Content uploaded by Francesco D'Aleo
Author content
All content in this area was uploaded by Francesco D'Aleo on Dec 18, 2018
Content may be subject to copyright.
1Corre spon ding Aut hor : Flavia D’anDrea, MD; e-Mail: Flavia.DanDre a91@lib ero.it
INTRODUCTION
Pseudomonas aeruginosa is an aerobic gram-negative
bacterium and one of the most common nosocomial
pathogens1. It is ubiquitous in many different environ-
mental settings such as water, soil and plants2. The blue-
green coloration produced during culture is a peculiar
characteristic from which its name derives: in 1869
Fordos rst identied the cause of this coloration, ex-
tracting the blue pigment called “pyocyanin”. In 1882,
Carle Gessard described the growth of the bacterium
from cutaneous wounds of two patients with blue-green
pus3. P. aeruginosa is involved in a variety of nosoco-
mial infections including hospital-acquired pneumonia
(HAP), urinary tract infections and central line-associ-
ated bloodstream infection. Urinary tract infections are
the most common, lower respiratory tract and blood-
stream infections are the most lethal4. It is also the most
important cause of chronic lung infections contributing
to the mortality of patients with cystic brosis5. Risk
ABSTRACT:
—
Objective: Pseudomonas aeruginosa is one of the principal causes of bacterial infections in healthcare
and it represents a critical problem worldwide. Infections are becoming more difficult to treat because
this bacterium is resistant to many commonly used antibiotics, including aminoglycosides, cephalospo-
rins, fluoroquinolones and carbapenems. Drug resistance is associated with worse clinical outcomes:
it facilitates prolonged hospitalization, multiple morbidities and increased health costs. The aim of this
work was to evaluate the epidemiology of Pseudomonas aeruginosa during the years 2015-2017 in “G.
Martino” University Hospital of Messina (Messina, Italy).
—
Materials and Methods: We carried out an epidemiological study, collecting all the reports of P. ae -
ruginosa isolates and relative resistances at the Microbiology Laboratory of the University Hospital “G.
Martino” in Messina (Italy) during a three years period (2015-2017).
—
Results: In our hospital, Pseudomonas spp. detection rates are equal to 14.6%, 12.3% and 13.3% of all mi-
crobial isolates in 2015, 2016 and 2017, respectively. During 2017, the Intensive Care Unit showed the highest
mean percentages of Pseudomonas spp. detection (25%), followed by surgical area (18.4%) and medical area
(22.2%). The percentages of resistance strains detection showed a decreasing trend in the considered period.
—
Conclusions: Our study shows that, despite a decreasing trend during these three years period, P. ae-
ruginosa infection still represents an important cause of healthcare-associated infections in our hospital.
It is necessary to improve preventive measures to reduce the incidence of this infection.
—
Keywords: Pseudomonas aeruginosa, Infection, Healthcare-Associated Infections, Antibiotic resis-
tance, Epidemiology.
1
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
2
Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
3
Department of Human Pathology of the Adult and the Developmental Age “G. Barresi”, University of Messina,
Messina, Italy
F. D’Andrea and I. A. Paolucci equally contributed to the work
F. D’Andrea1, I. A. Paolucci1, M. Ceccarelli1,2, F. d’Aleo1, D. Iannello3,
A. Facciolà1, G. Mancuso1, E. Venanzi Rullo1,2, G. F. Pellicanò3
Pseudomonas aeruginosa
detection
in South Italy:
an epidemiological survey
Infect DIs trop MeD 2018; 4 (4): e507
Infect DIs trop MeD
2
sist in many countries, especially in the Eastern and
South-Eastern parts of Europe. The highest mean resis-
tance percentage in 2017 was reported for uoroquino-
lones (20.3%), followed by piperacillin ± tazobactam
(18.3%), carbapenems (17.4%), ceftazidime (14.7%)
and aminoglycosides (13.2%) (Table I). In Table II, the
Italian situation is presented: also, in this case the high-
est mean resistance percentage in 2017 is described for
uoroquinolones (25.1%), followed by piperacillin ±
tazobactam (24.2%), ceftazidime (20%), carbapenems
(19.9%) and aminoglycosides (18%). The aim of this
retrospective cross-sectional study is to evaluate the
prevalence of resistant strains of P. aeruginosa in the
University Hospital “G. Martino” of Messina (Messi-
na, Italy) and compare our epidemiological situation
with the national and international ones.
