Journal of Infection and Public Health 10 (2017) 740–744

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Journal of Infection and Public Health

journal homepage: http://www.elsevier.com/locate/jiph

Distribution and antibiotic susceptibility of pathogens isolated from

adults with hospital-acquired and ventilator-associated pneumonia in
intensive care unit
Zorana M. Djordjevic a , Marko M. Folic b,∗ , Slobodan M. Jankovic b
a
Department to Control Hospital Infections, Clinical Centre Kragujevac, Kragujevac, Serbia
b
Clinical Pharmacology Department, Clinical Centre Kragujevac and Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia

a r t i c l e i n f o a b s t r a c t

Article history: Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the most common
Received 4 August 2016 hospital infections with the highest prevalence in intensive care units (ICU). The aim of this study was to
Received in revised form 6 October 2016 investigate prevalence of bacterial pathogens isolated from ICU patients with HAP/VAP and reveal their
Accepted 18 November 2016
susceptibility rates in order to establish a basis for empirical antibiotic therapy. Prospective cohort study
was conducted in central ICU of Clinical Centre Kragujevac, Serbia, from January 2009 to December 2015,
Keywords:
enrolling 620 patients with documented HAP (38.2%) or VAP (61.8%).
Hospital-acquired pneumonia
Gram-negative agents were isolated in 95.2%. Generally, the most common pathogens were Acineto-
Ventilator-associated pneumonia
Microbiology
bacter spp. and Pseudomonas aeruginosa, accounting for over 60% of isolates. The isolates of Acinetobacter
Resistance rate spp. in HAP and VAP had low susceptibility to the 3rd generation cephalosporins, aminoglycosides, fluo-
roquinolones (0–10%). The rate of susceptibility to piperacillin-tazobactam was below 15%, whereas for
carbapenems and 4th generation cephalosporins it was about 15–20%. Isolates of P. aeruginosa from HAP
and VAP showed low susceptibility to ciprofloxacin and gentamicin (below 10%), followed by amikacin
(25%), while the rate of susceptibility to carbapenems and 4th generation cephalosporin was 30–35%.
Furthermore, 86% of isolates of P. aeruginosa non-susceptible to carbapenems were also non-susceptible
to ciprofloxacin. The highest level of susceptibility from both groups was retained toward piperacilin-
tazobactam. In ICU within our settings, with predominance and high resistance rates of Gram-negative
pathogens, patients with HAP or VAP should be initially treated with combination of carbapenem or
piperacillin-tazobactam with an anti-pseudomonal fluoroquinolone or aminoglycoside. Colistin should
be used instead if Acinetobacter spp. is suspected. Vancomycin, teicoplanin or linezolide should be added
only in patients with risk factors for MRSA infections.
© 2017 The Authors. Published by Elsevier Limited. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction
Hospital-acquired pneumonia (HAP) and ventilator-associated
pneumonia (VAP) are the most common infections acquired in the
hospital with the highest prevalence in intensive care units (ICUs)
[1,2]. Depending on the case definition and study population inci-
dence of HAP is usually between 5 and 15 cases per 1000 hospital
admissions but incidence of VAP in patents on mechanical ventila-
tion is 6–20 fold greater [3–5].
These infections negatively impact important patient outcomes
and the health-care system because HAP and VAP significantly
∗ Corresponding author at: Faculty of Medical Sciences, University of Kragujevac,
Svetozara Markovica 69, 34000 Kragujevac, Serbia.
E-mail address: markof@medf.kg.ac.rs (M.M. Folic).
prolong treatment, escalate health care costs and are leading
cause of death attributed to hospital infections [6–8]. Physicians
everywhere struggle to control these infections, but with varying
success, despite wide-range of preventive measures and advances
in antimicrobial therapy. Another problem is insufficiently precise
definition of HAP and VAP in current guidelines (in 2016 guidelines
it was stated that no “gold standard” for the diagnosis of HAP or VAP
exists) [9], and clinicians are left without clear recommendations
regarding treatment decisions which leads to variation in antibiotic
use and potentially inappropriate use, resulting with worsening of
resistance issues.
HAP/VAP are caused by an imbalance between normal host
defenses and the ability of microorganisms to colonize and then
invade the lower respiratory tract. Although a wide spectrum
of bacterial pathogens can cause HAP/VAP the most frequent
causative agents are aerobic Gram-negative bacilli, especially Pseu-

