Next Article in Journal
Autism Children and English Vocabulary Learning: A Qualitative Inquiry of the Challenges They Face in Their English Vocabulary Learning Journey
Previous Article in Journal
Gender Differences in Caring for Children with Genetic or Rare Diseases: A Mixed-Methods Study
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Antibiogram of Urinary Tract Infections and Sepsis among Infants in Neonatal Intensive Care Unit

1
Department of Medical Laboratory Science, College of Applied Medical Sciences, University of Ha’il, Hail 55476, Saudi Arabia
2
Department of Medical Microbiology, Qunfudah Faculty of Medicine, Umm Al-Qura University, Al-Qunfudah 21961, Saudi Arabia
3
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
4
Special Infectious Agents Unit, King Fahad Medical Research Center, Jeddah 22252, Saudi Arabia
5
Molecular Diagnostics and Personalized Therapeutics Unit, University of Ha’il, Hail 55476, Saudi Arabia
6
Department of Biology, Turabah University College, Taif University, Turabah 21995, Saudi Arabia
7
Department of Microbiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt
*
Author to whom correspondence should be addressed.
Children 2022, 9(5), 629; https://doi.org/10.3390/children9050629
Submission received: 27 March 2022 / Revised: 17 April 2022 / Accepted: 22 April 2022 / Published: 28 April 2022
(This article belongs to the Section Pediatric Infectious Diseases)

Abstract

:
Neonatal infections including sepsis and urinary tract infections are considered among the leading causes of mortality in neonatal intensive care units (NICU). Thus, use of empiric antibiotics is very important in infected neonates and the success of this practice is mainly reliant on the availability of an up-to-date antibiogram for currently used antibiotic drugs. In this study, we aim to determine the bacteriological profile and antibiotic susceptibility pattern of bacteria isolated from blood or/and urine cultures belonging to patients at the NICU. A total of 54 urine samples were collected in the period between January 2015 and December 2019. Data of infants with positive urine and blood bacterial isolates were gathered retrospectively. The most commonly isolated bacteria from urine observed were K. pneumoniae (44%) and E. coli (39%), while Acinetobacter baumannii (33%) and K. pneumoniae (22%) predominated in neonatal blood samples. The majority of uropathogens and blood isolates exhibited low resistance to imipenem and tigecycline, respectively. These antibiotics would be recommended for future use as empirical treatment in neonates with urinary tract infections and/or sepsis. This investigation highlights the importance of surveillance studies to manage and ensure the effectiveness of treatment plan for critically ill infants.

1. Introduction

Neonates or newborns can be defined as babies from the time of delivery up to four weeks old [1]. Neonates possess an incompetent innate or/and adaptive immunity, which make them more susceptible and less able to compete with infections caused by numerous pathogenic microorganisms [2]. Bacterial infections in newborns can range from mild to severe and life-threating infections, including urinary tract (UTIs) and blood stream infections (BSIs) [3]. Based on the age of neonates when contracting the infection, both BSIs and UTIs can be categorised into two groups: early (during the first 7 days of life) and late (after 7 days from delivery) onset [4]. This is because the immune system of neonates is rapidly developing as they are growing, thus each stage of age may possess different level of potency to fight infections [4]. This fact might explain the reasons behind observed variation of causative bacteria according to baby’s age group [2].
UTIs are very common among neonates, which can be defined as pyuria in urinalysis and a urine culture with 10,000–50,000 colony forming unit (CFU)/mL [5]. Although multiple previous studies indicated the difficulty of conducting urine test for newborns, such a test can be very informative and an alarming sign for serious bacterial infection, especially sepsis [5,6]. Escherichia coli, group B Streptococcus (GBS) and Staphylococcus aureus are well-associated with early and late onset bacterial infections among neonates [7]. Nevertheless, bacterial infections in neonates with vesicoureteral reflux (VUR) are found to be predominately caused by Enterobacter aerogenes, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris and Pseudomonas aeruginosa [5].
The presence of bacteria in the blood without multiplication and production of its toxins is called bacteraemia [8]. However, sepsis can be generally identified by the presence of a proliferating microorganism (e.g., bacteria, virus, parasite, or fungi) or/and their produced toxin/s in the patients’ blood stream leading to haemodynamic changes and clinical manifestations of sepsis [9], which will be the focus of this paper. Sepsis is a worldwide cause of morbidity and mortality in the neonatal intensive care units (NICU) [10]. Moreover, the most common cause of the early onset sepsis in neonates are GBS, Streptococcus agalactiae and E. coli, while the late onset sepsis is caused by GBS, E. coli, Klebsiella species Pseudomonas species, Acinetobacter species and S. aureus [11].
Absence of effective drugs because antimicrobial resistance (AMR) is an unfortunate fact behind the high level of severity of bacterial infections among immunosuppressed individuals, including neonates [12]. It was reported that Gram-negative bacteria (e.g., E. coli, Enterobacter species, Klebsiella species and Pseudomonas species) are well linked with neonates’ infections presented with high level of resistance towards ampicillin, amikacin and gentamycin [13]. Another study revealed a high level of resistance of Gram-negative bacteria against cefotaxime, ceftazidime, amikacin and ciprofloxacin leading to almost four times increasing rate of mortality among infected neonates [14].
In the early onset sepsis, babies could contract the infection before or during the delivery through ascending infection caused by microbial colonization of the maternal perineum or by the direct contact with the causative microorganism during the delivery [15]. Mothers’ vaginal bacterial microbiota were found to be the most common pathogens associated with the early onset bacterial infections among newborns, including sepsis [15]. However, in the late onset sepsis, the source of the infection could be nosocomial [16]. Early and late sepsis in neonates could be caused by multiple Gram-positive and negative bacteria, including coagulase-negative staphylococci (CoNS), E. coli, Enterococci, Haemophilus influenza, Listeria monocytogenes, Pseudomonas aeruginosa, S. aureus and Streptococcus pyogenes [16,17]. Generally, septic pathogens or bacteria is commonly associated with certain infections, including meningitis, pneumonia, arthritis, osteomyelitis, phlebitis, gastroenteritis and UTIs [18]. Thus, it is a very rational practice that clinicians screen for sepsis in patients with these illnesses and vice versa, including UTIs and BSIs.
As the immune system of neonates is not very competent, bacterial infections in this group of patients would require very special care and a treatment plan to avoid any serious complications [2]. Additionally, the increase level of resistance against antibiotic drugs used to treat bacterial infections associated with sepsis and UTI in neonates is very alarming worldwide [19]. Furthermore, use of empirical antibiotics is very important in infected neonates, especially in septic patients, and the success of this kind of practice would mainly relay on the availability of a recent surveillance (antibiogram) for antibiotic resistance nationally and internationally.
The primary goal of antimicrobial stewardship (AMS) is to improve the effective use of antibiotics in different sectors (human, animals, agriculture and aquaculture) worldwide [20]. AMS in human health, especially in hospitals, can be applied by different means, including the availability of antibiogram that is easily accessible by all local physicians [20]. This is because antibiogram would provide doctors with a rational guideline when prescribing empirical antibiotics to treat bacterial infections, particularly life-threating infections such as sepsis [21]. Previous local antibiogram studies have contributed to the development or alteration of first line treatments in numerous scenarios [21]. For instance, the serious challenge of emerging carbapenem-resistant P. aeruginosa in a USA hospital was found to be associated with co-resistance to first-line treatments (beta-lactams) and delayed application of effective empiric antibiotics, thus urgent modification of used antibiotics was carried out [22]. Nevertheless, this observation was only obtained after conducting a local antibiogram study for this bacterium, and this should highlight the importance of antibiogram investigation. Consequently, it is crucial to incorporate an antibiogram into clinical decision to achieve the main goal of providing effective empiric antibiotic therapy. The aim of this project, therefore, is to assess the prevalence of UTIs and its correlations with BSIs among neonates of Hail region in the Kingdom of Saudi Arabia as well as providing recent surveillance data of antibiotics resistance in causative bacteria of these infections.