MATERIALS AND METHODS
We carried out a cross-sectional study collecting anti-
microbial-resistances of P. aeruginosa isolated in the
Messina University Hospital “G. Martino” during the
three years period 2015-2017. The data were provided
by the Local Microbiology Laboratory. Anti-microbial
susceptibility tests were obtained using Vitek 2.0 auto-
matic system (Biomerieux, Florence, Italy). Data were
analyzed with descriptive statistics (mean, percentage,
standard deviation).
RESULTS
In the considered three years period, in our hospital, we
observed Pseudomonas spp. detection rates amounting
to 14.6%, 12.3% and 13.3% of all microbial isolates in
2015, 2016 and 2017, respectively. The percentages of its
factors for P. aeruginosa infection include impairment
of the immune system, prolonged hospitalization, pro-
longed antimicrobial therapy, and mechanical ventila-
tion. Patients who underwent organ transplantation,
invasive procedures (such as tracheostomy) or immuno-
suppressive therapy, patients with catheters or subjected
to surgical intervention are more susceptible to infec-
tion, causing higher morbidity and mortality among
them6. Transmission through contaminated medical de-
vices, healthcare workers’ hands and patient-to-patient
transmission represent a well-established mechanism
of its spreading. Moreover, the persistence of P. aer ugi-
nosa is facilitated by hospital reservoirs such as breath-
ing and hemodialysis devices, sinks, water, bathrooms,
surfaces7-10.
P. aeruginosa represents a critical problem and a
challenge in medical practice worldwide: infections
are becoming more difcult to treat because this
bacterium is resistant to many commonly used anti-
biotics, including aminoglycosides, cephalosporins,
uoroquinolones and carbapenems11. Drug resistance
is associated with worse clinical outcomes: it facili-
tates prolonged hospitalization, multiple morbidities
and increased health costs12-15. This pathogen is not
only intrinsically resistant to a wide range of antimi-
crobials, but it is also capable to develop resistance
to commonly used antimicrobials through acquired
mutations in chromosomal genes16-18 . Intrinsic drug
resistance is mainly due to low outer membrane per-
meability, the expression of efux pumps and the pro-
duction of enzymes conferring resistance to β-lactam
and aminoglycoside antibiotics19-25. Antibiotics includ-
ing β-Lactams, aminoglycosides, uoroquinolones
and carbapenems can enter cells by diffusing through
porins of the outer membrane22,23. P. aeruginosa limits
antibiotic entry acting on the outer membrane permea-
bility, reducing the number of non-specic porins and
replacing them with specic or more-selective chan-
nels25. The outer membrane of Pseudomonas, thus, be-
comes an effective barrier to the mentioned antibiotics.
Reduction in drug accumulation can also be achieved
through active export by membrane-associated pumps.
Efux pumps confer resistance to different antibiotics:
MexAB-OprM and MexXY-OprM confer resistance
to uoroquinolones, aminoglycosides, tetracyclines
and β-lactams. MexAB-OprM also confers resistance
to meropenem (but not imipenem) and MeXY-OprM
acts against cefepime but not ceftazidime19,26,27. At
last, P. aeruginosa produces an AmpC-like inducible
chromosomal b-lactamase that can inactivate b-lact-
ams: AmpC overproduction can lead to an increased
resistance20, 21. Acquired resistance genes are mostly in-
volved in resistance to b-lactams, aminoglycosides and
carbapenems: strains able to product extended-spec-
trum βlactamases (ESBL) and metallo-β-lactamases
have spread worldwide28. Intensive Units Care are the
settings where outbreaks are more often registered2 9,30.
European surveillance data31 show signicantly de-
creasing trends in resistance for P.aeruginosa for all
antimicrobial groups under surveillance during the
period 2014 to 2017. High resistance percentages per-
Table 1. Revised from ECDC, 2018. Percentages of resistance to
antibiotics in Europe (2015-2017)31.
