fighting on the ventilator, sedation was required.

2. Pre-oxygenation by increasing FIO2 just before procedure.

3. Positioning: Supine with the head turned 900 to the left to ensure that the suction catheter can advance down through trachea to enter the right main bronchus.

4. A complete clinical examination and chest radiograph were performed one hour after completion of sampling.

BAL sample collection:

For 3.5 mm endotracheal tube(ETT), 8F sized end hole suction catheter which was filled with sterile water and connected to a low pressure suction device (6F sized catheter can be used for 3 mm or smaller size ETT). The ETT was disconnected from ventilator circuit (VC) and 0.5-1 ml sterile water was directly injected in the tube via a sterile disposable syringe for lavage. The suction catheter was then advanced immediately into the ETT until 1cm beyond the tube tip, to suction back the sterile water from the lower airways. The obtained fluid was immediately sent to the clinical pathology and microbiology laboratory of TUH.

BAL examination:

1. Macroscopic examination: The appearance, volume, color, consistency and aspect.

2. Microscopic examination:

• The number of white blood cells was estimated.

• A film stained with Leishman stain was done to determine the predominant type of cells.

• Another film stained with Gram stain was done to determine the presence of organisms.

3. The specimen was then centrifuged and pellet was inoculated on:

• A blood agar plate (sheep RBCs 5-10%) incubated for 48 hours at 37°C under anaerobic conditions.

• Chocolate agar plate incubated for 48 hours at 37°C in CO2 enriched atmosphere.

• Mac Conkey agar plate incubated for 48 hours at 37°C under aerobic condition.

4. The species and strain of bacteria were identified and the most effective antibiotic drugs at inhibiting their growth were determined.

3b) Chest radiography (Plan X-ray anterposterior and lateral views): On admission and repeated as required.

Statistical Analysis

The collected data were tabulated and analyzed using SPSS version 20. Categorical data were presented as number and percentages while quantitative data were expressed as mean ± standard deviation and range. Chi square test (X2), Fisher's exact test (F) and Receiver Operating Characteristic (ROC) curve. The accepted level of significance in this work was stated at 0.05 [11]. P value >0.05 is non-significant (NS). P<0.05 is significant (S). P ≤ 0.001 is highly significant (HS).

Results

Table 1 summarized demographic and laboratory data of studied patients and controls. Table 2 compare between studied groups as regarding the need for resuscitation measures at birth. Table 3 compared between different studied groups as regarding diagnosis at admission. Table 4 compared between studied patients as regarding risk factor for VAP. There is significant increase in duration on mechanical ventilation in late full term when compared to early full term subgroups (p<0.05). Respiratory acidosis was the commonest finding in preterm group, while metabolic acidosis was the commonest finding in full term group (P<0.05). Mortality rate was higher in early onset VAP in preterm group (13.3%) than in other patient groups (6.7%). Table 5 summarized laboratory data of studied groups. There is significant decrease in I/T ratio in PT group than FT group than controls (P<0.05). Table 6 and Figure 1 compared between studied patients as regard causative organism according to blood culture. 75% of patients in studied groups showed negative blood culture. The commonest organism detected in blood culture in early onset VAP in preterm subgroups was E. coli and S. aureus (13.3%). Table 7 and Figure 2 compared between studied patients as regard sensitivity of blood culture to antibiotics showing that E. coli is most sensitive to Meropenam (75%), Pseudomonas to Meropenam also (100%), Klebsiella pneumonie to Amikacin, Meropenam and Levofloxacin (33.3%), Staphylococcus aureus to vancomycin (80%), Streptocoocus viridans is to azithromycin (100%). Table 8 and Figure 3 compared between studied patients regarding causative organism by BAL culture. The commonest organism detected in NB-BAL culture in early and late onset VAP in preterm subgroups was Klebsiella pneumonie (40%).

Table 1. Demographic and laboratory data of studied patients and controls.

Table 2. Comparison between studied groups as regarding the need for resuscitation measures at birth.

Table 3. Comparison between studied groups as regarding diagnosis at admission.

Table 4. Comparison between studied patients as regarding risk factor for VAP.

Table 5. Laboratory data of studied groups.

Table 6. Comparison between studied patients as regarding bacteriological results of blood culture (causative organism).

Table 7. Comparison between studied patients as regarding bacteriological results of blood culture (sensitivity to antibiotics).

Table 8. Comparison between studied patients as regarding bacteriological results of BAL culture (causative organism).

Figure 1: Distribution of causative organisms among studied patients according to blood culture results.

Figure 2: Distribution of causative organisms among studied patients according to BAL culture results.

Figure 3: Distributions of antibiotics sensitivity of causative organisms detected by BAL culture of the studied patients.

Table 9 and Figure 4 compared between studied patients as regard causative organism by BAL culture showing that E. coli is most sensitive to ciprofloxacin (42.9%), Pseudomonas to tazobactam (42.9%), Klebsiella pneumonie to gentamycin (45%), Staphylococcus aureus to vancomycin (57.1%), Enterobacter gergoviae to amikacin (42.9%) and gentamycin (42.9%), Streptocoocus viridans to azithromycin (100%) and Klebsiella ozaenae to gentamycin (100%). Tables 10 and 11 summarized relation of data of mechanical ventilation to causative organisms of VAP by BAL culture in studied preterm and full term group and Table 12 summarized adjusted odds ratio of the studied patients. There is no significant relation between number of reintubation, mechanical ventilator duration, modes or settings and causative organisms of VAP in studied preterm or full-term group (P>0.05). Table 13 and Figures 5 and 6 compared validity of BAL culture to that of blood culture for diagnosis of VAP in the studied patients groups and reported that NB-BAL culture in preterm studied group has higher sensitivity (75% vs. 46%) and specificity (71% vs. 57%) than blood culture and reported that NB-BAL culture in full-term studied group also has higher sensitivity (80% vs. 53%) and specificity (72% vs. 55%).

Figure 4: Distributions of antibiotics sensitivity of causative organisms detected by blood culture of the studied patients.

Figure 5: Receiver operating characteristics (ROC) curve of BAL and blood culture in the studied preterm group.

Figure 6: Receiver operating characteristics (ROC) curve of BAL and blood culture in the studied full term group.

Table 9. Comparison between studied patients as regarding bacteriological results of BAL culture (sensitivity to antibiotics).

Table 10. Relation of data of mechanical ventilation to causative organism of VAP (BAL culture) in studied preterm group.