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Asian Pac J Trop Biomed 2015; 5(7): 509–514 509

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Contents lists available at ScienceDirect

Asian Pacific Journal of Tropical Biomedicine


journal homepage: www.elsevier.com/locate/apjtb

Review article http://dx.doi.org/10.1016/j.apjtb.2015.05.001

Nosocomial infections and their control strategies

Hassan Ahmed Khan1, Aftab Ahmad2, Riffat Mehboob3,4,a*


1
University of Lahore, Lahore, Pakistan
2
National Academy of Young Scientists (NAYS), University of the Punjab, Lahore, Pakistan
3
Department of Biomedical Sciences, King Edward Medical University, Lahore, Pakistan
4
Department of Neuroscience, SISSA, Trieste, Italy

A R TI C L E I N F O ABSTRACT

Article history: Nosocomial infections are also known as hospital-acquired/associated infections. Na-
Received 9 Mar 2015 tional Healthcare Safety Network along with Centers for Disease Control for surveillance
Received in revised form 30 Mar has classified nosocomial infection sites into 13 types with 50 infection sites, which are
2015 specific on the basis of biological and clinical criteria. The agents that are usually
Accepted 26 Apr 2015 involved in hospital-acquired infections include Streptococcus spp., Acinetobacter spp.,
Available online 16 June 2015 enterococci, Pseudomonas aeruginosa, coagulase-negative staphylococci, Staphylo-
coccus aureus, Bacillus cereus, Legionella and Enterobacteriaceae family members,
namely, Proteus mirablis, Klebsiella pneumonia, Escherichia coli, Serratia marcescens.
Keywords:
Nosocomial pathogens can be transmitted through person to person, environment or
Hospital-acquired infection
contaminated water and food, infected individuals, contaminated healthcare personnel's
Antibiotics
skin or contact via shared items and surfaces. Mainly, multi-drug-resistant nosocomial
Control strategies
organisms include methicillin-resistant Staphylococcus aureus, vancomycin-resistant
Surveillance
enterococci, Pseudomonas aeruginosa and Klebsiella pneumonia, whereas Clostridium
difficile shows natural resistance. Excessive and improper use of broad-spectrum anti-
biotics, especially in healthcare settings, is elevating nosocomial infections, which not
only becomes a big health care problem but also causes great economic and production
loss in the community. Nosocomial infections can be controlled by measuring and
comparing the infection rates within healthcare settings and sticking to the best healthcare
practices. Centers for Disease Control and Prevention provides the methodology for
surveillance of nosocomial infections along with investigation of major outbreaks. By
means of this surveillance, hospitals can devise a strategy comprising of infection control
practices.

1. Introduction countries [3]. Asymptomatic patients may be considered


infected if these pathogens are found in the body fluids or at a
“Nosocomial” term is used for any disease acquired by pa- sterile body site, such as blood or cerebrospinal fluid [4].
tient under medical care [1]. It is an infection acquired by patient Infections that are acquired by hospital staff, visitors or other
during hospital stay. Recently, a new term, “healthcare healthcare personnel may also be considered as nosocomial [5].
associated infections” is used for the type of infections caused The situations in which infections are not believed as noso-
by prolonged hospital stay and it accounts for a major risk comial are: (1) The infections that were present at the time of
factor for serious health issues leading to death [2]. About 75% admission and become complicated, nevertheless pathogens or
of the burden of these infections is present in developing symptoms change resulting to a new infection; (2) The in-
fections that are acquired trans-placentally due to some diseases
like toxoplasmosis, rubella, syphilis or cytomegalovirus and
*Corresponding author: Dr. Riffat Mehboob, Department of Biomedical appear 48 h after birth [6].
Sciences, King Edward Medical University, Lahore, Pakistan. Hospital-acquired infections appeared before the origination
E-mail: [email protected]
Peer review under responsibility of Hainan Medical University. of hospitals and became a health problem during the miraculous
a
Present address: Neurobiology sector, SISSA, Trieste, Italy. antibiotic era. Due to these infections, not only the costs but also

