Healthcare Associated Infection in the Neonatal Intensive Care Unit of King Abdl Aziz Specialist Hospital , Taif , KSA

Healthcare-associated infection is a common problem of newborn in neonatal intensive care units. It results in high mortality rate and serious complications. The Aim: to assess the incidence, etiology and the mortality of healthcareassociated infections of patients in neonatal intensive care unit at King Abdl Aziz Specialist Hospital (KAASH), Taif, Kingdom of Saudi Arabia. Material and Methods: This is a retrospective study including 8033 neonates admitted to neonatal intensive care unit during period between April, 2006 and December, 2012. The health-care associated infection rate, mortality rate, causative organism and risk factors were studied. Results: The prevalence of health-care associated infection was found to be 6.03%; the mortality rate was 27.1%. The highest prevalence was among children with the birth weight below 1000 g. The most frequent causative pathogen was klebseilla spp, followed by other gram negative bacilli. Conclusion: The rate of healthcare-associated infections in neonatal intensive care unit at KAASH was relatively high. In addition, the mortality rate was observed to be high (27.1%) owing to the high virulence of the causative organisms.


Introduction
Health-care associated infections (HAIs) continue to be a major public health problem throughout the world, especially in the neonatal intensive care unit (NICU).Neonates in the NICU are a very vulnerable group due to defective immunity and the increasing number of technology dependant infants [1,2].Deficiencies of both innate and adaptive immunity contribute to the impaired neonatal host defense [3].A domination of naive immune cells, functional impairments and lower leukocyte subset numbers contribute further to an increased susceptibility [4,5].The mode of infection transmission is mainly through the care-giver staff specially if the proper antiseptic measures are not considered [4].Infection control for preventing nosocomial infections may play an important role in reducing medical costs, period of hospital stay, and mortality in hospitalized patients [6].
Sepsis in the newborn is classified into early-onset form (EONS), within the first 72 hours of life, and lateonset form (LONS), which takes place afterwards (3).HAI in the NICU takes many forms, and the most frequent forms are the blood stream infection (septicemia) (28%), ventilator associated pneumonia (21%).Meningitis, gastro-enteritis, skin and eye infections are also common infections [7].Many risk factors of HAI in the NICU are involved.The most important is excessive invasive procedures such as peripheral cannulation, central venous catheter placement, tracheal incubation and ventilation [6].Furthermore, the duration of hospital stay, plays an important role; that is, the longer the stay, the higher the incidence of HAI [7].Premature infants, with a birth weight less than 1000 g (ELBW: extremely low birth weight infants), are particularly predisposed to sepsis, as there is an inverse correlation between gestational age, birth weight, and sepsis [8,9].Furthermore, the age of the neonate has a role in the incidence of HAI.Previous stu-Healthcare Associated Infection in the Neonatal Intensive Care Unit of King Abdl Aziz Specialist Hospital, Taif, KSA 301 dies have shown that the peak incidence of infection occurred between the age of 10 th and 20 th day [2].Many organisms are involved in neonatal HAI, and the commonest are E. coli (36.6%),Staphylococcusaureus (29.5%),Pseudomonas spp (22.4%),Klebsiella spp (7.6%) and Proteus spp (3.8%).St pneumoniae, enterococci and Serratia are also involved [10,11].In spite of the high prevalence and severity of neonatal HAI, the hospital represents a well established reservoir for resistant organisms that makes the problem difficult to control, and neonatal HAI is still a preventable problem, as risk factors can potentially be employed to develop local strategy for prevention [12].This could be achieved through strict antiseptic measures for environment, staff, equipment, and minimizing invasive procedures [13].These perfect control measures require proper epidemiological studies and tracing of infection [14].The principal method of diagnosing sepsis is the isolation of causative organisms from blood cultures and antimicrobial susceptibility testing [15,16].Results are usually available between 48 -72 hours after specimen collection and therefore, initial antimicrobial treatment has been usually empirical with the aim that the most likely pathogens would be susceptible to the chosen drugs [15].Therefore, this study was conducted in order to investigate the epidemiological characteristics of HAI in the aspects of infection rate, common pathogens and risk factors in our NICU in order to guide empirical therapy and improve better preventive measures.