2. Materials and Methods

2.1. Study Design

A retrospective study was conducted in neonatal intensive care unit (NICU) at Hail Maternity Hospital over a period of five years (January 2015 to December 2019). Medical data of neonates admitted to the NICU (up to 30 days old) with a positive urine culture were obtained from the clinical microbiology laboratory database. Data of neonates with positive blood culture were collected only for those with UTIs to study any potential correlation between UTIs and BSI.

2.2. Study Population

Urine and blood cultures are requested simultaneously by the local clinical doctors for neonates presented with signs and symptoms of septicaemia, including fever (>38 °C), hypothermia (<36 °C), metabolic acidosis, or tachypnoea [23] in the absence of any antibiotic therapy. Urine was collected using short-term urinary catheters (in-and-out catheterisation). Positive urine cultures were identified when the colony forming units (CFU) of a single detected bacterial species were ≥105 CFU/mL [24]. Cultures with polymicrobial growth (>one species) or low number of colonies (<105 CFU/mL) were excluded from this investigation. Blood samples were collected aseptically into an appropriate BACTEC bottle (BD BACTEC™) and incubated at 37 °C using the incubator of the blood culture system (BACTEC-9050, Beckton-Dickenson, Franklin Lakes, NJ, USA) [25].

2.3. Bacterial Identification and Antibiotic Sensitivity Testing

Bacterial identification and antibiotic sensitivity testing were conducted using the VITEK system (bioMerieux, Hampshire, UK) [26]. Obtained data were analysed and interpreted according to the guidelines of the Clinical Laboratory Standards Institute (CLSI) as explained previously [24]. Susceptibility of recovered Gram-negative UTI-related bacteria was evaluated against a panel of antibiotics, including amikacin, ampicillin, cefepime, ceftazidime, cefoxitin, ciprofloxacin, gentamicin, imipenem, meropenem, nitrofurantoin, piperacillin, tigecycline and trimethoprim/sulfamethoxazole. For Gram-positive UTI-associated bacteria, assessment was conducted against ampicillin, cephalothin, clindamycin, levofloxacin, linezolid, moxifloxacin, nitrofurantoin, penicillin, tigecycline, trimethoprim/sulfamethoxazole and vancomycin. The sensitivity testing of ceftazidime against Gram-negative rods was especially conducted to determine extended-spectrum β-lactamase (ESBL) producing strains [27].

2.4. Statistical Analysis

Patients ‘gender, urine and blood culture reports and antibiotic resistance profiles were electronically retrieved from the hospitals’ medical records, and the data were presented as the numbers of cases for each isolated bacterium. Statistical analysis was performed using SPSS software version 16.0 (IBM Corporation, Armonk, NY, USA).

3. Results

3.1. Prevalence of Uropathogens and Septic Bacteria in NICU

A total of 54 (12.6%) of all positive urine cultures during the study period (January 2015 to December 2019) belong to NICU. Males’ neonates account for 66.7% of their urine culture, while the remained portion (33.3%) belong to female neonates. Males were predominant in all five years except in 2015, females were higher than males (9 and 7, respectively). About 9 out of 54 (16.6%) neonates with positive urine culture were identified with bacteraemia. Prevalence of urine associated bacteria among NICU was determined as follows: K. pneumoniae (44%), E. coli (39%), Enterococcus faecalis (7.5%), Pseudomonas aeruginosa (5.6%) and Streptococcus agalactiae (3.8%). In addition, the dissemination of bacteria among septic NICU was calculated as follows: Acinetobacter baumannii (33.3%), K. pneumoniae (22.2%), E. coli (11.1%), P. aeruginosa (11.1%), Staphylococcus aureus (11.1%) and Streptococcus pneumoniae (11.1%).

