Epidemiology of Serratia Marcescens in the Neonatal ICU of A Tertiary Hospital in Oman over a 10 Years Period

Muna AL Mahrooqi*, Zaina AL Maskari, Sachin Jose and Amal AL Tai

Royal Hospital, Oman *Corresponding author: Zaina Al Maskari, Royal Hospital, Oman, Email: zainamaskri2000@ gmail.com

Introduction

Healthcare-associated infections (HAIs) are among the leading causes of mortalities, morbidities, and prolonged hospital stay, resulting in considerable associated economic patient care costs. Serratia marcescens is a gram-negative bacterium described as a significant nosocomial organism that can rapidly spread, particularly in neonatal intensive care units (NICUs). The third highest number of published outbreaks is due to S. marcescens, after Klebsiella spp. and S. aureus [1]. Several S. marcescens outbreaks in NICUs were described as causing fatal meningitis, sepsis or pneumonitis in premature or low birth weight neonates with a high mortality rate of 44% which is much higher than mortality rate caused by Enterobacter cloacae, another pathogen well- known to cause disease and death in premature neonates [2].

This bacterium can be transmitted to neonates via feeding, contaminated breast pumps and antiseptics, and it can spread through contact with patients [3]. Contaminated baby shampoo was identified as the source of the outbreak in the King Abdulaziz University Hospital in Saudi Arabia. Withdrawal of the shampoo product led to the termination of the outbreak [4].

The primary objectives were to describe the Outcome (30 days mortality & length of hospital stay) of S. marcescens infection in the NICU and the determinants of mortality among infected patients. The secondary objectives were to estimate the incidence of S. marcescens infection/colonization in the NICU at Royal hospital and to study the risk factors for acquisition and the microbiology of S. marcescens strains.

Method

Setting, study designs a retrospective case-control study in the NICU of Royal Hospital, Sultanate of Oman, from 2009 to 2018. The Royal Hospital is a tertiary hospital that provides inpatient and outpatient health care services to the country. The NICU has 35 beds, 16 of which were assigned for critical cases. The unit has no active S. marcescens screening; however, at the time of outbreaks, active screening surveillance is implemented till the outbreak is controlled.

Result

A total of 93 cases had a positive culture of S. marcescens in neonates hospitalized in the NICU during the study period, and 201 controls were included. 50.5% (n=47) of cases were male and 49.5% (n=46) were females. The annual incidence proportion fluctuated from the highest incidence of 2.23 per

100 admissions in 2009 to the lowest incidence of 0.21 per 100 admissions in 2011. The incidence density per 1000 patients’ days ranged between 2.07 and 0.23, as shown in Figure 1.

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During the study period, there were a total of 36 neonatal deaths among cases and controls. The overall mortality was higher among infected patients, 17.2% (n=16) vs 10.0% (n=20) in the control group. The median time from detection of S. marcescens to discharge from the hospital is 22 (range 8.25 to 41) days. Regarding predictors of mortality from S. Variable Serratia marcescens p-value Gender Birth weight <1.5 kg 61 (30.5) 42 (46.7) Gestational age marcescens infection, univariate analysis showed that female gender (P=0.030) and mechanical ventilation (P= 0.025) were significant, and in multivariate analysis, only female gender was significant ((OR= 6.741, 95% CI= 1.307-34.767, P= 0.023) as shown in Table 1.

Adjusted Odds Ratio (OR)

$$ \begin{array}{l l l l l l l} \text {Serratia marcescens} & & \text {p - value} & \text {Adjusted Odds Ratio (OR)} & \text {95% CI for OR} & \text {P - value} \\ \text {Negative (n=201)} & \text {Positive (n=93)} & & \text {Lower} & \text {Upper} & \end{array} $$ Male (Reference) 119 (59.5) 47 (50.5) 0.165 1.02 3.801 0.044* Female 81 (40.5) 46 (49.5) 1.969

0.011* 1.498 0.634 3.54 0.357 ≥1.5 kg (Reference) 139 (69.5) 48 (53.3)

Statistically significant Table 1: Univariate and multivariate analysis to determine the independent predictors of Serratia marcescens infection.