2221-1691/Copyright © 2015 Hainan Medical University. Production and hosting by Elsevier (Singapore) Pte Ltd. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
510 Hassan Ahmed Khan et al./Asian Pac J Trop Biomed 2015; 5(7): 509–514

the use of antibiotics increased with an extended hospitalization. nosocomial infections in the 1960s, but from 1975 to 1980s,
This resulted in elevated morbidity and mortality. Studies con- Acinetobacter spp. with P. aeruginosa created clinical diffi-
ducted in different parts of the world show that in North culties [12]. During the recent years, streptococci along with
America and Europe 5%–10% of all hospitalizations result in coagulase-negative staphylococci and coagulase-positive staph-
nosocomial infections, while Latin America, Sub-Saharan Africa ylococci reemerged and incidence level of K. pneumonia and
and Asia show more than 40% hospitalizations with nosocomial E. coli declined from 7% to 5% and 23%–16%, respectively [13].
infections [7].
Nosocomial infections can be caused by any organisms but 4. Bacteriology of commonly isolated nosocomial
few organisms are particularly responsible for hospital-acquired pathogens
infections. In this review article, a brief overview on different
aspects of nosocomial infections, particularly sites of infections, A multicenter study was conducted in Japan to isolate bac-
common nosocomial bacterial agents, selected antibiotic- teria from surgical infections during 2011–2012. About 785
resistant pathogens along with their modes of transmission and strains including 31 of Candida spp. were isolated from 204 out
control measures will be discussed. of 259 surgical patients. About 523 strains were isolated from
primary infections and 231 from surgical site infection. From
2. Types of nosocomial infections primary infections, anaerobic Gram-negative bacteria were
prevalent. Enterococcus spp. was the highest among Gram-
National Healthcare Safety Network with Center for Disease positive aerobic bacteria followed by Streptococcus and Staph-
Control (CDC) for surveillance has classified nosocomial infec- ylococcus spp. E. coli was the predominant form among the
tion sites into 13 types, with 50 infection sites, which are specific Gram-negative aerobic bacteria followed by K. pneumonia,
on the basis of biological a nd clinical criteria. The sites which are P. aeruginosa and Enterobacter cloacae [14].
common include urinary tract infections (UTI), surgical and soft
tissue infections, gastroenteritis, meningitis and respiratory in- 4.1. S. aureus
fections [8]. A change regarding nosocomial infection sites can be
easily detected with time due to the elevated use of cancer Out of many species of Staphylococcus genus, S. aureus is
chemotherapy, advancement in organ transplantation, considered one of the most important pathogens, responsible for
immunotherapy and invasive techniques for diagnostic and nosocomial infections. It is Gram-positive cocci, non-spore
therapeutic purposes. The perfect example of this can be seen in forming, catalase- and coagulase-positive, immotile, faculta-
the case of pneumonia as prevalence of nosocomial pneumonia tively anaerobe [15]. It is not only a disease-causing organism but
increased from 17% to 30% during five years [9]. also plays its role as commensal. It mainly colonizes in nasal
passages. About 20% individuals have persistent colonization of
3. Agents of nosocomial infections S. aureus, whereas 30% are intermittent. Hospitalized patients
with decreased immunity and immunocompetent people in
Nosocomial infections are caused by many microbes and each community are more prone to S. aureus infections. S. aureus
one can cause infection in healthcare settings. Bacteria are infects not only the superficial but also the deep tissues and local
responsible for about ninety percent infections, whereas pro- abscess lesion. Toxin-mediated diseases of S. aureus include
tozoans, fungi, viruses and mycobacteria are less contributing food poisoning, due to ingestion of enterotoxins, while toxic
compared to bacterial infections [10]. The agents that are usually shock syndrome toxin 1 is responsible for toxic shock syndrome
involved in hospital-acquired infections include Streptococcus [16] and exfoliative toxins cause staphylococcal scalded skin
spp., Acinetobacter spp., enterococci, Pseudomonas aeruginosa syndrome. Virulence mechanisms of S. aureus include toxins,
(P. aeruginosa), coagulase-negative staphylococci, Staphylo- enzymes and immune modulators [15].
coccus aureus (S. aureus), Bacillus cereus (B. cereus), Legionella
and Enterobacteriaceae family members including Proteus mira- 4.2. E. coli
blis, Klebsiella pneumonia (K. pneumonia), Escherichia coli
(E. coli), Serratia marcescens. Out of these enterococci, E. coli is an emerging nosocomial pathogen causing prob-
P. aeruginosa, S. aureus and E. coli have a major role [11]. UTI lems in health care settings [17]. E. coli is Gram-negative and
usually contain E. coli, while it is uncommon in other infection oxidase-negative facultative anaerobe bacteria. It can colonize in
sites. Contrarily, S. aureus is frequent at other body sites and gastrointestinal tract of human beings and other animals. E. coli
rarely causes UTI. In blood-borne infections, coagulase-negative is responsible for a number of diseases including UTI, septi-
S. aureus is the main causative agent. Surgical-site infections cemia, pneumonia, neonatal meningitis, peritonitis and gastro-
contain Enterococcus spp. which is less prevalent at respiratory enteritis. Virulence factors meant for its pathogenicity are
tract. One tenth of all infections are caused by P. aeruginosa, endotoxins, capsule, adhesions and type 3 secretion systems [18].
which is evenly distributed to the entire body sites [4]. Specialized virulence factors are seen in case of UTI and
Excessive and improper use of broad-spectrum antibiotics, gastroenteritis.
especially in healthcare settings, are elevating nosocomial in-
fections. Penicillin-resistant pneumococci, multi-drug-resistant 4.3. Vancomycin-resistant enterococci
tuberculosis, methicillin-resistant S. aureus (MRSA),
vancomycin-resistant S. aureus are common examples of drug- Enterococci is the second leading cause of hospital acquired
resistant bacteria. The distribution of bacteria in nosocomial infections worldwide and the main leading cause in United
infections is changing over time. For example, Proteus spp., States contributing 20%–30% of infections. These are facultative
Klebsiella spp. and Escherichia spp. were responsible for anaerobic Gram-positive enteric microbes [19]. They are a part of
Hassan Ahmed Khan et al./Asian Pac J Trop Biomed 2015; 5(7): 509–514 511