3.2. Simultaneous Infection/Colonisation of Identified Bacterial Isolates in Blood and Urine of NICU Patients with Positive Blood Cultures

To determine any potential correlation between bacteria identified simultaneously from blood and urine of NICU, data of all neonates with sepsis and positive urine cultures were determined (Table 1). The majority (77%) of identified bacteria in the blood of NICU patients were Gram-negative bacteria (Table 1). Likewise, in urine specimens, about 88% of identified uropathogens in patients with sepsis are Gram-negative bacteria. Nevertheless, about 66% of all Gram-negative uropathogens in neonates with bacteraemia belong to K. pneumoniae (Table 1). Two cases out of 9 septic neonates were identified with identical bacterial species in both specimens (blood and urine) (Table 1).

3.3. Sensitivity Profiles of Identified Gram-Negative Bacteria from Blood and Urine of NICU Patients

Susceptibility profiles were determined for isolates recovered from urine and/or blood specimens using 12 commonly used antibiotics in the local hospital. Urine isolates of non-ESBL producing strains of E. coli and K. pneumoniae showed high percentage of resistance to piperacillin and trimethoprim/sulfamethoxazole, whereas wide sensitivity (zero resistance) of these isolates towards cefoxitin was also monitored (Table 2). In addition, a high portion of K. pneumoniae ESBL-producing strains isolated from urine and/or blood cultures of neonates exhibited resistance to ampicillin, cefepime and gentamicin, while absent resistance by the same strains was detected when using imipenem, meropenem and tigecycline (Table 2). About 85% of K. pneumoniae ESBL-producing showed resistance to cefepime, while the same drug was completely active with zero resistance towards non-ESBL producing strains of this bacterium (Table 2). Furthermore, the majority of tested antibiotics showed limited activity against ESBL and non-ESBL Pseudomonas aeruginosa recovered from urine and/or blood cultures of neonates except piperacillin as its broad activity towards all strains of P. aeruginosa was observed (Table 2). Acinetobacter baumannii that was isolated from blood of NICU were totally resistant to all tested antibiotics, except tigecycline only (Table 2).

3.4. Sensitivity Profiles of Identified Gram-Positive Bacteria from Blood and Urine of NICU Patients

A quarter and half of Enterococcus faecalis and Streptococcus agalactiae isolated from urine were resistant to clindamycin, nitrofurantoin and trimethoprim/sulfamethoxazole, respectively (Table 3). Blood isolates of methicillin-sensitive Staphylococcus aureus (MSSSA) were susceptible to almost all tested antibiotics, excluding trimethoprim/sulfamethoxazole. On the other hand, blood associated Streptococcus pneumoniae exhibited a high level of resistance to all used antibiotics apart from vancomycin and tigecycline (Table 3).