There were significant differences between cases and controls for the acquisition of S. marcescens in birth weight (46.7% of those who had S. marcescens had a birth weight < 1.5 kg (P=0.001), premature births (P= 0.002) and born by cesarean section (P=0.0001) and had a central line (P=0.0001). All types of feeding were significant, and exposure to antibiotics was also significant (P=0.010), as shown in (Table 2). At the time of infection, 28.7% of infants were mechanically ventilated, > 50% received Total parenteral nutrition (TPN) and (21.7%) had a central venous catheter.

<1.5 kg 33 (78.6) 9 (21.4) 0.422 0.761 0.1 5.779 0.791 ≥1.5 kg (Reference) 41 (85.4) 7 (14.6) Gestational age Term birth (Reference) 21 (84.0) 4 (16.0) 1 Premature birth 55 (82.1) 12 (17.9) 0.872 0.083 9.179 0.909 Mode of delivery Vaginal Delivery (Reference) 21 (80.8) 5 (19.2) 0.757 Cesarean-section 54 (84.4) 10 (15.6) 1.156 0.223 6.003 0.863 Catheter No (Reference) 66 (83.5) 13 (16.5) 0.703 Yes 11 (78.6) 3 (21.4) 2.553 0.261 24.921 0.42 Central line Yes (Reference) 26 (78.8) 7 (21.2) 0.567 No 51 (85.0) 9 (15.0) 1.252 0.216 7.266 0.802 Procedures Yes (Reference) 55 (78.6) 15 (21.4) 0.107 No 22 (95.7) 1 (4.3) 0.339 0.029 3.989 0.39 Mechanical ventilation Yes (Reference) 44 (75.9) 14 (24.1) 0.025* No 33 (94.3) 2 (5.7) 0.172 0.024 1.219 0.078 Type of feeding Total Parenteral Nutrition TPN (Reference) 13 (72.2) 5 (27.8) Variable Mortality

p-value Adjusted Odds

$$ \begin{array}{l l l l l l l} \text {Variable} & \text {Mortality} & \text {p - value} & \text {Adjusted Odds Ratio (OR)} & \text {95% CI for OR} & \text {P - value} \\ & \text {No (n= 77)} & \text {Yes (n= 16)} & \text {Lower} & \text {Upper} \\ \text {Gender} & & & & & \\ \text {Male (Reference)} & 4 3 (9 1. 5) & 4 (8. 5) & \text {0.030} ^ {*} & & \\ \text {Female} & 3 4 (7 3. 9) & 1 2 (2 6. 1) & 6. 7 4 1 & 1. 3 0 7 & 3 4. 7 6 7 \\ \text {Birth weight} & & & & & \\ \end{array} $$ Enteral 30 (81.1) 7 (18.9) 1.146 0.159 8.235 0.892 Breast Milk (BM) 15 (93.8) 1 (6.3) 0.28 0.02 3.998 0.348 Nil Per Os (NPO) 7 (87.5) 1 (12.5) 0.391 0.028 5.509 0.486 TPN + Enteral 5 (100) 0 (0) NE TPN + BM 7 (77.8) 2 (22.2) 0.642 0.074 5.595 0.688 Surgery No (Reference) 50 (82.0) 11 (18.0) 1 Yes 27 (84.4) 5 (15.6) 0.389 0.056 2.71 0.341 Antibiotics Received (Reference) 74 (82.2) 16 (17.8) 1 Not received 3 (100) 0 (0) NE

0.394 *Statistically significant, NE - Not estimated due to non-occurrence of event. Table 2: Univariate and multivariate analysis to determine the independent predictors of mortality among Serratia marcescens infected patients.