normal microbiota in female genital tract and gastrointestinal or weeks and become a source of contamination for healthcare
tract as well. Enterococci are involved in the blood-borne in- individuals and other patients [21].
fections; UTI and wound infections consort to surgical pro-
cedures [20]. Virulence factors include extracellular surface 5.4. K. pneumonia
proteins, cytolysin, adhesions, hemolysins, gelatinase,
extracellular superoxide and aggregation substances [21]. In hospital settings, K. pneumonia can be transmitted by
person-to-person contact and especially when healthcare pro-
4.4. K. pneumonia fessionals do not wash or clean hands after checking a
contaminated patient. Respiratory machines, catheters or
Three to seven percent of hospital-acquired bacterial in- exposed wounds can be the source of its transmission.
fections are related to K. pneumonia, which is the eighth sig- K. pneumoniae is reported to be transmitted through stool
nificant pathogen in healthcare settings. It is a Gram-positive (77%), patients’ hands (42%) and pharynx (19%) [22].
bacillus and an opportunistic bacterium, which is a part of
Enterobacteriaceae family. It usually colonizes gastrointestinal 5.5. P. aeruginosa
tract, pharynx and skin. It gets involved in diseases such as
neonatal septicaemia, pneumonia, wound infections and septi- Common reservoirs for its contamination include breast
cemia. Its virulence factors include endotoxins, cell wall re- pumps, incubators [26], sinks and hands of hospital staff and
ceptors and capsular polysaccharide [22]. hand soaps [27].