4. Discussion

There are multiple factors that have been linked with the emergence and spread of multidrug resistant bacteria (MDR) worldwide, including unguided use/prescribing of antibiotic drugs [28]. Infection with drug resistant bacteria carries a high rate of mortality, especially among immune compromised individuals, such as newborns [28]. Prevalence of UTI amongst neonates varies between studies which ranged from 7% to 15% based on the sample size and location of the study [29]. Thus, this study was designed to identify the uropathogens and potential association with septic bacteria among NICU in Hail region, Saudi Arabia, between 2015 and 2019.
The current investigation includes patients who were admitted to the NICU that made about 12.6% (54) of all positive urine cultures during the study period. The majority of neonatal positive urine cultures belong to male patients in all five years, except 2015. Among these neonates with UTIs, sepsis was identified in 9 of 54 (16.6%) newborns. This finding would lead to the suggestion that male newborns are more prone to contract UTIs than females. This observation was backed up by a prior similar study reporting that the prevalence of UTIs among boys was higher than girls with the following calculated ratio: (4.5:1) [30]. Generally, UTIs tend to be more frequent in females than in male individuals across all age groups based on the actual differences in the length of their urethra and anatomical differences in males [31], and this would be the possible reason behind the higher rate of UTIs in females compared to males. However, this was not the case when referring to uncircumcised males as multiple studies have revealed their high vulnerability to contracting UTIs compared with their circumcised counterparts [32]. Male are predominant (90%) in neonates with UTI aged less than 30 days in a ten years study [26]. Uncircumcised infant boys aged less than 60 days have had higher rate of UTIs (21%), compared to their circumcised counterparts (2%) and girls (5%) [5]. This fact might explain the high percentage (66%) of UTIs in male neonates as they may not undergo any circumcision at this stage.
It was claimed that neonates with positive urine cultures would possess a higher probability to develop sepsis [33]. About third of neonates who were diagnosed with UTI presented with positive blood cultures and sepsis [33]. Currently, about 16% of neonates have had urosepsis, and this would agree with a report from China where 11% of neonates with UTI have had septicaemia [34]. Neonates admitted to the NICU are usually considered as critically ill patients, which means the use of central lines could be a necessity, although use of central lines is strongly linked with an increased risk of BSIs [35]. Therefore, high prevalence of septicaemia are reported among NICU where active antibiotic should be implemented immediately [36].
Generally, Gram-negative bacteria are more prevalent in urine and blood specimens of patients in the NICU compared to Gram-positive bacteria. Klebsiella pneumoniae and E. coli were the top identified bacteria from urine cultures of neonates, while Acinetobacter baumannii was observed more often in septic neonates. In line with previous reports, Klebsiella species and E. coli were found to be the bacteria most commonly associated with infections of newborns [37,38,39]. In addition, a big portion of the UTI infections in neonates are due to K. pneumoniae and E. coli, which were more linked with males than females [40]. Moreover, the majority (77%) of detected bacteria from blood samples of patients at the NICU were Gram-negative bacteria and roughly 88 percent of identified uropathogens in septic patients. Nevertheless, K. pneumoniae is responsible for around two thirds of Gram-negative uropathogens in neonates with sepsis, and only 22% of BSIs were caused by Gram-positive bacteria, including Staphylococcus aureus and Streptococcus pneumoniae.
In paediatric UTI, young age is a well-known risk factor for sepsis [41]. Previous study demonstrated that E. coli and K. pneumoniae were the two most common pathogens (81.2%) in UTIs [42]. According to other studies, E. coli is the most common cause of UTIs in neonates [43]. However, certain studies have shown that the total burden of disease caused by E. coli was lower in young age group (approximately 50% of all positive cultures) than in older age groups, in which E. coli was responsible for up to 80% of UTIs. Male newborns with VUR were more likely than female infants to have UTIs caused by K. pneumoniae, K. oxytoca, Proteus mirabilis, Proteus vulgaris, Enterobacter aerogenes and Pseudomonas aeruginosa [26,44]. Although occurrences of Enterococcus faecalis, Staphylococcus aureus, Group B Streptococcus and Streptococcus pneumonia infections in newborns are uncommon, cases of Enterococcus faecalis, Staphylococcus aureus, Group B Streptococcus and Streptococcus pneumonia have been reported [45].
Sensitivity profiles of non-extended spectrum β-lactamase (non-ESBL) K. pneumoniae strains that were detected from urine samples of neonates showed high percentages of resistance to piperacillin and trimethoprim/sulfamethoxazole, whereas the high sensitivity of these isolates to cefoxitin was monitored. Meanwhile, K. pneumoniae ESBL strains were resistant to ampicillin, cefepime and gentamicin, except imipenem, meropenem and/or tigecycline. In line with Pokhrel et al. [46], the majority of ESBL producing K. pneumoniae (85%) were resistant to cefepime. Additionally, a high resistance rate was reported for K. pneumoniae against trimethoprim/sulfamethoxazole followed by piperacillin, cefotaxime, cefepime and aztreonam, while colistin drug showed a high level of activity towards the same isolates [47].
Culturing of blood samples revealed that the most common bacterial isolate was K. pneumoniae and that the majority of isolates were highly resistant to gentamicin and ampicillin (Table 1). Escherichia coli isolates have been reported with high sensitivity to ampicillin and cefepime in the Hail region [24]. A combination therapy made of gentamicin and ampicillin would be recommended as empirical treatment for neonates with UTI or/and sepsis in the local hospital. Thus, this study highlights the importance of antibiogram to ensure the effectiveness of therapeutic drugs.
Nonetheless, previous neonatal research had identified coagulase negative staphylococcus aureus (CoNs) as predominant bacterial species associated with blood specimens [48]. Variation among location of studies, size of recruited patients and level of adherence to hand hygiene techniques would explain the difference in the prevalence of bacteria associated with neonatal infections.
Concerning the sensitivity profile, A. baumannii was resistant to all tested antibiotics except for tigecycline. The resistance profile of A. baumannii was claimed by Shaw et al. [49] although another study indicated the high sensitivity of tested A. baumannii strains to ciprofloxacin and colistin as well as tigecycline [46]. Tigecycline was successfully used previously to treat extensively drug-resistant Klebsiella pneumoniae in septic neonates [50]. Additionally, although tigecycline was effectively applied to eradicate extensively drug-resistant Acinetobacter baumannii in infected neonates, usage of tigecycline in this group of patients in relation to its safety might be questionable [51]. However, using tigecycline in neonates with life-threating infections such as sepsis, especially where an alternative, safer and active therapeutic agent is missing, was justified [51]. Thus, the current antibiogram would propose the local potential use of tigecycline as an empirical drug in neonates with sepsis caused by Acinetobacter baumannii. Nevertheless, this data may not be representative of another region within the kingdom or worldwide. This is due to the observed differences among the sensitivity profiles of A. baumannii strains from one location to another, which may attributed to the variation of therapeutic drugs used locally for treating this bacterium. Multiple strains of Pseudomonas aeruginosa were tested against 12 antibiotics, all of which were sensitive to imipenem and meropenem. A previous study presented similar data to the current findings in which eight isolates were tested against the antibiotics used in this study, showing resistance to ciprofloxacin and tigecycline [52]. Multiple former studies have reported the high sensitivity of Enterococcus faecalis towards vancomycin [53]. Enterococcus faecalis and Streptococcus agalactiae were also assessed in the present study where they were resistant to clindamycin, nitrofurantoin and trimethoprim/sulfamethoxazole. This observation is in agreement with Karthikeyan et al., who reported that all tested isolates of Enterococcus faecalis and Streptococcus agalactiae were sensitive to vancomycin (100%) [54].
The results of the current antibiogram are an essential tool for local hospitals and policy makers in Saudi Arabia to track bacterial resistance and change their choice of empirical drugs accordingly to ensure their activity and thus control the spread of AMR. In addition, sensitivity profiles among bacterial isolates nationally and worldwide over a short period of time were varied [20], and this would indicate the importance of conducting frequently a local antimicrobial surveillance study. Having local and up-to-date antibiogram data does not necessarily means better prescription of antibiotics and limited spread of AMR, unless antibiogram data are well distributed and utilised by the local health care workers (HCWs). This can be achieved by different means, including a series of targeted meetings for local clinical microbiologists and physicians to raise awareness about the importance of establishing and using local antibiogram data. This is because using local antibiogram effectively could lead to a significant reduction in inappropriate prescription of antibiotics, level of local AMR, rate of local hospitalisation and rate of probability for local patients to develop serious complications from infections and death.
Although this study has assessed the prevalence of UTIs and their correlation with BSIs among infants in NICU, it has several limitations. The number of recruited patients may not be representative of all neonates with different types of infections, since larger populations with wider bacterial infections could lead to better outcomes. In addition, the limited number of Gram-positive bacteria and the absence of Listeria monocytogenes could also be considered as potential limitations.

