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Advances in Medical Sciences 61 (2016) 90–95

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Advances in Medical Sciences


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Original Research Article

Device-associated pneumonia of very low birth weight infants in


Polish Neonatal Intensive Care Units
Jadwiga Wójkowska-Mach a,*, T. Allen Merritt b, Maria Borszewska-Kornacka c,
Joanna Domańska d, Ewa Gulczyńska e, Marek Nowiczewski e, Ewa Helwich f,
Agnieszka Kordek g, Dorota Pawlik h, Paweł Adamski i
a
Chair of Microbiology, Jagiellonian University Medical College, Krakow, Poland
b
Division of Neonatology, Loma Linda University Children’s Hospital, Loma Linda, CA, USA
c
Clinic of Neonatology and Intensive Neonatal Care, Warsaw Medical University, Warsaw, Poland
d
Institute of Theoretical and Applied Informatics of Polish Academy of Sciences, Gliwice, Poland
e
Clinic of Neonatology, Polish Mother’s Memorial Hospital-Research Institute, Lodz, Poland
f
Clinic of Neonatology and Intensive Neonatal Care, Institute of Mother and Child, Warsaw, Poland
g
Department of Neonatal Diseases, Pomeranian Medical University, Szczecin, Poland
h
Clinic of Neonatology, Jagiellonian University Medical College, Krakow, Poland
i
Institute of Nature Conservation, Polish Academy of Sciences, Krakow, Poland

A R T I C L E I N F O A B S T R A C T

Article history: Purpose: Late-Onset Pneumonia (LO-PNEU) is still the most important complication associated with the
Received 5 March 2015 hospitalization of infants with very low birth weight (<1501 g). The purpose of this paper is to
Accepted 10 September 2015 summarize the results of an ongoing surveillance program defining LO-PNEU as associated or not
Available online 26 September 2015
associated with respiratory support in the NICU and distribution of causative pathogens from the Polish
Neonatology Surveillance Network (PNSN).
Keywords: Materials and methods: Surveillance of infections was conducted in the years 2009–2011 at six Polish
Very low birth weight newborns
NICUs.
Pneumonia
Device-associated pneumonia
Results: The incidence was 3.1/1000 NICU patient days (pds). The mean gestational age and birth weight
Surveillance among infants with LO-PNEU were significantly lower. The VAP incidence was of 18.2/1000 NICU pds for
Non fermentative bacilli mechanically ventilated (MV) infants, while the rates for those receiving only CPAP were as low as
7.7/1000 NICU pds. MV significantly increased the risk of PNEU, but MV or CPAP for <10 days did not
increase the risk of LO-PNEU. Significantly associated with LO-PNEU was the use of central or peripheral
venous catheters and total parenteral nutrition for longer periods.
Microorganisms isolated in cases of LO-PNEU were Gram-positive cocci (53.5%) and Gram-negative
rods, with predominating E. coli. Non fermentative bacilli were significantly more frequent in cases of
VAP than in other cases.
Conclusions: Observed incidence rates associated with VAP and CPAP-PNEU, were higher than in other
national surveillance systems and expressing the feasibility of lowering the risk of LO-PNEU and
increasing patient safety. The incidence of pneumonia was found to be lower when using CPAP as
compared to using MV.
ß 2015 Medical University of Bialystok. Published by Elsevier Sp. z o.o. All rights reserved.

1. Introduction conditions in both term and preterm infants result in hypoxic


respiratory failure. Endotracheal intubation and mechanical venti-
Many premature infants require endotracheal intubation be- lation are associated with risks of respiratory tract colonization and
cause of respiratory distress syndrome or when other pulmonary infection, resulting in pneumonia. These latter cases may be
nosocomial, and may or may not be accompanied by a systemic
infection with positive blood cultures and changes in chest x-rays
interpreted as ‘‘pneumonia’’.
* Corresponding author at: Chair of Microbiology, Jagiellonian University Medical
These patient-related, or infection-control complications may
College, 18 Czysta Street, 31-121 Krakow, Poland. Tel.: +48 12 633 00 60;
fax: +48 12 423 39 24. result from altered host responses, especially in premature infants,
E-mail address: mbmach@cyf-kr.edu.pl (J. Wójkowska-Mach). and from a large bacterial ‘‘load’’ resulting in airway and lung