Clinical Setting and Patients Population
This is a retrospective, hospital-based study.It was carried out in the neonatal intensive care unit (NICU) at King Abdul Aziz Specialist Hospital (KAASH), Taif, Kingdom of Saudi Arabia during the period April 2006 -December, 2012.KAASH is a 500-bed tertiary-level hospital.The NICU is a level III nursery with 60 bed capacity, dealing with all cases delivered in the hospital that ranges between 12,000 to 14,000 deliveries each year.Data were collected from the medical records in standardized collection sheets and included demographic data, birth weight, gestational age, gender, outcome, and delivery data (mode of delivery, maturity).The prevalence of sepsis was calculated by dividing the number of newborns with sepsis by the total number of newborns admitted to the NICU.

Case Definition
Health care associated sepsis, defined as a positive blood culture taken after 48 hours of admission to NICU with presence of clinical signs that are suggestive of neonatal septicemia [12].

Culture and Susceptibility
Each neonate showing manifestation of sepsis was subjected to sampling for blood culture, cerebrospinal fluid (CSF) culture, or other samples according the clinical presentation.Blood culture was done for all neonates who were suspected to have sepsis.All blood samples were collected from the peripheral vein under strict aseptic precautions, before starting antibiotic therapy.Blood culture samples were incubated in the BacT/ALERT 3D (bioMerieux, France), sub-cultures were done on blood agar, chocolate agar, Mannitol salt agar and Mac Conkey's agar plates (Oxoid) and incubated at 37˚C for 24 -48 hours.The bacterial isolates were identified by standard laboratory techniques, using standard culture media and biochemical reactions according to the Clinical Laboratory Standard Institute (CLSI) criteria.Thereafter, antibiotic susceptibility testing was performed on Muller Hinton agar (Oxoid) by Kirby-Bauer disk diffusion method and interpreted according to CLSI criteria [17].Data were analyzed using SPSS software (Version 10.0; SPSS Inc., Chicago).

Results
Table 1 shows that during the study period (April, 2006-December, 2012) the total number of the patients admitted to the neonatal intensive care unit were 8033 neonates.The total HAI rate in our ICU was 6.03%.Being highest in year 2006 followed by year 2007.While was lowest in year 2008.There were a total 484 health care associated infections, of them 258 infant were males and 226 were females.
The studied newborn were categorized acceding to the birth weight into four groups group I (less than 1000 g), group II (1000 -1500 g), group III (1501 -2500 g) and group IV (more than 2500 g).
The results showed different HAI rate among four birth weight groups.The highest rate (29.54%) was found in patients with weight below 1000 g, and was 26.65% in group II, 28.7% in group III while, the HAI rate among the fourth group was only 14% (Table 2).
Also, the studied newborn were categorized acceding to the gestational age in weeks into four groups group I (less than 28 w), group II (28 -31 w + 6 days), group III (32 -36 w + 6 days) and group IV (equal or more than 37 w) (Table 2).During the study period, the most common recovered organism was klebseilla spp (128 isolates) followed by Enterobacter spp species, E. coli and Acinetobacterspp (79, 78 and 72 isolates respectively.Whereas gram positive cocci as CoNS, Staphylococcus aureus and Enterococcus were less frequent (31, 9, and 7 isolates respectively) (Table 3).The most common organism associated with complication was klebseilla spp (128 total complication) whereas death was the most frequent complication where 131 case of death were reported.Resistance to amoxicillin was the highest as it was observed in 90% of Klebsiella and 81% of E. coli, whilst other Gram negative bacilli showed complete resistance to this drug.Klebsiella and E. coli also exhibited increased resistance to gentamycin (60% and 57% respectively), as well as to Cipro-floxacin

Discussion
Health care associated infections in the NICU constitute a major health problem and may be associated with substantial morbidity and mortality.Those infections in neonates are life-threatening emergencies.Identification of the common bacteria causing such infections and their susceptibility patterns will provide necessary information for timely intervention [18].In the present study, the collective HAI rate in our NICU over years 2006-2012 was 6.03%.but generally the infection rate had declined in our NICU (Table 2).The results of the present study are in agreement with previous study reported by Iwona et al., (2012) over the 6-year period, from 2005 to 2010, in which 2610 neonates were hospitalized in NICU and HAI was 7.32% [19].Furthermore, a retrospective study done in the neonatal intensive care unit of the Mexican institute in the period between 2004 and 2007, HAI was found 4.3% (514 out of 11,790 newborns) [20].However, on the other hand, a similar study conducted in Nigeria estimated HAI rate in university of Port Harcourt Teaching Hospital was 34.2%, [21,22].Also in Korea, Jeong et al., [23] reported a HAI rate in NICU of 30.3% [24].This variability in HAI rate depends besides infection control measure on many determinant factors such as the gestational age, birth weight distribution of the infants surveyed for the report, and on the specific environment and care practices, [23].
In the present study, HAI rate differs among four birth weight groups.The highest rate (29.54%) was found in patients with weight below 1000 g.However it was surprising that the HAI rate was the higher in group III (1501 -2500 g) than in group II (100 -1500 g) which was found to be 28.7% and 26.65% respectively, while, the HAI rate among the fourth group was only 14%.With regards to the effect of gestational age on HAI in the present study was in line with that of birth weight (the highest in newborn less than 28 weeks), this may be related to fact that low birth weight and premature labor mostly occur in combination.The majority of investigators have indicated that the risk of developing HAI increased with lower birth weight.Stoll et al., [3] reported infection rates of 50% for infants weighting below 750 g, 33% for those between 751 and 1000 g, 21% for those between 1001 and 1250 g and 10% for those between 1251 and 1500 g [3].During the study period, the most common pathogen incriminated for health care-associated infection was klebseilla spp (128 isolates) followed by Enterobacter spp species, E coli and Acinetobacter spp (79, 78 and 72 isolates respectively), which means that Gram negative bacilli were the major causative pathogen in our NICU.The same findings were reported by Yilmaz et al., [25] where Klebsiella spp.And E. coli, together, were responsible for 67% of HAI occurred in NICU [25].Many investigators concur with our study in reporting that Gram-negative rods as the most common etiological factors [26].Whereas, Gaynes et al., [27] and Stoll et al., [3], differ as they found that co-agulase-negative staphylococci were the most common pathogen, presenting in 51% and 55% of cases, respectively [3,27].The similar observation had Yelda et al., [20], they found that Gram-positive cocci account for 55.4% of HAI, and the most common organisms were Staphylococci [20].
Most of these isolates showed multiple antibiotics resistance.Results showed that approximately one-third of Klebsiella species (42/128) and E. coli (26/78) were ESBL producers .These results are in agreement with Dinesh et al., (2011) who described a widespread problem of ESBL-producing multidrug-resistant strains of Klebsiella and E. coli in hospital [28].Also Amita et al., (2003) reported that more than 78% of Gram-negative isolates were positive in the screening test for ESBL production in blood borne neonatal infections [29].
The mortality rate was relatively high in the present study (27%); since all fatality cases were associated with Gram-negative pathogens.Gram-negative HAI often presents with a more rapid clinical deterioration and is commonly associated with shock and coagulation problems.According to Makhoul et al., [30] mortality after Gramnegative sepsis (26.2%) and Candida sepsis (27.6%) is similar and significantly higher than with Gram-positive sepsis (8.7%) [30].Although other authors show that mortality caused by Gram positive pathogens is lower, about 2.83% to 6.98% [31].However, organisms like co-agulase-negative Staphylococci may be underestimated because many cultures that grow Gram-positive bacteria represent skin contaminants rather than true blood stream infections.

Open Access AID
Healthcare Associated Infection in the Neonatal Intensive Care Unit of King Abdl Aziz Specialist Hospital, Taif, KSA 304

Conclusion
The overall HAI rate in our NICU over years 2006 -2012 was relatively high although declining in the recent years due to application of strict infection control measures, and the most prevalent organism was klebseilla spp, followed by other gram negative bacilli which commonly associated with shock and coagulation problems.Therefore, these organisms are blamed for relatively high mortality rate.