5. Conclusions

Gram-negative bacteria were the major cause of UTIs and sepsis among ICU babies. The most common causes of UTIs were K. pneumoniae and E. coli while sepsis was caused by Acinetobacter baumannii and K. pneumoniae. Urine and blood isolates showed K. pneumoniae and E. coli with ESBL and non-ESBL activity. The non-ESBLs were highly resistant to piperacillin and trimethoprim/sulfamethoxazole; on the other hand, the ESBLs were resistant to ampicillin, cefepime and gentamicin. Piperacillin and tigecycline were the only active drug against P. aeruginosa and A. baumannii, respectively. The majority of uropathogens and blood isolates exhibited low resistance to imipenem and tigecycline, respectively, which can be proposed for potential usage as empirical treatment in neonates with sepsis and UTIs. These data highlight the importance of surveillance studies in managing critically ill infants.

Author Contributions

Conceptualization, A.S.B. and A.A. (Abdu Aldarhami); formal analysis, A.A. (Abdu Aldarhami), H.G. and G.A.; funding acquisition, A.S.B.; investigation, A.S.B., A.A. (Abdu Aldarhami), H.G., H.B., H.Q., G.A. and B.A.; methodology, A.S.B., A.A. (Abdu Aldarhami) and H.Q.; data collection, A.S.B. and A.A. (Abdulaziz Alrashidi); original draft, A.A. (Abdu Aldarhami), H.Q. and E.H.E.; review and editing, A.S.B., A.A. (Abdu Aldarhami), H.G., H.B., H.Q., G.A., B.A., A.A. (Abdulaziz Alrashidi) and E.H.E. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Scientific Research Deanship at University of Ha’il-Saudi Arabia via a project number (RG-21071).

Institutional Review Board Statement

This study was approved on 23 March 2020 by the Ethics Committee at the University of Ha’il, Saudi Arabia (reference number H-2020-048). Patients’ privacy and confidentiality of data were maintained in accordance with the Declaration of Helsinki.

Informed Consent Statement

Patient consent was waived because this was retrospective study with no interaction with patients.

Data Availability Statement

All data are available within the manuscript.

Acknowledgments

All authors thank the Scientific Research Deanship at University of Ha’il for their grant through a project number (RG-21071).