http://dx.doi.org/10.1016/j.jiph.2016.11.016
1876-0341/© 2017 The Authors. Published by Elsevier Limited. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-
nd/4.0/).
 Z.M. Djordjevic et al. / Journal of Infection and Public Health 10 (2017) 740–744
domonas aeruginosa (P. aeruginosa), Acinetobacter spp ., Klebsiella
pneumoniae, Escherichia coli as well as Gram-positive cocci like
Staphylococcus aureus [10,11]. Bacteria which cause HAP/VAP are
often resistant to various antibiotics, but exact susceptibility pro-
file depends on hospital or ICU, patient population and previous
exposure to antibiotics. It is not static, but changes over time.
Many infections are polymicrobial and caused by multi-drug resis-
tant (MDR) pathogens. Since early initiation of appropriate empiric
antibiotic therapy is of vital importance for the patient, good knowl-
edge of local prevalence of pathogens and their drug susceptibility
patterns is essential. In some developing countries, the etiologic
agents of HAP/VAP and their susceptibility to antibiotics are not
systematically followed, making choice of empiric therapy difficult.
The aim of this study was to investigate prevalence of bacte-
rial pathogens isolated from patients with HAP/VAP in an ICU and
reveal their susceptibility rates in order to establish a basis for
empirical antibiotic therapy.
Methods
Study design and setting
We conducted a prospective cohort study in central ICU of Clin-
ical Centre Kragujevac, Kragujevac, Serbia from January 2009 to
December 2015. This Medical-Surgical ICU has 18 beds and annu-
ally about 850 patients are treated. The study was approved by the
Ethics Committee of Clinical Centre Kragujevac.
The patients
The study included patients older than 18 years with HAP/VAP
according to standard definition established by American Thoracic
Society (ATS) and Infectious Diseases Society of America (IDSA) Guide-
lines from 2005 [4] and updated in 2016 [11]. The patients with
isolation of causative agents within the first 48 h from admission
to hospital were excluded. Only the first isolate from each patient
was taken into account. Every patient was evaluated by the inde-
pendent expert group composed of infectious diseases specialist,
epidemiologist, specialist of intensive medicine and clinical phar-
macologist. The patients were followed to the final outcome, either
cure and discharge from the hospital or to the death.
Definition of pneumonia
Pneumonia was defined as the presence of new lung infiltrate
plus clinical evidence that the infiltrate is of an infectious origin,
including new onset of fever, purulent sputum, leukocytosis, and
decline in oxygenation. HAP is defined as a pneumonia which was
not present at the time of hospital admission and occurring 48 h or
more after the admission. HAP is also called “episode of pneumonia
not associated with mechanical ventilation”. VAP is defined as a
pneumonia occurring >48 h after endotracheal intubation [4]. The
patients which require intubation after developing severe HAP are
treated like patients with VAP.
Thus, HAP and VAP belong to 2 mutually exclusive groups. Diag-
nosing HAP/VAP requires high clinical suspicion combined with
bedside examination, radiographic studies, and microbiologic anal-
ysis.
Microbiological analysis
Bacteriological evidence of pulmonary infection was sought
in accordance to the guidelines. Clinically significant values for
quantitative culture were considered ≥104 colony forming units
(cfu)/ml for bronchoalveolar lavage (BAL), 103 –104 cfu/ml for mini
BAL, ≥105 cfu/ml for undiluted tracheal secretions and ≥105 cfu/ml
741
for sputum [12]. Growth below the threshold concentration was
assumed to be caused by colonization or contamination.
Isolation and identification of causative agents of HAP/VAP was
performed in the hospital microbiology laboratory, using conven-
tional biochemical methods [13]. The Antimicrobial susceptibility
test was made by disk-diffusion method on Mueller-Hinton Agar
(Biomerieux, France), by measuring the diameter of the zones of
inhibition. The tested isolates were classified as susceptible or resis-
tant (including intermediate) strains in accordance with guidelines
of The Clinical and Laboratory Standards Institute (CLSI)[14].
Susceptibility to the following antibiotics was analyzed:
amoxicillin + clavulanic acid (30 ␮g/mL), piperacillin-tazobactam
(110 ␮g/mL), ceftriaxone (30 ␮g/mL), ceftazidime (30 ␮g/mL),
cefepime (30 ␮g/mL), imipenem (10 ␮g/mL), meropenem
(10 ␮g/mL), gentamicin (10 ␮g/mL), amikacin (30 ␮g/mL) and
ciprofloxacin (5 ␮g/mL). MDR was defined as acquired non-
susceptibility to at least one agent in three or more antimicrobial
categories, by criteria proposed Magiorakos et al. [15].
Statistical analysis
The collected data were described by measures of central ten-
dency (mean, median) and variability (standard deviation) if their
nature was continuous, and by percentages, if the variables are cat-
egorical. Difference in values of a categorical variable among the
study groups was tested for significance by Chi-square test (e.g. dif-
ference in resistance rates of isolates). The hypotheses were tested
at 0.05 level of statistical significance. All calculations were per-
formed using the statistical software SPSS version 18 for Windows
(IBM SPSS, Inc, Chicago, Illinois, USA).
Results
In the observed period 620 patients admitted to the ICU devel-
oped HAP/VAP according to pre-defined criteria. HAP accounted
for 38.2% and VAP for 61.8% patients. The rate of HAP and
VAP was 10.3 cases per 100 patient-days. Mean patient age
was 59.65 ± 16.02 years (range 19–91) and 69.0% of the patients
(n = 428) were males.
In the majority of patients infection was caused by single
pathogen (n = 354; 56.9%), whereas in other patients it was caused
by two or three. Frequency of pathogens isolated from patients with
HAP and VAP is shown in Table 1. From the total of 983 positive
microbiological cultures Gram-negative agents were isolated in
95.2%. Generally the most common pathogens were Acinetobacter
spp. and P. aeruginosa accounting for over 60% of isolates.
A statistically significant difference in the frequency of HAP and
VAP isolates was found only for the S. aureus which was more fre-
quent in the HAP group (p < 0.001) (the data not shown).
The results of susceptibility testing for the seven Gram-negative
bacteria that most frequently caused HAP are shown in Table 2
and for causative agents of VAP in Table 3. According to these
results, the isolates of Acinetobacter spp. in both groups were
poorly susceptible to the third generation cephalosporins, amino-
glycosides and fluoroquinolones (0–10%). The susceptibility rate
to piperacillin-tazobactam was below15% whereas for carbapen-
ems and 4th generation cephalosporin (cefepime) was somewhat
higher (15–20%). Most isolates of Acinetobacter spp. from patients
with HAP and VAP were MDR (91.6% and 94.2%, respectively).
Although there was a difference in the rates of susceptibility to
antimicrobial drugs between the two groups, it has not reached
level of statistical significance.
Isolates of P. aeruginosa from HAP and VAP showed low degree
of susceptibility to ciprofloxacin and gentamicin (below 10%),
followed by amikacin (25%), while the rate of susceptibility to
742 Z.M. Djordjevic et al. / Journal of Infection and Public Health 10 (2017) 740–744