http://dx.doi.org/10.1016/j.advms.2015.09.002
1896-1126/ß 2015 Medical University of Bialystok. Published by Elsevier Sp. z o.o. All rights reserved.
J. Wójkowska-Mach et al. / Advances in Medical Sciences 61 (2016) 90–95 91

parenchyma infection [1]. The presence of an endotracheal tube 2.1. Description of the population
and the duration of mechanical ventilation have been associated
with the highest risk of ventilator associated pneumonia (VAP) This surveillance included 1695 newborns. Analyses of the
[2,3], and the intubation procedure may itself significantly increase influence of selected factors for the risk of PNEU were based on the
this risk [2]. In the United States, the National Healthcare Safety group surviving three or more days. The intubation utilization ratio
Network (NHSN) implemented in 2002 a specific definition to be was 0.25 for MV and 0.18 for CPAP (measures the present of total
used for the surveillance of all healthcare-associated pneumonias, patients days in which a high-risk device – MV or CPAP – was used,
including (but not limited to) ventilator associated pneumonia calculated by dividing the number of ventilator days by the
[4]. In Poland, similar surveillance of infections occurring in number of patient days). Tracheo-bronchial secretions, nasopha-
different types of intensive care units has been systematically ryngeal aspirates and blood cultures were collected for culture and
collected over the last several years [5,6]; however, there have assessment for infection in infants depending upon their mode of
been no reports on the epidemiology of respiratory infections in respiratory support. Microbial (bacteria and fungi) species
Polish Neonatal Intensive Care Units (NICUs) in order to establish identification was determined in laboratories associated with
effective or achievable infection control measures designed to each NICU.
prevent or minimize VAP. The purpose of this paper is to For the evaluation of the differences between the means for the
summarize the results of an ongoing surveillance program defining infants under surveillance (those with VAP and CPAP PNEU) versus
Late-Onset Pneumonia (LO-PNEU) associated with respiratory infants with early-onset symptoms, a one-way analysis of variance
support in the NICU and to associate these findings with (ANOVA) with the least significant difference (LSD) test and the
established risk factors for the identification and distribution of Tukey test were applied. A chi-square test for independence was
causative pathogens from the Polish Neonatology Surveillance used for the assessment of the frequency of infections in the infant
Network (PNSN). One of the purposes of this surveillance program groups. A Generalized Linear Model was applied to assess the
was to have uniform definitions, specimen acquisition, and significance of differences between positive cultures for coagulase-
culturing techniques for uniform infection surveillance so that negative staphylococci, or Enterobacteriaceae and/or other
VAP could be systematically reported. microorganisms and birth weight, gestational age, length of
hospitalization prior to the onset of initial symptoms and device
use for respiratory support. The statistical analysis based on
2. Materials and methods comparison of the frequencies of pneumonia with different
etiology between patients with/without MV or CPAP. Analyses
An Electronic database created as the result of continuous were conducted with Parsons’ chi square test or likelihood ratio –
prospective targeted surveillance of infections was used in the when the data structure did not fulfill the demands of the Parsons
study. Between 1 January 2009 and 31 December 2011, six Polish chi square. Analysis of the join impact of devices was done with
NICUs participated in the Polish Neonatology Surveillance Generalized Linear Model technique. Due to dychotomic character
Network (PNSN) to ascertain continuous prospective guided of both – dependent and independent variable model was
surveillance of respiratory (and other) infections among infants conducted for binominal distribution of effect and logit linked
receiving respiratory support. The PNSN is a prospective national function. All analysis were provided using the open source library
surveillance system for the most relevant infections in very low SciPy and with SAS JMP1 9.03 SAS; the assumed significance level
birth weight infants (VLBW, birth weight < 1500 g) in Poland. was p < 0.05.
Details of the following variables were collected for all VLBW Polish NICU data (regarding central venous catheterization,
newborns: birth weight and gestational age, gender, multiple intubation and CPAP) were compared with those of the German
pregnancy, type of delivery and information of the situation in time NeoKISS (German Krankenhausinfektionen Surveillance System)
of delivery, for example chorioamnionitis, general status of [8], which is a comprehensive surveillance of infections in German
newborns by Apgar score: at 1 and 5 min and Critical Risk Index NICUs and is generally comparable to the Polish data.
for Babies (CRIB) and others. The PNSN recorded severe infections,
including necrotizing enterocolitis observed at the time of 3. Results
hospitalization: from admission to discharge, transfer or death.
Participation in PNSN is voluntary and confidential. Utilization of There were 287 episodes of LO-PNEU diagnosed in Polish NICUs,
data collected in PNSN for the scientific purpose was approved by with an incidence of 3.1/1000 NICU pds. The most frequently
the Bioethics Committee of Jagiellonian University Medical College observed symptoms of PNEU were: worsening of gas exchange
– no. KBET/221/B/2011. All data entered into the electronic (96%), new radiographic findings of progressive infiltrates in one or
database and analyzed during the preparation of this article were both lungs (79%) and a documented increase in pulmonary
previously anonymized and de-identified. Those data were secretions with an increased need for suctioning (76%). An
obtained under routine diagnostic procedures performed during elevated C-reactive protein was found in 85.4% of the infants
patients’ hospitalization. According to Polish law, the use of the identified as having pneumonia. Demographic data are presented
data for scientific purpose does not demand patients’ agreement or in Table 1. The mean gestational age and birth weight among
even information that data are collected in the anonymized infants with LO-PNEU were significantly lower; however, PROM,
database. cesarean section and gestations with twins or triplets did not
All cases of Late-Onset Pneumonia (LO-PNEU) were registered influence the risk of PNEU. Females were less likely to develop
in reference to the time of symptom onset and the form(s) of LO-PNEU (odds ratio OR 0.6464, 95% confidence interval CI 0.4943–
respiratory support being provided to the infant. ‘‘Pneumonia’’ 0.8453) than males. The initiation of trophic feeding was an
cases in these NICUs were defined according to Gastmeier et al. [7] independent factor in the reduced risk of LO-PNEU (OR 0.6406,
as neonates with very low birth weight (VLBW) when they had 95%CI 0.4871–0.8425).
signs of pneumonia diagnosed >72 h after birth [7]. The Apgar scores at 1 min after birth were statistically lower
Ventilator associated PNEU (VAP) and Continuous Positive (0–4) in the group of infants with LO-PNEU (OR 1.9474, 95%CI
Airway Pressure (CPAP) associated PNEU (CPAP-PNEU) was 1.4727–2.5751). Similarly, the 5 min Apgar scores were lower
defined as PNEU with mechanical ventilation (MV) or CPAP use (scores <7) (OR 3.6263, 95%CI 2.532–5.1935) among infants
in the 48 h preceding the onset of the infection [7]. developing LO-PNEU. CRIB scores elevated from 5 to 15 indicating
92 J. Wójkowska-Mach et al. / Advances in Medical Sciences 61 (2016) 90–95

Table 1 Comparing the relationship between microbial etiology and


Characteristics of newborns with symptoms of LO-PNEU and without, who survived
type (or lack) of ventilator support in infants (MV vs. CPAP vs. non
to the third day and/or later.
MV or CPAP) turned out, that non fermentative bacilli Acinetobacter
Number of patients Average/95%CI p-value baumannii and Pseudomonas aeruginosa were significantly more
Newborns without Newborns with frequent in the case of VAP (chi square = 6.042, p = 0.0140), and
PNEU [N = 946] PNEU [N = 287] less frequently in patients without ventilator support, (G2 = 7.232;
Gestational age [week] 29 (29.1;29.4) 27 (26;27) <0.001 p = 0.0072), similarly to infections with CNS etiology.
Birth weight [g] 1113 (1088;1138) 867 (841;893) <0.001
Percentage of population [No./%] 4. Discussion
Female gender 481 50.8 115 40.1 <0.001
Cesarean section 736 77.8 212 73.9 –
Single birth 714 75.5 228 79.4 – Our results describing late-onset infections are based on data
Trophic feeding 434 45.9 101 35.2 <0.001 gathered by the PNSN program of infection control in neonatal
CRIB* units. In Poland, fewer than 5000 VLBW infants are born each year,
0–4 258 27.3 64 22.3 0.02 i.e., 0.9% of all live births [9]. Our previous reports on the study
5–10 68 7.2 61 21.3 <0.001
population were focused on early infections [10].
11–15 18 1.9 16 5.6 <0.001
15–22 2 0.2 1 0.3 – A significant drawback of the presented study is the use of
Apgar (1 min) infection definitions according to ones adopted for Neo-KISS. As a
0–4 234 24.7 112 39.0 <0.001 result, the presented results cannot be directly compared to data
5–7 486 51.4 161 56.1 –
from the NHSN program (before 2006 the system was called NNIS),
8–10 226 23.9 14 4.9 <0.001
Apgar (5 min) the largest database of knowledge on infections. This study permits
0–4 138 14.6 52 18.1 0.04 governmental and public reporting of the performance measure-
5–7 458 48.4 195 67.6 <0.001 ment of participating NICUs [11–14]. The choice and uniform
8–10 350 37.0 40 13.9 <0.001 application of relevant definitions remain a challenge, possibly
*
Clinical Risk Index for Babies. contributing to difficulties in including pneumonia in infection
surveillance for neonates.
A significant problem that may restrict effective surveillance
programs is the unique clinical picture of disease among extremely
more severe illness, were more frequently observed among infants small and immature infants that complicates the application of
with LO-PNEU (OR 3.6667, 95%CI 2.6033–5.1645). Infants with uniform definitions of ‘‘infection’’. Some of the symptoms of
symptoms of LO-PNEU developed more episodes of necrotizing pneumonia, such as worsening gas exchange, intercostal retrac-
enterocolitis (p < 0.0001, OR 1.7864, 95%CI 1.1172–2.8563). The tions, or respiratory acidosis, constitute important clinical
fatality case rate (6%), however, was not increased among infants symptoms that are characteristic of respiratory distress syndrome.
with LO-PNEU. In addition, the interpretation of the results of imaging examina-
The incidence of LO-PNEU was higher among infants with birth tions or analytical tests in VLBW infants is often problematic
weights <750 g (81.6%), while it was 56.8% among those with birth [14]. A significant challenge in the recognition of ventilator
weights between 750 and 999 g. The VAP rates of 35.4% associated pneumonia and comparisons among institutions has
represented an incidence of 18.2 episodes/1000 NICU pds for been the lack of uniform definitions, the characterization of clinical
mechanically ventilated infants, while the rates for those receiving presentation and consistent laboratory analysis including micro-
only CPAP were as low as 8.8%, i.e. 7.7/1000 NICU pds. Mechanical biologic identification of the number of colony-forming units of a
ventilation (MV) significantly increased the risk of PNEU (OR specific pathogen. Infants on mechanical ventilation, and especial-
6.0262, 95%CI 4.309-8.4277) and the use of MV for >17 days ly those of very low birth weight, are critically ill, frequently suffer
increased the risk of VAP to 9.6% (OR 18.4726, 95%CI 12.714– from complex acute illness complicated by multiple comorbidities,
26.8395). There was also an increased risk of PNEU among infants and may require extraordinary life-saving measures. More
receiving CPAP for more than 17 days (OR 10.7073, 95%CI 7.3244– recently, the shift in the focus on healthcare associated infection
15.6527). Noteworthy, was the observation that mechanical surveillance from Ventilator Associated Pneumonia to Ventilator
ventilation or CPAP for <10 days did not increase the risk of Associated Complications will require a substantial amount of
PNEU. The use of central venous catheters or peripheral venous clinical education and potentially a shift in how prevention
catheters for longer periods (e.g. >10 days) was significantly strategies are conceived and implemented. In 2013, NHSN
associated with LO-PNEU. The occurrence of LO-PNEU significantly published new guidelines for the surveillance for ventilator-
increased the need for the prolonged use of total parenteral associated pneumonia in adults and children (including infants <1
nutrition (Table 2). year old) and threshold values for cultured specimens used in the
diagnosis of pneumonia. Because substantial efforts are being
3.1. Microbial species isolated from the respiratory tract and blood made to reduce ventilator associated pneumonia, globally
samples of LO-PNEU cases standardized accepted definitions are critical to place both
historical reports of VAP over the last decade and to measure
Cultures to determine the bacterial or yeast etiology of how specific preventive strategies may be implemented at
pneumonia were performed in 72% of cases. Gram-positive cocci multiple sites to reduce these healthcare associated infections.
represented 53.5% of the isolated pathogens and were isolated This broader concept of ventilator associated complications
from more than 50.0% of devices associated with PNEU cases emphasizes a ‘‘bundle’’ of interventions that may reduce both
(either MV or CPAP). Coagulase-negative staphylococci (CNS) were infectious and non-infectious complications associated with
isolated from 40.1% and Staphylococcus aureus from 8.2% of mechanical ventilation in infants.
pneumonia cases. Gram-negative rods with predominating Klebsi- Analysis of LO-PNEU epidemiology in Polish NICUs has shown
ella spp. and E. coli were isolated from 46.5% of all isolates. 4.3% of that – like in case of early-onset infections in Polish NICUs [10] –
all PNEU was caused by yeast-like fungi (Table 3). No significant the incidence rate in NICUs was higher than in some other national
relationship was found between the microbial etiology of LO-PNEU programs, including the German Neo-KISS [15]. In the USA, the
and birth weight, gestational age, or specific device use. median incidence rate was less than 2/1000 MVdays – on a level
J. Wójkowska-Mach et al. / Advances in Medical Sciences 61 (2016) 90–95 93

Table 2
Procedures applied and antibiotic consumption in newborns with symptoms of LO-PNEU compared to those without LO-PNEU, who survived to the third day and/or later.

Length of procedure [days] Average/95%CI p-value

Newborns without PNEU Newborns with PNEU [N = 287]


[N = 946]

CVC 15 (14; 16) 39 (35; 43) <0.001


PVC 10 (9; 10) 22 (19; 25) <0.001
Mechanical ventilation 9 (8; 10) 38 (33; 44) <0.001
CPAP 9 (8; 9) 16 (14; 17) <0.001
Total parenteral nutrition 14 (14; 15) 34 (30; 37) <0.001
Antimicrobial medicines 12 (11; 13) 41 (37; 45) <0.001

Percentage of population [No/%]


CVC* total use
CVC – newborns [No.] 748 79.1 251 87.5 <0.001
1–10 days 265 35.4 23 9.2 <0.001
11–16 days 161 21.5 26 10.4 –
17–23 days 123 16.4 37 14.7 <0.001
<23 days 114 15.2 138 55.0 <0.001
PVC* total use
PVC – newborns [No.] 506 53.5 223 77.7 <0.001
1–10 days 312 61.7 89 39.9 –
11–16 days 76 15.0 29 13.0 <0.001
17–23 days 28 5.5 23 10.3 <0.001
<23 days 19 3.8 69 30.9 <0.001
TPN* total use
TPN – newborns [No.] 816 86.3 267 93.0 <0.001
1–10 days 322 39.5 32 12.0 <0.001
11–16 days 189 23.2 37 13.9 –
17–23 days 104 12.7 40 15.0 0.008
<23 days 95 11.6 135 50.6 <0.001
Antibiotic treatment * total use
Antimicrobial drugs – newborns [No.] 811 85.7 272 94.8 <0.001
1–10 days 435 53.6 17 6.3 <0.001
11–16 days 123 15.2 20 7.4 <0.001
17–23 days 66 8.1 55 20.2 <0.001
<23 days 76 9.4 158 58.1 <0.001
*
MV applied before the onset of symptoms
MV – newborns [No.] 428 45.2 239 83.3 <0.001
1–10 days 284 66.4 55 23.0 <0.001
11–16 days 47 11.0 29 12.1 <0.001
17–23 days 19 4.4 23 9.6 <0.001
<23 days 28 6.5 118 49.4 <0.001
CPAP* applied before the onset of symptoms
CPAP – newborns [No] 604 63.8 241 84.0 <0.001
1–10 days 388 64.2 80 33.2 <0.001
11–16 days 47 7.8 37 15.4 0.004
17–23 days 38 6.3 46 19.1 <0.001
<23 days 19 3.1 57 23.7 <0.001

CPAP: Continuous Positive Airway Pressure; CVC: central venous catheter; MV: mechanical ventilation; PVC: peripheral venous catheter; TPN: total parenteral nutrition.
*
Entered for the procedure.