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Black, R.E.; Cousens, S.; Johnson, H.L.; Lawn, J.E.; Rudan, I.; Bassani, D.G.; Jha, P.; Campbell, H.; Walker, C.F.; Cibulskis, R.; et al. Global, regional, and national causes of child mortality in 2008: A systematic analysis. Lancet 2010, 375, 1969–1987. [Google Scholar] [CrossRef]
  2. Basha, S.; Surendran, N.; Pichichero, M. Immune responses in neonates. Expert Rev. Clin. Immunol. 2014, 10, 1171–1184. [Google Scholar] [CrossRef] [PubMed]
  3. Sass, L.; Karlowicz, M.G. Healthcare-Associated Infections in the Neonate. Princ. Pract. Pediatr. Infect. Dis. 2018, 3, 560–566. [Google Scholar] [CrossRef]
  4. Cortese, F.; Scicchitano, P.; Gesualdo, M.; Filaninno, A.; De Giorgi, E.; Schettini, F.; Laforgia, N.; Ciccone, M.M. Early and Late Infections in Newborns: Where Do We Stand? A Review. Pediatr. Neonatol. 2016, 57, 265–273. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  5. Arshad, M.; Seed, P.C. Urinary tract infections in the infant. Clin. Perinatol. 2015, 42, 17–28. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  6. Walawender, L.; Hains, D.S.; Schwaderer, A.L. Diagnosis and imaging of neonatal UTIs. Pediatr. Neonatol. 2020, 61, 195–200. [Google Scholar] [CrossRef] [PubMed]
  7. Simonsen, K.A.; Anderson-Berry, A.L.; Delair, S.F.; Davies, H.D. Early-onset neonatal sepsis. Clin. Microbiol. Rev. 2014, 27, 21–47. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  8. Hamer, D.H.; Darmstadt, G.L.; Carlin, J.B.; Zaidi, A.K.M.; Yeboah-Antwi, K.; Saha, S.K.; Ray, P.; Narang, A.; Mazzi, E.; Kumar, P.; et al. Etiology of Bacteremia in Young Infants in Six Countries. Pediatr. Infect. Dis. J. 2015, 34, e1–e8. [Google Scholar] [CrossRef] [Green Version]
  9. Kaufman, D.; Fairchild, K.D. Clinical microbiology of bacterial and fungal sepsis in very-low-birth-weight infants. Clin. Microbiol. Rev. 2004, 17, 638–680. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  10. Fleischmann, C.; Reichert, F.; Cassini, A.; Horner, R.; Harder, T.; Markwart, R.; Tröndle, M.; Savova, Y.; Kissoon, N.; Schlattmann, P.; et al. Global incidence and mortality of neonatal sepsis: A systematic review and meta-analysis. Arch. Dis. Child. 2021, 106, 745–752. [Google Scholar] [CrossRef] [PubMed]
  11. Almohammady, M.N.; Eltahlawy, E.M.; Reda, N.M. Pattern of bacterial profile and antibiotic susceptibility among neonatal sepsis cases at Cairo University Children Hospital. J. Taibah Univ. Med. Sci. 2020, 15, 39–47. [Google Scholar] [CrossRef] [PubMed]
  12. Ayukekbong, J.A.; Ntemgwa, M.; Atabe, A.N. The threat of antimicrobial resistance in developing countries: Causes and control strategies. Antimicrob. Resist. Infect. Control 2017, 6, 47. [Google Scholar] [CrossRef] [PubMed]
  13. Tamma, P.D.; Cosgrove, S.E.; Maragakis, L.L. Combination therapy for treatment of infections with gram-negative bacteria. Clin. Microbiol. Rev. 2012, 25, 450–470. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  14. Shehab El-Din, E.M.R.; El-Sokkary, M.M.A.; Bassiouny, M.R.; Hassan, R. Epidemiology of Neonatal Sepsis and Implicated Pathogens: A Study from Egypt. BioMed Res. Int. 2015, 2015, 509484. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  15. Chan, G.J.; Lee, A.C.C.; Baqui, A.H.; Tan, J.; Black, R.E. Risk of early-onset neonatal infection with maternal infection or colonization: A global systematic review and meta-analysis. PLoS Med. 2013, 10, e1001502. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. Bulkowstein, S.; Ben-Shimol, S.; Givon-Lavi, N.; Melamed, R.; Shany, E.; Greenberg, D. Comparison of early onset sepsis and community-acquired late onset sepsis in infants less than 3 months of age. BMC Pediatr. 2016, 16, 82. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  17. Berardi, A.; Sforza, F.; Baroni, L.; Spada, C.; Ambretti, S.; Biasucci, G.; Bolognesi, S.; Capretti, M.; Carretto, E.; Ciccia, M.; et al. Epidemiology and complications of late-onset sepsis: An Italian area-based study. PLoS ONE 2019, 14, e0225407. [Google Scholar] [CrossRef] [Green Version]
  18. Ghorashi, Z.; Nezami, N.; Hoseinpour-Feizi, H.; Ghorashi, S.; Tabrizi, J.S. Arthritis, osteomyelitis, septicemia and meningitis caused by Klebsiella in a low-birth-weight newborn: A case report. J. Med. Case Rep. 2011, 5, 241. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  19. Vazouras, K.; Velali, K.; Tassiou, I.; Anastasiou-Katsiardani, A.; Athanasopoulou, K.; Barbouni, A.; Jackson, C.; Folgori, L.; Zaoutis, T.; Basmaci, R.; et al. Antibiotic treatment and antimicrobial resistance in children with urinary tract infections. J. Glob. Antimicrob. Resist. 2020, 20, 4–10. [Google Scholar] [CrossRef] [PubMed]
  20. Doron, S.; Davidson, L.E. Antimicrobial stewardship. Mayo Clin. Proc. 2011, 86, 1113–1123. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  21. Truong, W.R.; Hidayat, L.; Bolaris, M.A.; Nguyen, L.; Yamaki, J. The antibiogram: Key considerations for its development and utilization. JAC Antimicrob. Resist. 2021, 3, dlab060. [Google Scholar] [CrossRef] [PubMed]
  22. Monteiro, A.C.M.; Fortaleza, C.M.C.B.; Ferreira, A.M.; Cavalcante, R.d.S.; Mondelli, A.L.; Bagagli, E.; da Cunha, M.d.L.R.d.S. Comparison of methods for the identification of microorganisms isolated from blood cultures. Ann. Clin. Microbiol. Antimicrob. 2016, 15, 45. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  23. Khassawneh, M.; Khader, Y.; Abuqtaish, N. Clinical features of neonatal sepsis caused by resistant Gram-negative bacteria. Pediatr. Int. 2009, 51, 332–336. [Google Scholar] [CrossRef] [PubMed]
  24. Bazaid, A.S.; Saeed, A.; Alrashidi, A.; Alrashidi, A.; Alshaghdali, K.; Hammam, S.A.; Alreshidi, T.; Alshammary, M.; Alarfaj, A.; Thallab, R.; et al. Antimicrobial Surveillance for Bacterial Uropathogens in Ha’il, Saudi Arabia: A Five-Year Multicenter Retrospective Study. Infect. Drug Resist. 2021, 14, 1455–1465. [Google Scholar] [CrossRef] [PubMed]