4.5. P. aeruginosa 5.6. C. difficile

P. aeruginosa contributes to 11% of all nosocomial in- Spores of C. difficile can hold for months and become a
fections, which result in high mortality and morbidity rates. It is problem for disinfectants and cleaning agents. Inanimate objects
non-fermenter Gram-negative organism causing diseases espe- and infected intestinal patients are major sites acted as reser-
cially among immune-compromised people. The sites of colo- voirs. Hospital staff along with hospital settings are also playing
nization are kidney, urinary tract and upper respiratory tract. It is their part to a greater extent [28].
a cause of surgical and wound infections, UTI, pneumonia,
cystic fibrosis and bacteremia. Some of important virulence 6. Selected antibiotic-resistant nosocomial pathogens
factors are adhesions, hemolysins, exotoxins, proteases and
siderophores [23]. Multi-drug-resistant nosocomial organisms include MRSA,
vancomycin-resistant enterococci, P. aeruginosa and
4.6. Clostridium difficile (C. difficile) K. pneumonia, whereas C. difficile shows natural resistance. In
the 1940s, the problem of drug resistance came into light and in
C. difficile is an important nosocomial pathogen which the past few years, a rapid increase of multi-drug-resistant
mainly causes diarrhea. Several cases of C. difficile are reported pathogens was seen.
in Europe, U.S. and Canada. It is a Gram-positive bacillus. It is Fifty to sixty percent of hospital-acquired infections are
anaerobic and spore-forming bacteria. It usually colonizes in caused by resistant pathogens in the United States. Improper use
intestinal tract and serves as part of normal microbiota [24]. of antibiotics is thought to be the major cause of this drug
Diseases caused by toxins produced by C. difficile are colitis resistance.
and it is responsible for 15%–25% cases of diarrhea. Major
virulence factors for C. difficile are toxins, fimbriae, capsule 6.1. MRSA
and hydrolytic enzymes [25].
b-Lactamase antibiotics including penicillin along with other
5. Modes of transmission antimicrobials became resistant in the 1940s. Resistance of
penicillin slowly prevails from hospitals to community due to its
5.1. S. aureus improper use. This resistance results are due to the Staphylo-
coccal species having penicillinase enzyme which was later
Transmission of S. aureus is through infected individuals’ solved by the introduction of penicillinase-resistant antibiotics,
skin or contact via shared items and surfaces like door handles, cephalosporins. In the 1960s, methicillin-resistant species of
benches, towels and taps. S. aureus were reported. This resistance was due to the modi-
fication of penicillin-binding proteins. This modification made
5.2. E. coli all b-lactam antibiotics along with their derivatives ineffective.
Aminoglycosides resistance was another addition to methicillin
E. coli can be transmitted through person to person, envi- resistance [29].
ronment or contaminated water and food [17].
6.2. Vancomycin-resistant enterococci
5.3. Vancomycin-resistant enterococci
Vancomycin resistance is seen in the enterococcal species
Patients with diarrhea are common means of transmission. due to the vanA and vanB genes. These genes are a part of
Their room items such as surfaces and equipments act as res- plasmid and would spread resistance to other microbes as well.
ervoirs. This bacterium can survive on theses surfaces for days Enterococci are resistant to different classes of antibiotics which
512 Hassan Ahmed Khan et al./Asian Pac J Trop Biomed 2015; 5(7): 509–514

include penicillin, ampicillin, aminoglycosides, tetracyclines, 7. Control of nosocomial infections


carbapenems, fluoroquinolones and macrolides [30].
There is a lack of actual statistics regarding the causes and
6.3. P. aeruginosa antimicrobial susceptibility in developing countries. Pathogens
with resistant organisms make it extremely difficult to devise a
P. aeruginosa is becoming resistant due to different mecha- proper plan and its implementation for control [3].
nisms working against antibiotics. These mechanisms include
the restricted uptake of drug, drug modification and altered 7.1. Measurement and comparison of infection rates
targets for antibiotics. Due to this increasing resistance, com-
plications are seen in the treatment of P. aeruginosa infections. It is difficult to measure the infection rates in different
The drugs that are now ineffective due to increasing resistance healthcare settings. For the measurement of infection rates, it is
include cephalosporins, trimethoprim, macrolides, chloram- important to know the types of microorganism involved and its
phenicol, tetracyclines and fluoroquinolones [23]. correct location inside the body of individual. Infectious or-
ganisms are heterogeneous in nature, which makes them
6.4. K. pneumonia different from one another. It is possible that in a hospital, the
rates of infection show similarity while the location and het-
Resistance to b-lactam antibiotics is a major cause of com- erogeneity of organisms greatly differ.
plications in nosocomial infections. K. pneumonia is one of the To compare the infection rates, one must know the type of
microbes experiencing resistance of b-lactamase antibiotics healthcare settings, which may be public or private, because the
along with E. coli. Cephalosporins of third and fourth generation infection rates vary in both types of hospitals. In addition, in
show resistance for K. pneumonia [22]. these hospitals, the management of infections differs greatly.
The types of services that a hospital provides to patients must be
6.5. C. difficile taken into account (Figure 1).

Increased use of broad-spectrum antibiotics against 7.2. Development of infection control programs
C. difficile-associated diseases makes it resistant. Cephalospo-
rins, fluoroquinolones, clindamycins and ampicillins are those Guidelines for the sterilization and disinfection of invasive
antimicrobials that are usually employed for C. difficile-associ- devices and medical instruments used for surgeries were
ated diseases. Recent studies reported that the improper antibi- developed as the infection rates tend to raise [31,32]. Moreover,
otic use was the cause of increasing infections of C. difficile [28]. guidelines for the prevention of catheter-associated UTI were

Figure 1. Measurement and comparison of infection rates.


Hassan Ahmed Khan et al./Asian Pac J Trop Biomed 2015; 5(7): 509–514 513

Figure 2. Suggested integrated team work for surveillance of nosocomial infections in any hospital.

also devised in 2009 [33]. Lack of compliance with the (Figure 2), hospitals can devise a strategy comprising of
guidelines, leads to the transmission of nosocomial infections. infection control practices [29].
CDC provides the methodology for surveillance of nosocomial
infections along with investigation of major outbreaks. 8. Conclusions
Infection prevention and control guidelines have been
developed but the implementation is not yet much known [34]. In the age of antibiotics, nosocomial infections are still un-
Training of healthcare professionals, especially nurses, is controllable. The control of organisms responsible for nosoco-
extremely important for the control and prevention of infection mial infections is much needed as they cause great economic as
[2,35]. A large gap is present between the existence of well as production loss. The transmission of these infections in
guidelines and their actual implementation [36]. the hospital settings through healthcare workers can be avoided
by the use of infection control practices. Improper and frequent
7.3. Surveillance of nosocomial infections use of antibiotics is an important cause of drug-resistant or-
ganisms that are difficult to treat. Hospitals should devise the
Surveillance can be interpreted as “the ongoing, systematic infection control programs through which infection rates can be
collection, analysis, and interpretation of health data essential to compared and controlled. A well-managed surveillance meth-
the planning, implementation and evaluation of public health odology is required in the light of CDC guidelines. In addition,
practice, closely integrated with the timely dissemination of there is also great need that the best practice should be shared
these data to those who need to know” [37]. As a part of among hospitals to stop the spread of nosocomial infections.
infection control program, surveillance obliges the data related
to infected individuals with their infection sites. Hospitals can Conflict of interest
work on this data to control the infections by evaluating the
efficacy of treatment. By means of this surveillance We declare no conflict of interest.
514 Hassan Ahmed Khan et al./Asian Pac J Trop Biomed 2015; 5(7): 509–514

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