Table 1
Causes of hospital-acquired and ventilator-associated pneumonia in ICU of the Clinical Centre Kragujevac, Serbia, 2009–2015.

Microorganism 2009 2010 2011 2012 2013 2014 2015 Total

Gram-negative bacteria (n = 936)

Acinetobacter spp. 21 (41.2)a 52 (27.4) 69 (35.4) 76 (51.0) 65 (44.2) 41 (46.6) 58 (35.6) 382 (38.9)
Pseudomonas aeruginosa 14 (27.5) 42 (22.1) 53 (27.2) 42 (28.2) 33 (22.4) 11 (12.5) 36 (22.1) 231 (23.5)
Enterobacter spp. 2 (3.9) 3 (1.6) 23 (11.8) 11 (7.4) 1 (0.7) 10 (11.4) 14 (8.6) 64 (6.5)
Klebsiella pneumoniae 3 (5.9) 37 (19.5) 7 (3.6) 0 (0) 3 (2.0) 6 (6.8) 6 (3.7) 62 (6.3)
Klebsiella spp. 3 (5.9) 5 (2.6) 11 (5.6) 5 (3.4) 17 (11.6) 4 (4.5) 10 (6.1) 55 (5.6)
Proteus mirabilis 2 (3.9) 7 (3.7) 7 (3.6) 3(2.0) 5 (3.4) 8 (9.1) 22 (13.5) 54 (5.5)
Stenotrophomonas maltophilia 2(3.9) 24 (12.6) 1 (0.5) 0 (0) 10 (6.8) 1 (1.1) 0 (0) 38 (3.9)
Escherichia coli 2 (3.9) 5 (2.6) 6 (3.1) 3 (2.0) 6 (4.1) 1 (1.1) 4 (2.5) 27 (2.7)
Proteus vulgaris 0 (0) 7 (3.7) 1 (0.5) 0 (0) 0 (0) 1 (1.1) 1 (0.6) 10 (1.0)
Otherb 0 (0) 3 (1.6) 1 (0.5 1 (0.7) 2 (1.4) 4 (4.5) 2 (1.2) 13 (1.3)

Gram-positive bacteria (n = 47)

Staphylococcus aureus 2 (3.9) 3 (1.6) 15 (7.7) 8 (5.4) 4 (2.7) 1 (1.1) 9 (5.5) 42 (4.3)
Coagulase-negative s taphylococci 0 (0) 2 (1.1) 1 (0.5) 0 (0) 1 (0.7) 0 (0) 1 (0.6) 5 (0.5)
a
Percentage in parenthesis was calculated in relation to the total number of isolates/year.
b
Includes: Providentia spp. (6 isolates), Seratia spp. (4 isolates) and Citrobacter spp. (3 isolates).

Table 2
Percentage of antimicrobial susceptibility among the most common causative agents of hospital-acquired pneumonia in the ICU of the Clinical Centre Kragujevac.

Microorganism Antibiotica

AMC TAZ CTR CEF CFM IMP MER GEN AMC CIP

Acinetobacter spp. (n = 130) 26.7 13.6 0.0 0.0 17.9 19.7 18.0 5.9 5.0 5.0
Pseudomonas aeruginosa (n = 87) 8.3 72.8 2.5 12.2 33.3 35.3 34.9 6.1 24.4 9.9
Enterobacter spp. (n = 23) 0.0 25.0 5.0 5.3 42.9 63.6 63.6 25.0 31.8 25.0
Klebsiella pneumoniae (n = 18) 0.0 53.8 0.0 0.0 16.6 50.0 47.1 0.0 18.7 5.9
Klebsiella spp. (n = 17) 9.1 50.0 0.0 0.0 33.3 70.6 68.7 5.9 47.1 7.1
Proteus mirabilis (n = 15) 7.7 33.3 7.3 9.1 46.7 60.0 73.3 38.5 40.0 50.0
Stenotrophomonas maltophilia (n = 14) 40.0 15.4 0.0 7.1 46.2 7.1 7.1 0.0 0.0 14.3
a
AMC—Amoxicillin + clavulanic acid, TAZ—Piperacillin-tazobactam, CTR—ceftriaxone, CEF—ceftazidime, CFM—cefepime, IMP—imipenem, MER—meropenem,
GEN—gentamicin, AMC—amikacin, CIP—ciprofloxacin.

Table 3
Percentage of antimicrobial susceptibility among the most common causative agents of ventilator-associated pneumonia in the ICU of the Clinical Centre Kragujevac.

Microorganism Antibiotica

AMC TAZ CTR CEF CFM IMP MER GEN AMC CIP

Acinetobacter spp. (n = 252) 16.7 11.5 0.4 0.0 19.1 15.1 14.7 8.2 7.7 6.2
Pseudomonas aeruginosa (n = 144) 16.0 70.5 1.5 7.9 30.8 35.7 29.8 4.4 25.4 11.7
Enterobacter spp. (n = 41) 3.3 41.2 2.9 0.0 32.5 64.1 66.7 11.8 33.3 7.7
Klebsiella pneumoniae (n = 44) 5.7 39.5 0.0 0.0 17.1 43.2 37.2 0.0 15.0 9.8
Klebsiella spp. (n = 38) 4.0 50.0 0.0 0.0 37.8 43.2 37.8 10.3 26.3 16.2
Proteus mirabilis (n = 39) 6.3 52.9 0.0 0.0 41.2 60.5 62.2 36.1 18.4 28.9
Stenotrophomonas maltophilia (n = 24) 11.1 4.2 0.0 0.0 30.4 8.7 8.7 11.1 9.5 4.5
a
AMC—Amoxicillin + clavulonic acid, TAZ—Piperacillin-tazobactam, CTR—ceftriaxone, CEF—ceftazidime, CFM—cefepime, IMP—imipenem, MER—meropenem,
GEN—gentamicin, AMC—amikacin, CIP—ciprofloxacin.

carbapenems and 4th generation cephalosporin was 30–35%. Fur- Discussion

thermore, 86% of the carbapenem-resistant isolates of P. aeruginosa
were also resistant to ciprofloxacin. The highest level of sensitivity
from both groups was retained toward piperacillin-tazobactam (up
to 70% of isolates were susceptible). Nearly 85% of the P. aeruginosa
isolates from both groups were MDR. The rates of susceptibiilty to
antibiotics in both groups were not significantly different.
Other Gram-negative bacteria also showed low rate of sus-
ceptibility to the tested antibiotics, except to carbapenems and
piperacillin-tazobactam. Statistically significant difference in the
rates of susceptibility among the groups was registered only for
Klebsiella spp., since this pathogen showed lower susceptibility to
meropenem in the VAP group (p = 0.038).
Among Gram-positive bacteria the most common isolate was S.
aureus (33 isolates from HAP and 9 from VAP group). The frequency
of methicillin-resistant S. aureus (MRSA) was 45%, but these isolates
were completely susceptible to vancomycin and linezolid (100%)
(data not shown).
In order to initiate appropriate empirical antibiotic regimen
clinicians need to know predominant causative agents of HAP/VAP
in any specific clinical setting or ICU and their drug susceptibility
patterns. Unfortunately, identifying etiological agents of HAP/VAP
may be difficult because it is necessary to distinguish between
mere colonization of the tracheobronchial tree and true pneumo-
nia. Additional challenges, such as the fact that no organism or
alternatively, several organisms, may be isolated, hamper opti-
mal targeted antimicrobial therapy. Therefore, clinicians are too
often in a situation to continue with empirical choice of antibiotics
even after several days of initial empirical therapy, and regularly
updated knowledge of local susceptibility patterns is then the only
stronghold they can rely on when making therapeutic decisions.
Results of our study showed that over 95% of isolates from
the patients with HAP/VAP belong to Gram-negative bacteria, and
more than 60% of Gram-negatives were Acinetobacter spp. and P.
aeruginosa. These two bacterial species are well known by their low
 Z.M. Djordjevic et al. / Journal of Infection and Public Health 10 (2017) 740–744
susceptibility to multiple antibiotics, and unless appropriate antibi-
otic therapy is administered early, mortality is high [16]. Resistance
is mostly mediated by multiple efflux pumps expressed intrinsi-
cally or up regulated by mutation [17]. Increase in frequency of
MDR isolates of Acinetobacter spp. and P. aeruginosa was observed
in many countries, and some MDR isolates are susceptible only to
polymyxin B [18].
However, not all studies presented results similar to ours. In the
study of Jones [19] which summarized experience of the SENTRY
Antimicrobial Surveillance Program during the period 1997-2008
from the data retrieved for hospitalized patients with pneumonia
from North America, Europe, and Latin America (31436 total cases),
6 organisms (S. aureus (28.0%), P. aeruginosa (21.8%), Klebsiella spp.
(9.8%), Escherichia coli (6.9%), Acinetobacter spp. (6.8%), and Enter-
obacter spp. (6.3%)) caused 80% of episodes. It is not surprising,
since differences in antimicrobial flora and susceptibility patterns
can vary considerably between regions, countries, hospitals, ICUs
and specimen sources. This was illustrated by the observational
study that compared quantitative culture results obtained by bron-
choscopy from 229 patients with VAP at 4 different institutions:
there was wide variation in both frequency of pathogens and pat-
terns of susceptibility to antibiotics among the institutions [20].
One of possible explanations of high frequency of Acinetobacter spp.
and P. aeruginosa isolates in our study could be an organizational
matter which is specific for Clinical Centre Kragujevac: the patients
are never directly admitted to the central ICU, but are rather trans-
ferred either from Emergency Center or from other hospital wards.
Therefore, they usually were already treated by antibiotics for sev-
eral days in the moment of admission to the central ICU, which
could select Acinetobacter spp. and P. aeruginosa as two bacterial
species with the highest potential for rapid induction of resis-
tance to multiple antibiotics. The risk factors for HAP/VAP caused
by Acinetobacter spp. observed in other studies, like prolonged
mechanical ventilation, presence of a central venous catheter, or
Candida spp. airway colonization, were either not registered or fol-
lowed in our study [21].
Some recent studies [22] presented results similar to ours,
where the commonest isolated pathogens were A. baumannii
(21.1%) and P. aeruginosa (17.4%), while the third place belonged
to S. aureus (15.8%). The systematic review [23] which analyzed 22
studies of VAP in developing countries, found that Gram-negative
bacilli were responsible for majority of VAP episodes (41–92%).
Overall, P. aeruginosa and Acinetobacter spp. were the most common
isolated Gram-negative organisms (9–52% and 0–36%, respec-
tively). Gram-positive cocci were responsible for 6–58% of the
isolates. Probably the settings where these studies were performed
were burdened with overutilization of antibiotics (which led fur-
ther to selection of resistant Acinetobacter spp. and P. aeruginosa),
since developing countries in general less adhere to evidence-based
guidance for prescribing of antibiotics.
Early appropriate antibiotic therapy for HAP/VAP was investi-
gated in large number of observational studies and was associated
with reduced mortality [24,25]. Since our study showed that iso-
lates taken from patients with HAP have low rates of susceptibility
to ceftriaxone (0–5%), fluoroquinolones (5–25%) and were often
MDR (85–91% for most common pathogens), empirical therapy
should be initiated with carbapenems or piperacillin-tazobactam
or colistin (if Acinetobacter spp. is suspected as etiological agent)
in combination with anti-pseudomonal fluoroquinolone or amino-
glycoside [11]. Furthermore, since isolates derived from patients
with VAP in our study have low rate of susceptibility to the
most commonly used antibiotics and include MDR pathogens
(85–95%), initial empiric therapy of VAP should also include com-
bination of an anti-pseudomonal cephalosporin or carbapenem
or piperacillin-tazobactam with an anti-pseudomonal fluoro-
quinolone or aminoglycoside. If Acinetobacter spp. is suspected to
743
be causative agent, colistin should be used instead of carbapenem
or piperacillin-tazobactam. Such therapy is active not only against
P. aeruginosa and Acinetobacter spp., but also against other causative
agents of VAP isolated in our study (Enterobacter, Klebsiella,
Stenotrophomonas maltophilia and methicillin-sensitive S. aureus-
MSSA). Prescribing two anti-pseudomonal agents, from different
classes, is needed to assure that ≥95% of patient receive empiric
therapy active against likely pathogens. However, among the
anti-pseudomonal cephalosporins, ceftazidime should be avoided,
because almost 100% of the most frequent isolates in our study were
resistant to this antibiotic. The above mentioned recommenda-
tions apply to our institution only with our specific local resistance
patterns, and other institutions should base recommendations for
empiric choice of antibiotic on their own local resistance patterns.
Low rates of susceptibility of pathogens HAP/VAP to common
antibiotics were shown in other studies, too [19]. Surveillance
studies from United States which analyzed data of the National
Healthcare Safety Network (NHSN) during 2009–2010, suggested
that among isolates of VAP 71.6% P. aeruginosa were susceptible
to cefepime, 69.8% to carbapenems and 80.9% to piperacillin-
tazobactam, while 38.8% of A. baumannii were susceptible to
carbapenems and 51.6% of S. aureus were susceptible to methicillin
[26]. Haeili et al. [22] also demonstrated low susceptibility rate of A.
baumani to imipenem (25%), cephalosporins (3–25%), aminoglyco-
sides (12–50%) and ciprofloxacin (below 35%), while susceptibility
to polymyxin B was preserved (95.5%). Besides, P. aeruginosa also
was poorly susceptible to tested antibiotics, and its susceptibility to
imipenem decreased durig the study from 80% to 40%. The authors
suggested prescribing polymyxin B and piperacillin-tazobactam as
the first choice for HAP and VAP (susceptibility rates 89.2% and
80.3%, respectively). However, susceptibility rates in our study
were even lower, and this could be explained by several reasons:
(1) although local antibiotic guidelines exist in the study settings,
they were never implemented in practice; (2) fear of litigation urges
clinicians to prescribe antibiotics in situations when an infection is
only suspected, leading to high rate of unnecessary use of antibi-
otics: (3) antibiotic stewardship was lacking in the study settings.
Low susceptibility rates to antibiotics of isolates from patients with
HAP or VAP, as well as the fact that current HAP/VAP guidelines are
not specific enough in their definitions and recommendations, sug-
gest the need for introduction of antibiotic stewardship in clinical
practice of developing countries. Only carefully planned, coordi-
nated and sustained efforts of a team of various specialists involved
in everyday fight against infections occurring in ICUs may improve
treatment success and increase susceptibility of bacteria to antibi-
otics in the long run.
Our study had one more very important finding: susceptibility
rates to tested antibiotics were not significantly different between
HAP and VAP isolates, except for meropenem in Klebsiella spp.
(p = 0.038) where susceptibility in the VAP group was lower than
in the HAP group (62.2% vs. 31.3%). However, Klebsiella spp. was
isolated in only 5.6% of cases. Therefore, in the settings like ours,
empirical therapy (as previously stated) should be the same for
both HAP and VAP.
Although in our study S. aureus was isolated from only 4.3%
patients, 45% of the isolates were MRSA. This urges early recogni-
tion of patients with risk factors for MRSA infections and addition
of vancomycin, teicoplanin or linezolide to empiric antibiotic regi-
men in such patients. According to current guidelines [9] patients
with risk factor for MRSA infection are: patients with prior intra-
venous antibiotic use within 90 days, hospitalization in a unit with
high or unknown prevalence of MRSA, and high risk for mortality
(including need for ventilatory support due to pneumonia and sep-
tic shock). Luckily, our study showed 100% susceptibility of MRSA to
vancomycin, teicoplanin or linezolide, so additional efforts should
be made to preserve efficacy of these antibiotics. Of note, pro-
744 Z.M. Djordjevic et al. / Journal of Infection and Public Health 10 (2017) 740–744
posed agents included in empiric regimens for HAP/VAP in our
ICU due to their activity against gram-negative bacilli are also suit-
able for empiric coverage against MSSA (piperacillin-tazobactam,
cefepime, levofloxacin, imipenem and meropenem), so it is not
necessary to use vancomycin, teicoplanin or linezolide for MSSA.
In conclusion, empiric antibiotic therapy of HAP and VAP in ICU
should be based both on evidence-based guidelines and on data
about antibiotic susceptibility patterns of the local flora. In ICU
with predominance and high resistance rates of Gram-negative
pathogens, patients with HAP or VAP should be initially treated
with combination of carbapenem or piperacillin-tazobactam with
an anti-pseudomonal fluoroquinolone or aminoglycoside. Colistin
should be used instead if Acinetobacter spp. is suspected. Van-
comycin, teicoplanin or linezolide should be added only in patients
with risk factors for infections with MRSA.
Funding
No funding sources.
Competing interests
None declared.
Ethical approval
The study was approved by the Ethics Committee of Clinical
Centre Kragujevac.
Acknowledgement
This study was partially financed by Research grant No. 175007
given by Serbian Ministry of Education, Science and Technological
Development.
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