  25. Lugira, Y.S.; Kimaro, F.D.; Mkhoi, M.L.; Mafwenga, S.G.; Joho, A.A.; Yahaya, J.J. Prevalence, aetiology, antimicrobial susceptibility testing, and predictors of urinary tract infection among neonates with clinical sepsis: A cross-sectional study. Egypt. Pediatr. Assoc. Gaz. 2022, 70, 2. [Google Scholar] [CrossRef]
  26. Bonadio, W.; Maida, G. Urinary tract infection in outpatient febrile infants younger than 30 days of age: A 10-year evaluation. Pediatr. Infect. Dis. J. 2014, 33, 342–344. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  27. Alqasim, A.; Abu Jaffal, A.; Alyousef, A.A. Prevalence of Multidrug Resistance and Extended-Spectrum β-Lactamase Carriage of Clinical Uropathogenic Escherichia coli Isolates in Riyadh, Saudi Arabia. Int. J. Microbiol. 2018, 2018, 3026851. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  28. Prestinaci, F.; Pezzotti, P.; Pantosti, A. Antimicrobial resistance: A global multifaceted phenomenon. Pathog. Glob. Health 2015, 109, 309–318. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  29. Hoberman, A.; Chao, H.P.; Keller, D.M.; Hickey, R.; Davis, H.W.; Ellis, D. Prevalence of urinary tract infection in febrile infants. J. Pediatr. 1993, 123, 17–23. [Google Scholar] [CrossRef]
  30. Yoon, S.H.; Shin, H.; Lee, K.H.; Kim, M.K.; Kim, D.S.; Ahn, J.G.; Shin, J.I. Predictive factors for bacteremia in febrile infants with urinary tract infection. Sci. Rep. 2020, 10, 4469. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  31. Megged, O. Bacteremic vs nonbacteremic urinary tract infection in children. Am. J. Emerg. Med. 2017, 35, 36–38. [Google Scholar] [CrossRef] [PubMed]
  32. Tobian, A.A.R.; Gray, R.H.; Quinn, T.C. Male circumcision for the prevention of acquisition and transmission of sexually transmitted infections: The case for neonatal circumcision. Arch. Pediatr. Adolesc. Med. 2010, 164, 78–84. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  33. Ginsburg, C.M.; McCracken, G.H., Jr. Urinary tract infections in young infants. Pediatrics 1982, 69, 409–412. [Google Scholar] [CrossRef] [PubMed]
  34. Wang, S.F.; Huang, F.Y.; Chiu, N.C.; Tsai, T.C.; Ho, U.Y.; Kao, H.A.; Hsu, C.H.; Hung, H.Y. Urinary tract infection in infants less than 2 months of age. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi 1994, 35, 294–300. [Google Scholar] [PubMed]
  35. Mohseny, A.B.; van Velze, V.; Steggerda, S.J.; Smits-Wintjens, V.E.H.J.; Bekker, V.; Lopriore, E. Late-onset sepsis due to urinary tract infection in very preterm neonates is not uncommon. Eur. J. Pediatr. 2018, 177, 33–38. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  36. Pitetti, R.D.; Choi, S. Utility of blood cultures in febrile children with UTI. Am. J. Emerg. Med. 2002, 20, 271–274. [Google Scholar] [CrossRef] [PubMed]
  37. Saha, S.K.; Schrag, S.J.; El Arifeen, S.; Mullany, L.C.; Shahidul Islam, M.; Shang, N.; Qazi, S.A.; Zaidi, A.K.M.; Bhutta, Z.A.; Bose, A.; et al. Causes and incidence of community-acquired serious infections among young children in south Asia (ANISA): An observational cohort study. Lancet 2018, 392, 145–159. [Google Scholar] [CrossRef] [Green Version]
  38. Zaidi, A.K.; Thaver, D.; Ali, S.A.; Khan, T.A. Pathogens associated with sepsis in newborns and young infants in developing countries. Pediatr. Infect. Dis. J. 2009, 28, S10–S18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  39. Seale, A.C.; Mwaniki, M.; Newton, C.R.; Berkley, J.A. Maternal and early onset neonatal bacterial sepsis: Burden and strategies for prevention in sub-Saharan Africa. Lancet Infect. Dis. 2009, 9, 428–438. [Google Scholar] [CrossRef] [Green Version]
  40. Leung, A.K.C.; Wong, A.H.C.; Leung, A.A.M.; Hon, K.L. Urinary Tract Infection in Children. Recent Pat. Inflamm. Allergy Drug Discov. 2019, 13, 2–18. [Google Scholar] [CrossRef]
  41. Gomez, B.; Diaz, H.; Carro, A.; Benito, J.; Mintegi, S. Performance of blood biomarkers to rule out invasive bacterial infection in febrile infants under 21 days old. Arch. Dis. Child. 2019, 104, 547–551. [Google Scholar] [CrossRef] [PubMed]
  42. Bahat Ozdogan, E.; Mutlu, M.; Camlar, S.A.; Bayramoglu, G.; Kader, S.; Aslan, Y. Urinary tract infections in neonates with unexplained pathological indirect hyperbilirubinemia: Prevalence and significance. Pediatr. Neonatol. 2018, 59, 305–309. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  43. Didier, C.; Streicher, M.P.; Chognot, D.; Campagni, R.; Schnebelen, A.; Messer, J.; Donato, L.; Langer, B.; Meyer, N.; Astruc, D.; et al. Late-onset neonatal infections: Incidences and pathogens in the era of antenatal antibiotics. Eur. J. Pediatr. 2012, 171, 681–687. [Google Scholar] [CrossRef] [PubMed]
  44. Lo, D.S.; Shieh, H.H.; Ragazzi, S.L.; Koch, V.H.; Martinez, M.B.; Gilio, A.E. Community-acquired urinary tract infection: Age and gender-dependent etiology. Braz. J. Nephrol. 2013, 35, 93–98. [Google Scholar] [CrossRef] [PubMed]
  45. Bitsori, M.; Maraki, S.; Raissaki, M.; Bakantaki, A.; Galanakis, E. Community-acquired enterococcal urinary tract infections. Pediatr. Nephrol. 2005, 20, 1583–1586. [Google Scholar] [CrossRef] [PubMed]
  46. Pokhrel, B.; Koirala, T.; Shah, G.; Joshi, S.; Baral, P. Bacteriological profile and antibiotic susceptibility of neonatal sepsis in neonatal intensive care unit of a tertiary hospital in Nepal. BMC Pediatr. 2018, 18, 208. [Google Scholar] [CrossRef] [PubMed]
  47. Ibrahim, M.E. High antimicrobial resistant rates among Gram-negative pathogens in intensive care units. A retrospective study at a tertiary care hospital in Southwest Saudi Arabia. Saudi Med. J. 2018, 39, 1035–1043. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  48. Marchant, E.A.; Boyce, G.K.; Sadarangani, M.; Lavoie, P.M. Neonatal sepsis due to coagulase-negative staphylococci. Clin. Dev. Immunol. 2013, 2013, 586076. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  49. Shaw, C.K.; Shaw, P.; Thapalial, A. Neonatal sepsis bacterial isolates and antibiotic susceptibility patterns at a NICU in a tertiary care hospital in western Nepal: A retrospective analysis. Kathmandu Univ. Med. J. (KUMJ) 2007, 5, 153–160. [Google Scholar]