Multivariate analysis showed that gender (female neonates, OR= 1.969, 95% CI= 1.020-3.801, P= 0.044), premature birth ((OR= 2.670, 95% CI= 1.156-6.167, P= 0.021). C-section (OR= 3.238, 95% CI= 1.591-6.591, P=

0.001); were independent factors for Serratia acquisition. Regarding the type of feeding, Enteral has four times increased risk of getting Serratia marcescens compared to TPN (OR= 3.993, 95% CI= 1.599-9.968, P= 0.003), whereas BM (OR= 4.730, 95% CI= 1.512-14.799, P= 0.008) and NPO (OR= 4.777, 95% CI= 1.243-18.358, P= 0.023) has five times increased risk of getting Serratia marcescens compared to TPN. The combination of TPN and Enteral has 69% reduced risk of getting Serratia marcescens compared to TPN alone (OR= 0.311, 95% CI= 0.102-0.951, P= 0.041). However, the combination of TPN and BM has a ten times higher risk of getting Serratia marcescens than TPN alone (OR= 9.905, 95% CI= 2.167-45.275, P= 0.003). Patients who underwent surgery have a four times higher risk of getting Serratia marcescens than those who did not (OR= 3.719, 95% CI= 1.546-8.946, P= 0.003).

Bacteremia was the commonest infection 38.7% (n=36) followed by conjunctivitis 29.0% (n=27). 15 (16.1%) cases had colonization, and 4 (4.3%) cases had wound infection. Meningitis, pneumonia, and urinary tract infection were 1 (1.1%) each. 87% (n=81) of cases were acquired in our hospital, while 13% (n=12) were acquired in other hospitals. 13 (14%) cases had colonization of S. marcescens before infection as shown in (Table 3). All tested  S. marcescens  isolates were resistant to ampicillin and amoxicillin/clavulanate, and all were susceptible to ciprofloxacin, co-trimoxazole and meropenem of the tested isolates: 1.2% were resistant to cefepime, 3.5 % were resistant to gentamicin, 2.4 % resistant to tazocin and 10 % resistant to tigecycline. One S. marcescens isolated from urine tested resistant to nitrofurantoin (Figure 2).

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Discussion

Most of the epidemiology of S. marcescens among neonates are described in the literature is from outbreak settings [6, 7, 8, 9, 10, 11]. Our study highlighted the epidemiology for a ten-year period. The annual incidence and incidence proportion were fluctuating over the years due to occurrence of outbreaks throughout the study period that were ultimately controlled. In a recently reported outbreak, no source was identified [6].

The mortality rate in this study was high as reported by M. Luisa and colleagues that mortality due to S. marcescens infections can vary markedly and range from 0 to 45% [10].

In newborns, the main risk factors for the acquisition of Serratia infection are: immaturity of the immune system and low birth weight (<1500 g) in preterm newborns, length of stay, and the use of antibiotics. (10) In our study the significant risk factors were female gender, C-section, all types of feeding including newborn who are NPO and neonates who had surgery. All these might indicate more handling and care is given to those neonates with element of breaches or non-compliance to infection prevention and control practices during care delivery some of which were highlighted previously. (6) S. marcescens colonizes the preterm infant gut within the first days after birth, following a colonization pattern very similar to that observed in other members of the Family Enterobacteriaceae. Moles et al. found 69% of the infants were colonized by S. marcescens at least in a sampling time during the studied period. The colonization rate increased to ~ 75% when only infants born at < 30 gestational weeks and < 1500 g were considered [11]. The most frequent site of infection in our cohort, as reported in other literature, was bloodstream infection however, conjunctivitis was the second most common.

A few limitations were observed in this report including the study was retrospective in nature and was conducted in one center only which might affect the generalizability of the results. The data for rate of colonization might underestimate as our hospital does not a stable active screening for S. marcescens protocol in the NICU. In addition, we could not do sub analysis for bacteremia as we did not study non-S. Marcescens bacteremia among the controls. The strength of this work is that S. marcescens was studied for 10-year periods and the only one of its kind in the country.

Conclusion

S. marcescens is an important nosocomial pathogen, especially in NICUs, that has a propensity to cause difficult- to-control outbreaks. Healthcare workers’ awareness of this organism and enhancement of infection prevention and control measures is a vital requirement to prevent HAIs among susceptible neonates.