2015 2016 2017
Piperacilline/Tazobactam 19.9% 18.8% 18.3%
Fluoroquinolones 20.9% 18.8% 20.3%
Ceftazidime 15.4% 14.4% 14.7%
Aminoglycosides 15.3% 14.1% 13.2%
Carbapenems 19.4% 18.2% 17.4%
Table 2. Revised from ECDC, 2018. Percentages of resistance to
antibiotics in Italy (2015-2017)31.
2015 2016 2017
Piperacilline/Tazobactam 29.5% 30.7% 24.2%
Fluoroquinolones 24.6% 24.7% 25.1%
Ceftazidime 21.7% 23% 20%
Aminoglycosides 17.2% 19.1% 18%
Carbapenems 23% 23.5% 19.9%
P. aerugin osa Prevalenc e in a third level hosPital
3
cultures and in 2017 the 3.6% of total positive blood cul-
tures (Table IV).
We then evaluated the rate of detection of resistance
strains. Figure 2 shows the percentages of resistance
to ceftazidime, piperacilline/tazobactam, uoroquino-
lones, aminoglycosides and carbapenems. As it can be
observed from the gure, the percentages of resistance
strains detection showed a decreasing trend in the con-
sidered period.
DISCUSSION
Antimicrobial resistance is recognized as a major public
health burden worldwide32,33. Multidrug-resistant (MDR)
P. aeruginosa is associated with worse outcomes, higher
mortality and increased health costs5,12,16 ,34, 35. In our hos-
pital we observed a decrease of P. aeruginosa detection,
with a percentage of 13.3% in 2017 (Figure 1). Our study
showed that the overall percentages of resistance to anti-
biotics decreased during these three years period in our
hospital, in line with European and Italian data processed
by ECDC31 (Table I-III). Control of Pseudomonas infec-
tions requires strategies for risk factors early identica-
tion, detection of resistant organisms and implementation
of prevention strategies. Several studies7,12 ,3 6- 40 show the
importance of Pseudomonas transmission between pa-
tients by healthcare workers (HCWs)’s hands: hand hy-
giene using alcohol-based products is one of the most
helpful and, at the same time, simplest practice to reduce
P. aeruginosa and MDRs pathogens spread. Training
courses for doctors, nurses, cleaning staff are needed to
reach a greater awareness: use of alcohol-based products,
disposable gowns and gloves and patient’s isolation in a
single room are three of the main recommendations to
control the transmission. Healthcare environment is a
Pseudomonas reservoir: its early identication and its
subsequent decontamination are another way to control
its spreading. Infection control practices must involve all
the hospital departments, mainly focusing on the most
critical.
detection compared to all the microbial isolates in all the
entire hospital are shown in Figure 1. The percentages
of Pseudomonas aeruginosa detection in the Hospital
wards in 2015, 2016 and 2017 are shown in Table III.
Fibrosis cystic ward always showed the highest percent-
ages of P. aeruginosa detection, followed by Pediatric
ICU. In 2017, emergency area showed the highest mean
percentages of P. aeruginosa detection (25%), followed
by surgical area (18.4%) and medical area (22.2%).
During the study period, we also observed the occur-
rence of isolated of P. aeruginosa from blood cultures.
Our data show that in 2015 the P. aeruginosa isolates
represented the 3.6% of total positive blood cultures; in
2016 the isolates were the 2.7% of total positive blood
Figure 1. Percentages of P. aeruginosa de-
tection rates isolated in all the Hospital in
the three years period 2015-2017.
Table 3. Percentages of PA detection in the various wards of the
three considered areas.
2015 2016 2017
Surgical Area
General Surgery 23 10 12.5
Oncological Surgery 14.6 8.1 11.6
Neurosurgery 13.2 14 25.5
Pediatric surgery 25.5 15 27.8
Plastic Surgery 7.7 28.6 15.5
Thoracic Surgery 27.2 23.5 17.5
Vascular Surgery 25.8 20.9 21.3
Orthopaedics 35.4 27 15.2
Medical Area
Gastroenterology/ 83 74 78.6
Cystic Fibrosis
Geriatrics 16 17.1 22
Infectious diseases 27.7 34.7 12.1
Internal Medicine 15 14.2 17.2
Nephrology 13.3 13.1 10
Neurology 25 5.8 11
Pulmunology 12.2 26 22
Oncology 23.1 3 5
Emergency Area
Pediatric ICU 66 38.2 41
Cardiological ICU 28.7 28.6 17.7
Adult ICU 16.6 14.3 16.4
Infect DIs trop MeD
4
aeruginosa infections in Asia-Pacic and consequences of in-
appropriate initial antimicrobial therapy: a systematic literature
review and meta-analysis. J Glob Antimicrob Resist 2018; 14:
33- 44.
7. Facciolà A, Ceccarelli M, Paolucci IA, d’Aleo F, Cacopardo B,
Condorelli F, Venanzi Rullo E, Lo Presti Costantino MR, Pel-
licanò GF. MRSA detection in South Italy: an epidemiological
survey to evaluate the burden of this important public health
issue. Infect Dis Trop Med 2018; 4: e486.
8. Blanc DS, Petignat C, Janin B, Bille J, Francioli P. Frequency
and molecular diversity of Pseudomonas aeruginosa upon ad-
mission and during hospitalization: a prospective epidemio-
logic study. Clin Microbiol Infect 1998; 4: 242-247.
9. Pollack M. 1995. Pseudomonas aeruginosa. In G. L. Mandell,
R. Dolan, and J. E. Bennett (ed.), Principles and practices of
infectious diseases. Churchill Livingstone, NY; pp. 1820-2003.
10. Thuong M, A rvaniti K, Ruimy R, de la Salmonière P, Scanvic-
Hameg A, Lucet JC, Régnier B. Epidemiology of pseudomonas
aeruginosa and risk factors for carriage acquisition in an inten-
sive care unit. J Hosp Infect 2003; 53: 274-282.
11. Alou sh V, Navon-Venezia S, Seigma n-Igra Y, Cabili S, Carmeli
Y. Multidrug-resistant pseudomonas aeruginosa: risk factors
and clinical impact. Antimicrob Agents Chemother 2006; 50:
43- 48.
12. d’Aleo F, Venanzi Rullo E, Paolucci IA, Cacopardo B, Fac-
ciolà A, Condorelli F, Ceccarelli M, Mondello P, Pellicanò GF.
Epidemiology of Klebsiella pneumoniae MDR during the years
2015-2017 in “G. Martino” University Hospital of Messina:
preliminary data. Infect Dis Trop Med 2018; 4: e488.
13. D’Aleo F, Ceccarelli M, Facciolà A, Venanzi Rullo E, Paolucci
IA, Lo Presti Costantino MR, Fazii P, Conte M, Pellicanò GF.
Current fast methods for the identication of carbapenemase en-
zymes in clinical laboratory. Infect Dis Trop Med 2018; 4: e470.
CONCLUSIONS
Pseudomonas aeruginosa continues to be an important
public health issue in our hospital and a cause of noso-
comial infections. Optimisation of preventive measures
to reduce this burden is still needed.
ConfliCt of inter est:
The Authors declare that they have no conict of inte-
rests.
REFERENCES
1. McGowan JE Jr. Resistance in nonfermenting gram-negative
bacteria: multidrug resistance to the maximum. Am J Med
2006; 119: S29-S36.
2. Philip D. Lister, Daniel J. Wolter, Nancy D. Hanson. Anti-
bacterial-resistant pseudomonas aeruginosa: clinical impact
and complex reg ulation of chromosomally encoded resistance
mechanisms. Clin Microbiol Rev 2009; 22: 582-610.
3. Gessard, C. Classics in infectious diseases. On the blue and
green coloration that appea rs on bandages. Rev Infect Dis 1984;
6 Suppl 3: S775-S776.
4. Peleg AY, Hooper DC. Hospital-acquired infections due to
Gram-negative bacteria. N Engl J Med 2010; 362: 1804-1813.
5. Fata Moradali M, Ghods S, Ber nd H, Rehm A. Pseudomonas
aeruginosa lifestyle: a paradigm for adaptation, survival, and
persistence. Front Cell Infect Microbiol 2017; 7: 39.
6. Merchant S, Proudfoot EM, Quadri H N, McElroy HJ, Wright
WR, Gupta A, Sarpong EM. Risk factors for pseudomonas
Table 4. Details about positive blood cultures and P. aeruginosa
isolates during the three years of the study.
Years Positive blood Positive for
cultures P. aeruginosa
2015 23% 3.6%
2016 25.4% 2.7%
2017 26.7% 3.6%
Table 5. Percentages of resistance to antibiotics in “G.Martino”
Hospital (2015-2017).
2015 2016 2017
Piperacilline/Tazobactam 33% 22% 1%
Fluoroquinolones 18% 17% 3%
Ceftazidime 22% 30% 5%
Aminoglycosides 11% 10% 4%
Carbapenems 20% 15% 5%
Figure 2. Resistance strains detection during 2015-2017.
P. aerugin osa Prevalenc e in a third level hosPital
5
28. Kaur A, Singh S. Prevalence of extended spectrum betalac-
tamase (ESBL) and metallobetalactamase (MBL) producing
pseudomonas aeruginosa and acinetobacter baumannii isolated
from various clinical samples. J Pathog 2018; 2018: 6845985.
29. Lila G, Mulliqi G, Raka L, Kurti A, Bajrami R, Azizi E. Infect
Drug Resist 2018; 11: 2039-2046.
30. Siwakoti S, Subedi A, Sharma A, Baral R, Bhattarai NR, Khanal
B. Incidence and outcomes of multidrug-resistant gram-negative
bacteria infections in intensive care unit from Nepal- a prospec-
tive cohort study. Antimicrob Resist Infect Control 2018; 7: 114.
31. European Antimicrobial Resistance Surveillance Network
(EARS-Net). 2018. European Centre for Disease Prevention
and Control. http://ecdc.europa.eu/en/activities/surveillance/
EARS-Net/Pages/index.aspx.
32. Bodro M, Sabé N, Tubau F, Lladó L, Baliellas C, Roca J, Cru-
zado JM, Carratalà. Risk factors and outcomes of bacteremia
caused by drug-resistant ESKAPE pathogens in solid-organ
transplant recipients. J Transplantation 2013; 96: 843-849.
33. Kuo HT, Ye X, Sampaio MS, Reddy P, Bunnapradist S. Cy-
tomegalovir us serostatus pairing and deceased donor kidney
transplant outcomes in adult recipients with antiviral prophy-
laxis. Transplantation 2010; 90: 1091-1098.
34. Bergamasco MD, Barroso Barbosa M, de Oliveira GD, Cipullo
R, Moreira JCM, Baia C. Infection with Klebsiella Pneumoniae
carbapenemase (KPC)-producing K. Pneumoniae in solid or-
gan transplantation. Transpl Infect Dis 2012; 14: 198-205.
35. Hu Y, Ping Y, Li L, Xu H, Yan X, Dai H. A retrospective study of
risk factors for carbapenem-resistant Klebsiella Pneumoniae acqui-
sition among ICU patients. J Infect Dev Ctries 2016; 10: 208-213.
36. Luangasanatip N, Luangasanatip N, Hongsuwan M, Lubell Y,
Limmathurotsak ul D, Srisamang P, Day NPJ, Graves N, Coo-
per BS. Cost-effectiveness of interventions to improve hand
hygiene in healthcare workers in middle-income hospital set-
tings: a model-based analysis. J Hosp Infect 2018; 100: 165-175.
37. Ulrich N, Gastmeier P, Vonberg RP. Effectiveness of healthcare
worker screening in hospital outbreaks with gram-negative
pathogens: a systematic review. Antimicrob Resist Infect Con-
trol 2018; 7: 36.
38. Sypsa V, Psichogiou M, Bouzala GA, Hadjihannas L, Hatzakis
A, Daikos GL. Transmission dynamics of carbapenemase-
producing Klebsiella pneumoniae and anticipated impact of
infection control strategies in a surgical unit. PLoS One 2012;
7: e41068.
39. Arinder P, Johannesson P, Karlsson I, Borch E. Transfer and
Decontamination of S. aureus in transmission routes regarding
hands and contact surfaces. PLoS One 2016; 11: e0156390.
40. Barnes SL, Morgan DJ, Harris AD, Carling PC, Thom KA.
Preventing the transmission of multidrug-resistant organisms:
modeling the relative importance of hand hygiene and environ-
mental cleaning inter ventions. Infect Control Hosp Epidemiol
2014; 35: 1156 -1162 .
.
14. Lautenbach E, Synnestvedt M, Weiner MG, Bilker WB, Vo L,
Schein J, Kim M. Imipenem resistance in Pseudomonas aeru-
ginosa: emergence, epidemiology, and impact on clinical and
economic outcomes. Infect Control Hosp Epidemiol 2010; 31:
47-53.
15. Cama BAV, Venanzi Rullo E, Condorelli F, Cacopardo B,
D’Aleo F, Facciolà A, Pellicanò GF, Ceccarelli M. Nosocomial
Citrobacter koseri urosepsis in an 87-year-old woman: a case-
report. Infect Dis Trop Med 2018; 4: e484.
16. Hancock RE. Resistance mechanisms in Pseudomonas aerugi-
nosa and other nonfermentative gram-negative bacteria. Clin
Infect Dis 1998; 27: S93-S99.
17. Livermore DM. Multiple mechanisms of antimicrobial resis-
tance in Pseudomonas aeruginosa: our worst nightmare? Clin
Infect Dis 2002; 34: 634-640.
18. Poole K. Aminoglycoside resistance in Pseudomonas aerugi-
nosa. Antimicrob Agents Chemother 2005; 49: 479-487.
19. Pan YP, Xu YH, Wang ZX, Fang YP, Shen JL. Overexpression
of MexAB-OprM efux pump in carbapenem-resistant Pseu-
domonas aer uginosa. Arch Microbiol 2016; 198: 565-571.
20. Campbell J I, Ciofu O, Hoiby N. Pseudomonas aeruginosa
isolates from patients with cystic brosis have different beta-
lactamase expression phenotypes but are homogeneous in the
ampC-ampR genetic region. Antimicrob Agents Chemother
1997; 41: 1380-138 4.
21. Tam VH, Chang KT, Schilling AN, LaRocco MT, Genty LO,
Garey KW. Impact of AmpC overexpression on outcomes of
patients with Pseudomonas aeruginosa bacteremia. Diagn Mi-
crobiol Infect Dis 2009; 63: 279-285.
22. Hancock RE, Brink man FS. Function of pseudomonas porins
in uptake and efux. Ann Rev Microbiol 2002; 56: 17-38.
23. Köhler T, Michea-Hamzehpour M, Epp SF, Pechere JC. Car-
bapenem activities against Pseudomonas aeruginosa: respec-
tive contributions of OprD and efux systems. Antimicrob
Agents Chemother 1999; 43: 424-427.
24. Margaret BS, Dr usano GL, Stand iford HC. Emerge nce of resis-
tance to carbapenem antibiotics in Pseudomonas aeruginosa. J
Antimicrob Chemother 1989; 24: 161-167.
25. Van Bambeke F, Balzi E, Tulkens PM. Antibiotic efux pumps.
Biochem Pharmacol 2000; 60: 457-470.
26. Jorth P, McLean K, Ratjen A, Secor PR, Bautista GE, Rav-
ishankar S, Rezayat A, Garudathri J, Har rison JJ, Har wood
RA, Penewit K, Waalkes A, Singh PK, Salipante SJ. Evolved
aztreonam resistance is multifactorial and can produce hyper-
virulence in pseudomonas aer uginosa. MBio 2017; 31: 8(5) pii:
e00 517-17.
27. Olivares Pacheco J, Alvarez-Ortega C, Alcalde Rico M, Mar-
tínez JL. Metabolic compensation of tness costs is a gen-
eral outcome for antibiotic-resistant pseudomonas aeruginosa
mutants overexpressing efux pumps. MBio 2017; 8(4) pii:
e00500-17.