  50. İpek, M.Ş.; Gunel, M.; Özbek, E. Tigecycline Use in Neonates: 5-Year Experience of a Tertiary Center. J. Pediatric Infect. Dis. 2018, 14, 103–107. [Google Scholar] [CrossRef]
  51. Zeng, J.; Zhang, L.; Gao, M.; Wu, J.; Wu, H.; Chen, J.; Chen, X.; Tang, W. Tigecycline treatment in an infant with extensively drug-resistant Acinetobacter baumannii bacteremia. Int. J. Infect. Dis. 2017, 61, 23–26. [Google Scholar] [CrossRef] [PubMed]
  52. Chelliah, A.; Thyagarajan, R.; Katragadda, R.; Leela, K.V.; Babu, R.N. Isolation of MRSA, ESBL and AmpC-β -lactamases from Neonatal Sepsis at a Tertiary Care Hospital. J. Clin. Diagn. Res. 2014, 8, DC24–DC27. [Google Scholar] [CrossRef] [PubMed]
  53. Dalal, P.; Gathwala, G.; Gupta, M.; Singh, J. Bacteriological profile and antimicrobial sensitivity pattern in neonatal sepsis: A study from North India. Int. J. Res. Med. Sci. 2017, 5, 1541. [Google Scholar] [CrossRef]
  54. Karthikeyan, G.; Premkumar, K. Neonatal sepsis: Staphylococcus aureus as the predominant pathogen. Indian J. Pediatr. 2001, 68, 715–717. [Google Scholar] [CrossRef] [PubMed]
Table 1. Simultaneous infection/colonisation of identified bacterial isolates in blood and urine of neonatal intensive care unit (NICU) patients with positive blood cultures.
Table 1. Simultaneous infection/colonisation of identified bacterial isolates in blood and urine of neonatal intensive care unit (NICU) patients with positive blood cultures.
Neonates with SepsisIdentified Bacteria
in the Blood
Identified Bacteria
in the Urine
Case 1Acinetobacter baumanniiKlebsiella pneumoniae
Case 2Acinetobacter baumanniiKlebsiella pneumoniae
Case 3Acinetobacter baumanniiStreptococcus agalactiae
Case 4Escherichia coli *Escherichia coli *
Case 5Klebsiella pneumoniaeEscherichia coli
Case 6Klebsiella pneumonia *Klebsiella pneumoniae *
Case 7Pseudomonas aeruginosaKlebsiella pneumoniae
Case 8Staphylococcus aureusKlebsiella pneumoniae
Case 9Streptococcus pneumoniaeKlebsiella pneumoniae
* Indicates patients identified with identical bacterial species from urine and blood specimens.
Table 2. Resistance profiles of Gram-negative bacteria isolated from positive urine and blood cultures towards a set of commonly used antibiotics in neonatal intensive care unit (NICU).
Table 2. Resistance profiles of Gram-negative bacteria isolated from positive urine and blood cultures towards a set of commonly used antibiotics in neonatal intensive care unit (NICU).
-Number of IsolatesAmikacinAmpicillinCefepimeCefoxitinCiprofloxacinGentamicinImipenemNitrofurantoinMeropenemPiperacillinTigecyclineTrimethoprim/Sulfamethoxazole
Urine isolates
Escherichia coli214 (19)03 (14)07 (33)7 (33)4 (19)5 (24)3 (14)9 (43)6 (29)13 (62)
Klebsiella pneumoniae177 (41)1 (6)002 (12)7 (41)02 (12)03 (18)2 (12)3 (18)
Klebsiella pneumoniae ESBL *74 (57)5 (71)6 (86)1 (14)3 (43)5 (71)01 (14)01 (14)01 (14)
Pseudomonas aeruginosa32 (67)2 (67)01 (33)1 (33)2 (67)02 (67)002 (67)3 (100)
Blood isolates
Klebsiella pneumoniae ESBL *21 (50)1 (50)2 (100)1 (50)01 (50)000000
Pseudomonas aeruginosa ESBL *101 (100)1 (100)1 (100)1 (100)1 (100)1 (100)01 (100)001 (100)
Acinetobacter baumannii33 (100)3 (100)3 (100)3 (100)3 (100)3 (100)3 (100)3 (100)3 (100)3 (100)03 (100)
Data are presented as the total number of resistant isolates during the study period. Numbers in brackets are percentages. * Isolates resistant to ceftazidime (third generation cephalosporin) are considered as extended-spectrum β-lactamase producing. Resistance profile of bacterial isolate present in both urine and blood was included among urine isolates only.
Table 3. Resistance profiles of Gram-positive bacteria isolated from neonates with urinary tract infections (UTIs) during a 5-year period (2015–2019) towards a set of commonly used antibiotics.
Table 3. Resistance profiles of Gram-positive bacteria isolated from neonates with urinary tract infections (UTIs) during a 5-year period (2015–2019) towards a set of commonly used antibiotics.
-Number of IsolatesCephalothinClindamycinLevofloxacin LinezolidMoxifloxacinNitrofurantoinPenicillinTigecyclineTrimethoprim/SulfamethoxazoleVancomycin
Urine isolates
Enterococcus faecalis401 (25)0001 (25)00 1 (25)1 (25)
Streptococcus agalactiae201 (50)0001 (50)1 (50)01 (50)0
Blood isolates
Staphylococcus aureus11 (100)000001 (100)01 (100)0
Streptococcus pneumoniae11 (100)01 (100)1 (100)1 (100)1 (100)1 (100)01 (100)0
Data presented as the total number of resistant strains isolated during the study period. Numbers in brackets are percentages.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Bazaid, A.S.; Aldarhami, A.; Gattan, H.; Barnawi, H.; Qanash, H.; Alsaif, G.; Alharbi, B.; Alrashidi, A.; Eldrehmy, E.H. Antibiogram of Urinary Tract Infections and Sepsis among Infants in Neonatal Intensive Care Unit. Children 2022, 9, 629. https://doi.org/10.3390/children9050629

AMA Style

Bazaid AS, Aldarhami A, Gattan H, Barnawi H, Qanash H, Alsaif G, Alharbi B, Alrashidi A, Eldrehmy EH. Antibiogram of Urinary Tract Infections and Sepsis among Infants in Neonatal Intensive Care Unit. Children. 2022; 9(5):629. https://doi.org/10.3390/children9050629

Chicago/Turabian Style

Bazaid, Abdulrahman S., Abdu Aldarhami, Hattan Gattan, Heba Barnawi, Husam Qanash, Ghaida Alsaif, Bandar Alharbi, Abdulaziz Alrashidi, and Essam Hassan Eldrehmy. 2022. "Antibiogram of Urinary Tract Infections and Sepsis among Infants in Neonatal Intensive Care Unit" Children 9, no. 5: 629. https://doi.org/10.3390/children9050629

APA Style

Bazaid, A. S., Aldarhami, A., Gattan, H., Barnawi, H., Qanash, H., Alsaif, G., Alharbi, B., Alrashidi, A., & Eldrehmy, E. H. (2022). Antibiogram of Urinary Tract Infections and Sepsis among Infants in Neonatal Intensive Care Unit. Children, 9(5), 629. https://doi.org/10.3390/children9050629

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop