Download Naglaa Mohahmed Ahmad Mohamed Gad_Disscusion

Discussion
DISCUSSION
Antimicrobial resistance among bacterial pathogens is a global
problem, but in Egypt data are sparse. This study reviewed the
antimicrobial susceptibility patterns of nosocomial
isolates of gram
positive cocci and gram-negative bacilli in Benha University Hospitals,
Egypt, from 2009 to 2010.
Although data stratified by hospitals are not presented in details,
resistance among gram-positive cocci and gram negative bacilli was
widespread.
The isolated bacteria in Benha hospitals, in this study were
Klebsiellae spp. (28.9%), E.Coli (18.7%) , Staphylococcus aureus
(15.4%), CONS (11.3%) , Enterococcus spp. (4.8%) , proteus spp.
(4.5%), Enterobacter spp. (4.2%), Pseudomonas spp. (3.7%)
Acinetobacter spp. (1.2%) , on the other hand
and
Yen Tan et al .,(2008)
found in the fourth quarter of 2007 that the isolated bacteria in Singapore
hospitals were E.Coli (22%), Staphylococcus aureus (16%), Klebsiellae
spp. (12%) , Pseudomonas aeruginosa (9%), Enterococcus spp .(5%)
and Acinetobacter spp. (3%).
We observed a high rate of Klebsiellae infection (45.2%) in
neonatal ICU, followed by E.Coli (14.6%), Staphylococcus aureus
(13.4%) and CONS (9.7%). This was against the results of Monsef and
Eghbalian, (2010) were they found that the
most common
microorganisms were E.Coli (66.7%), Klebsiellae spp. (10.5%), followed
by CONS and Staphylococcus aureus, also the results of Yalaz et al.,
(2006)
in
which
the
isolated
bacteria
were
CONS
(31.3%),
Staphylococcus aureus (13%) ,and Klebsiella Pneumoniae (10.5%) in
descending order.
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Discussion
Klebsiellae and CONS
were the most frequently isolated
pathogens from blood each representing (69.4%) and (38.7%)
respectively, El Kholy et al., (2003) found that Enterobacter spp. and
CONS were the frequently isolated pathogens from blood cultures.
The development of a nosocomial infection is a chain of events,
which is influenced by the microbe, transmission route, and the patient
himself (Gaynes and Horan, 2005).
The organisms causing most nosocomial infections usually come
from the patient's own body (endogenous flora). They also can come
from contact with staff (cross-contamination), contaminated instruments
and needles, and the environment (exogenous flora) (Garner et al., 1996).
In our study we collected (205) nosocomial samples, (74) were
tested by sensititer, of which (54) were gram negative and (20) were gram
positive. They were collected from ICU, surgery, dialysis and internal
medicine units. Different samples were collected from blood, respiratory
tract, urinary tract, surgical wounds and deep pus in descending order of
frequency.
Hospital-acquired infections are most commonly associated with
invasive medical devices or surgical procedures. In the present
study
bloodstream infections and lower respiratory tract were the most lethal,
and this was consistent with the results of Peleg and Hooper, (2010).
However
in their study they reported that urinary tract infections were
the most common, but blood stream infections were the most common
in our study.
A range of gram-negative organisms are responsible for hospitalacquired infections, the Enterobacteriaceae family being the most
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Discussion
commonly identified group overall. Unfortunately, multidrug-resistant
organisms,
including
baumannii, and
Pseudomonas
aeruginosa,
Acinetobacter
ESBL–producing or carbapenemase-producing
Enterobacteriaceae, are increasingly being reported worldwide (Peleg
and Hooper, 2010).
In the present study gram negative bacteria
were responsible for
about (26.4%) of hospital acquired infections, and these bacteria
predominate in septicemia (51.8%) and ventilator-associated pneumonia
(25.9%). Recent data from the U.S. National Healthcare Safety Network
indicate that gram-negative bacteria were responsible for more than 30%
of hospital-acquired infections and these bacteria predominate in cases of
ventilator-associated pneumonia (47%) and urinary tract infections (45%)
(Hidron et al., 2008).
In ICUs in the United States, gram-negative bacteria account for
about 70% of these types of infections and similar data were reported
from other parts of the world (Gaynes and Edwards , 2005).The present
study augmented these data, as we found that the rate of gram-negative
bacterial infections in ICUs were (76.3%).
In the present study (62.3%) of hospital-acquired bloodstream
infections in ICUs were due to gram-negative organisms, while it was
approximately (30%) in the United States (Gaynes
and
Edwards,
2005).Although this proportion was lower when hospital-wide data were
examined in the study of Hidron et al.,(2008). This may be explained by
the fact that we collected a small number of nosocomial isolates relative
to the number collected in the previous studies.
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Discussion
Regarding the organisms recovered in our study, all the (18)
klebsiellae spp. isolates from blood (14 Klebsiella pneumonia, 1
Klebsiella oxytoca and 3 klebsiella group 47) were (100%) resistant to
third generations cephalosporins. Among Klebsiella pneumonia 57.2%
were imipenem
resistant, while
Two
3 klebsiella group 47 strains were resistant to both
out
of
71.4% were meropenam
resistant.
carbapenems.
On the other hand of bloodstream isolates of Klebsiella
pneumoniae from hospitals throughout the United States, 27.1% from 483
isolates tested were resistant to third-generation cephalosporins and
10.8% from 452 isolates tested were resistant to carbapenems (Hidron
et al., 2008).
Higher rates of resistance were reported from parts of
Europe (Souli et al., 2008).
In our study 7 out of 14 Klebsiella pneumoniae strains and 2
klebsiella group 47 strains that were resistant to all currently available
antibiotics included in our sensititer panel ,but not including polymyxins,
were recovered from neonatal ICU. The most recent challenge has been
the spread of carbapenemase-producing Enterobacteriaceae. The βlactamase responsible for this phenotype, known as Klebsiella
pneumoniae carbapenemase, or KPC, confers reduced susceptibility to all
cephalosporins (including cefepime), monobactams (aztreonam), and the
carbapenems (Nordmann
Enterobacteriaceae
et al., 2009). Carbapenemase-producing
have now been identified in hospitals in at least 20
states in the United States, as well as in other parts of the world, including
South America, Israel, China, and, less commonly, Europe (Nordmann et
al., 2009). The genetic relatedness of the strains responsible for outbreaks
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Discussion
within and between countries highlights the importance of strict infection
control to prevent ongoing dissemination (Navon-Venezia et al., 2009).
These β-lactamases are encoded on mobile genetic elements,
mostly plasmids and transposons, which probably explain their spread
among gram-negative genera. Thus leaving the
physician with few
therapeutic options. Klebsiella pneumoniae strains that were resistant to
all currently available antibiotics, including the polymyxins, had been
reported (Souli et al.,2008). Also of greatest concern were reports of
infections caused by organisms that were resistant to all currently
available antibiotics, including the polymyxins (Valencia et al., 2009).
Hospital-acquired pneumonia is the most common life-threatening
hospital-acquired infection, and the majority of cases are associated with
mechanical ventilation. Ventilator-associated pneumonia occurs in
approximately 10 to 20% of patients who are on ventilators for longer
than 48 hours and is associated with significant increases in length of
hospital stay, mortality, and costs (Jarvis, 2007).
Regarding
our study, gram-negative organisms predominate in
hospital-acquired pneumonia, particularly Klebsiellae spp., Enterobacter
spp., Pseudomonase
aeruginosa,
and Acinetobacter baumannii
in
descending order of frequency. On the contrary in the study of Gaynes
and
Edwards, (2005), gram-negative organisms that predominate in
hospital-acquired
pneumonia
were
Pseudomonase
aeruginosa,
Acinetobacter baumannii, and then Enterobacteriaceae.
In a recent survey in Europe, 26.4%
aeruginosa isolates
and
36.8%
of
of 679
Pseudomonase
427 Acinetobacter baumannii
isolates that caused ventilator-associated pneumonia were resistant to
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Discussion
carbapenems (imipenem or meropenem) (Hidron et al., 2008). Similar
data had been reported from other parts of the world, with countries such
as Greece reporting rates of carbapenem resistance of up to 85% among
ICU isolates (Souli et al.,2008).
In our study one Acinetobacter baumannii
strain was recovered
from a case of ventilator-associated pneumonia in surgery unit and was
resistant to meropenem but sensitive to imipenem. Another one strain
of Pseudomonase aeruginosa was recovered from sputum of ventilated
patient in adult ICU and was resistant to the whole panel of sensititer
antibiotics , one Klebsiella Oxytoca , one Raoultella terrigena and two
Klebsiella Pneumoniae were recovered from sputum samples in ICU and
were resistant to meropenem but sensitive to imipenem.
Compounding the problem of antimicrobial-drug resistance is the
immediate threat of a reduction in the discovery and development of new
antibiotics (Boucher et al., 2009). Several factors have contributed to this
decline, including the increasing challenges of screening for new
compounds, the high capital costs and long time required for drug
development, the growing complexity of designing and performing
definitive clinical trials, and the concern about reduced drug longevity
due to the emergence of resistance. As a consequence, a perfect storm has
been created with regard to these infections; increasing drug resistance in
the absence of new drug development (Peleg and Hooper, 2010).
The highest rates of nosocomial
gram
positive bacterial
infections were observed in ICUs in our hospital, which were also the
units in which the most severely ill patients were treated and the highest
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Discussion
mortality rates were observed. Similar findings were found in other
studies (Laupland et al., 2002).
We observed that the incidence of nosocomial
MRSA among
collected Staphylococcus aureus was 24.4% in contrast to the results of
Albertini
et al .,(2002) which showed higher rate .The results of
Randrianirina et al.,(2010) were much lower than in most countries.
The prevalence of MRSA varies greatly throughout the world, as a
function of site of infection and whether the infection is nosocomial or
community-based.
All our MRSA isolates were vancomycin , linezolid and
quinuprisitin / dalfopristin susceptible , but only 80% were daptomycin
susceptible .On the other hand surveillance of nosocomial infections at a
Saudi Arabian military hospital for a one-year period found that MRSA
were 98.5%
vancomycin susceptible and all CONS were vancomycin
susceptible (Abdel-Fattah , 2005 ). In the present study we recorded 3
cases of
MRCONs strains which were also vancomycin and linezolid
resistance .These VRCONS strains were recovered from blood cultures in
neonatal ICU in low birth weight immunosuppresed neonates receiving
vancomycin for approximately one month.
Vancomycin-resistant enterococcus can cause serious infections in
vulnerable, immunocompromised patients. Multiple studies have shown
that VRE spreads mainly via contaminated hands, cloths and portable
equipment carried by healthcare workers (Chlebicki and Kurup, 2008).
We isolated 3 VRE strains (two enterococcus faecium and one
enterococcum fecalis) from blood cultures in adult ICU patients, on the
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Discussion
contrary Abdel-Fattah, (2005)
did not observe resistance
to
vancomycin among isolated enterococci.
As pointed out in an extensive review by Safdar and Maki, (2002)
there is a remarkable commonality of risk factors for infection and
colonisation with several nosocomial pathogens such as VRE, MRSA,
and ESBL producing gram-negative bacteria.
Antibiotic exposure has been consistently identified as a risk factor
for VRE positivity. It facilitates VRE transmission by 2 mechanisms:
It suppresses normal competing bowel flora providing selective
advantage for VRE and it increases concentration of VRE in stool of
previously colonized patients rendering them more contagious (Donskey
et al .,2000).
VRE colonization has been associated with multiple classes of
antibiotics including glycopeptides, second and third generation of
cephalosporins and other antibiotics with prominent anti-anaerobic
activity (Donskey et al., 2000).
The results from our study provide a snapshot of the antibiotic
resistance profile of prevalent
nosocomial gram-negative bacilli and
gram positive cocci in Benha University Hospitals as it comprehensively
examined the antibiotic susceptibilities of these isolates.
In our work
a standardized dilution method was used for testing
isolates and antibiotic susceptibilities (MIC)
were interpreted using a
common standard. This method allows standardization of results across
institutions that use different susceptibility testing methods (e.g. disc
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Discussion
diffusion,
semiautomated
testing
systems*sensititer*)
and
CLSI
breakpoints for determining susceptibility.
All our Enterobacteriaceae isolates were resistant to extendedspectrum cephalosporins as a consequence of
production
and/or
carbapenemase
ESBL and/or AmpC
production. The phenotypic
methods used in our study are unable to differentiate between
chromosomally and plasmid-borne AmpC genes. The presence of these
resistance mechanisms was also associated with coresistance to other
classes of antibiotics, including the very commonly prescribed
ciprofloxacin, for which only 3 of every 10 nosocomial
gram negative
isolates remain susceptible. This high level of ciprofloxacin resistance
rules out the use of ciprofloxacin as empirical treatment when invasive
infections due to these pathogens are suspected.
Our results demonstrated that, in general, isolates have high rates
of resistance to antibiotics commonly used in developing countries. We
also found a high rate of resistance to penicillins, B lactam/B lactamase
inhibitor combinations, first and second generation cephalosporins and
trimethoprim/ sulphamethoxazole.Therefore , cheap antibiotics such as
amoxicillin, tetracyclin and trimethoprim/ sulphamethoxazole are now of
limited benefit in the treatment of infections. These results
were
probably due to overuse and misuse of broad-spectrum antibiotics
(Randrianirina et al., 2010)
Although our limited sample size, uncommon forms of resistance
were detected among uncommon pathogens that is difficult, if possible,
to be identified by conventional methods without the use of automation.
For example, the isolation of
Raoultella terrigena strain from
our sputum
was resistant to all currently available
samples. It
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one of
Discussion
antibiotics but only sensitive to imipenem. The name Raoultella is
proposed as a genus name for species of klebsiellae of cluster II. The
genus Klebsiellae is heterogeneous
and
composed of species which
form three clusters that also included members of other genera, including
Enterobacter aerogenes, Erwinia
clusters I and II and
Cluster I contained the type strains
Tatumella.
of Klebsiella pneumoniae subsp.
Pneumonia, Klebsiella pneumoniae subsp. Rhinoscleromatis
and
Klebsiella pneumoniae subsp. ozaenae. Cluster II contained Klebsiella
ornithinolytica , Klebsiella planticola , Klebsiella trevisanii and
Klebsiella terrigena. Cluster III contained
Klebsiella oxytoca
(Drancourt et al., 2001) .It was identified as an ESBL producer and this
was
consistant with the results of
Peterson et al., (2008) who
documented the appearance of multiresistant strains among clinical
Klebsiellae isolates , especially those producing ESBLs , which show
resistance to extended-spectrum cephalosporins , and their rates were
increasing over the past several years.
Also we identified 3 strains of Klebsiella group 47, isolated from
blood cultures of
neonatal ICU cases. One was identified as an only
ESBL producer, and the other 2 strains were resistant to the whole panel
of sensititer antibiogram including imipenem and meropenem and both
were identified as positive MBL producers using our imipenem-EDTA
combined discs test. Klebsiella group 47 represents a single new species
in the genus Klebsiellae for which the name Klebsiella ornithinolytica is
proposed (Sakazaki et al., 1989). Now it is considered as a species of
klebsiellae of cluster II (Drancourt et al.,2001).
We isolated a strain of Aeromonas hydrophila subsp. hydrophila
from post operative brain abscess pus after removal of a benign tumour in
surgery unit. It was highly resistant to the whole panel of sensititer
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Discussion
antibiogram including imipenem and meropenem and was identified as
ESBL producer in our ESBL and AmpC detection kit. In an analysis
of drug resistance of pathogenetic aeromonase
done by Zhao-wei and
his colleagues, (2008) they demonstrated that 4.4% were multidrug
resistant.
Warren and
his colleagues, (2000) isolated a
member of the
Enterobacteriaceae identified as Kluyvera cryocrescens by the MicroScan
Gram-Negative Combo 13 panel caused an outbreak of nosocomial
infections in four patients (2 pneumonia, 1 urinary tract infection and 1
wound infection) and urinary tract colonization in one patient . The
antibiotic susceptibility testing revealed the presence of ESBL resistance.
They concluded that Kluyvera cryocrescens appears to be a new
opportunistic pathogen that can serve as a source of ESBL resistance in
the hospital. The same finding was found in our study as we recovered a
strain of
ESBL producer Kluyvera cryocrescens from hysterectomy
wound infection. It was resistant to the whole panel of sensititer
antibiogram including meropenem but the strain was only sensitive to
imipenem.
Nosocomial infections are a major challenge to patient safety. It is
estimated that in 2002, a total of 1.7 million hospital-acquired infections
occurred (4.5 per 100 admissions), and almost 99,000 deaths resulted
from or were associated with a hospital-acquired infection , making
hospital-acquired infections the sixth leading cause of death in the United
States ; similar data have been reported from Europe. The estimated costs
to the U.S. health care budget are $5 billion to $10 billion annually.
Approximately one third or more of hospital-acquired infections are
preventable (Peleg and Hooper, 2010).
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