Table 3
Pathogens (bacteria) identified in case of LO-PNEU in VLBW infants (2009–2011).

Number/percentage Ranking

VAP-PNEU CPAP-PNEU Other LO-PNEU* Total


[N = 184] [N = 42] [N = 55]

Gram-positive cocci 104 53.6 24 52.2 23 54.8 151 53.5


CNS 78 40.2 17 37.0 18 42.9 113 40.1 1
Staphylococcus aureus 14 7.2 6 13.0 3 7.1 23 8.2 4
Enterococcus spp./Streptococcus spp 12 6.2 1 2.2 2 4.8 15 5.3 6

Gram-negative rods 90 46.4 22 47.8 19 45.2 131 46.5


Escherichia coli 27 13.9 8 17.4 8 19.0 43 15.2 3
Klebsiella spp. 34 17.5 9 19.6 6 14.3 49 17.4 2
Enterobacter spp. 13 6.7 4 8.7 5 11.9 22 7.8 5
Other Enterobacteriaceae 1 0.5 0 0.0 0 0.0 1 0.4 10
Acinetobacter baumanii 2 1.0 1 2.2 0 0.0 3 1.1 9
Pseudomonas aeruginosa 13 6.7 0 0.0 0 0.0 13 4.6 7

Total 194 100.0 46 100.0 42 100.0 282 100.0


Mixed culture** 45 7 9 61

CNS: coagulase-negative staphylococci; VAP: Ventilator-Associated Pneumonia.


*
Other LO-PNEU: cases of LO-PNEU in newborns who have not used MV or CPAP.
**
Percentage of mixed etiology (mixed cultures) from all microbiologically confirmed cases.
94 J. Wójkowska-Mach et al. / Advances in Medical Sciences 61 (2016) 90–95

closely resembling the ventilation utilization used in Polish NICUs reduce the use (or early completion) of an endotracheal tube for
[16]. These data indicate that surveillance of the incidence of mechanical ventilation or the preferred use of CPAP by Polish
pneumonia in Polish NICUs remains a serious problem. Unfortu- NICUs. Additionally, these recommendations should state that
nately, experience drawn from the Neo-KISS program shows that it non-invasive (passive) ventilation (such as CPAP or nasal ventila-
is not easy to significantly decrease the risk of VAP incidence: after tion) should be a preferred ventilator strategy in the NICU.
three years of surveillance, this program did not show any
significant decrease of the incidence rate (relative risk RR 0.99) Acknowledgments
[15]. This is very different from the situation in adult ICUs, where
the use of care bundles and proper hygiene standards allows for the We would like to especially thank the staff in the NICUs for their
possibility of significantly decreasing VAP risk [17]. In neonate ICU help and interest in the study. Special thanks for participating in
wards, some extra elements are required, e.g. Cordero reported a the design of the study are due to Prof. Janusz Gadzinowski and
decrease of VAP-related morbidity when a closed suction system is Prof. Jerzy Szczapa from Department of Neonatology, Poznan
used [18]. The problem is highly significant as VAP doubles the University of Medical School; for Prof. Piotr B. Heczko from Chair of
hospitalization time in neonate ICUs, increases the risk of infant Microbiology, Jagiellonian University Medical College, Krakow.
death [19] and utilization of central venous catheter (CVC),
peripheral intravenous catheter (PVC) and others.
The situation was similar in case of CPAP-PNEU incidence, Conflict of interests
which was lower than VAP incidence, but still higher, about 50% in
Poland, than in Germany. Unfortunately, there are no data on the The authors declare no conflict of interests.
risk of infants on CPAP developing pneumonia in other national
programs; however, Neo-KISS found that limiting this risk is also
Financial disclosure
very difficult. In Neo-KISS, the CPAP-PNEU incidence decreased (RR
0.42); however, this value was not significant [15]. But, on the
This study was supported by a grant from the Ministry of
other hand, in Germany CPAP utilization was two times higher
Science and Higher Education (DEC-2012/05/B/NZ7/02880).
than among Polish NICUs [15]. CPAP does significantly decrease the
need to use mechanical ventilation and decreases the risk of
pneumonia, insertion of needles into blood vessels, prolonged References
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