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Fight to Survive: An Analysis of the Factors Related to the Control and Elimination of Outbreaks of Multidrug Resistant Bacteria in the Neonatal Intensive Care Units
Written By
Santiago Garzón and Fernando Aguinaga
Submitted: 02 August 2023Reviewed: 27 September 2023Published: 07 November 2023
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The purpose of this chapter is to provide the reader with applicable guidance on the management of outbreaks and infections of multi-resistant bacteria in the neonatal intensive care unit. The main focus will be on the different strategies for the prevention and control of outbreaks of multi-resistant bacteria, these being applied to the personnel and infrastructure of the unit. A brief comparative analysis of different neonatal intensive care units around the world and the similarities and differences in the management of outbreaks and infections will be carried out. The importance of sanitary and epidemiological surveillance and monitoring of outbreaks that can potentially occur in the pediatric intensive care unit, will be addressed in a practical way.
*Address all correspondence to: santi_garzon@hotmail.com
1. Introduction
Neonatal Intensive Care Units represent an environment that must remain relatively free of resistant and multi-resistant pathogens, since this is the area where all newborns coming directly from the delivery room after being in the uterine environment [1].
Outbreaks of bacterial growth, and nosocomial infections acquired in the hospital environment, represent a major global public health problem, having a high frequency in infants hospitalized in the neonatal intensive care area, with a frequency range that varies from 8 to 30%. This data is important, and at the same time alarming, since the mortality and morbidity rate of neonates requiring intensive care increases due to their low immunity, and other associated risk factors such as low birth weight, use of central lines, use of parenteral nutrition, invasive procedures, and early exposure to antibiotics [2, 3].
Mainly, the early and prolonged use of antibiotics, added to the long hospital stays of neonates in intensive care, has allowed a heterogeneous group of resistant and multi-resistant bacteria to cause infectious outbreaks in critical hospital areas.
Among the most important bacteria that cause infectious outbreaks in neonatal intensive care areas we have the Enterobacteriaceae family, which are a group of gram-negative, facultative anaerobic bacteria that are saprophytes of the digestive tract, being responsible for between 20% and 40% of late sepsis in neonatal intensive care units [1].
One of the main bacteria in this group is Klebsiella pneumoniae, which represents a serious threat to public health, since it is a resistant multidrug bacterium. Other multi-resistant bacteria that occur to a lesser extent, but are the cause of neonatal morbidity and mortality, are Serratia marcescens, Acinetobacter baumanii, Meticillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococcus [4, 5].
The main objective of this chapter is to describe in a practical and didactical way the clinical, epidemiological and microbiological characteristics; and the main intervention measures, to contain or eradicate outbreaks of multi-resistant bacteria in neonatal intensive care units.
2. Determinant measures in the control and elimination of outbreaks of multidrug-resistant bacteria in neonatal intensive care units
The presence of outbreaks of multidrug-resistant bacteria in neonatal intensive care units, and the colonization of hospitalized neonates by those bacteria, is a worrying issue, not only because of the possibility of intestinal or skin colonization, and subsequent hematogenous dissemination causing nosocomial infections; but also, by the chain of transmission of bacteria between health personnel and the environment, creating reservoirs of those bacteria, and multi-resistant genes [1, 3, 6].
The World Health Organization has declared antibiotic resistance in multi-resistant bacteria to be a public health threat, which will have a significant impact on global health, economy and morbidity [7].
Since critically ill neonates are more exposed to being colonized and infected by multi-resistant bacteria mainly due to invasive procedures and antibiotic use, protocols and strategies have been implemented in various neonatal intensive care units worldwide to prevent and eradicate such outbreaks, and its success rate depends on the adherence of the health personnel and the parents of the patients [7, 8].
2.1 Prevention and control measures for outbreaks and infections in neonatal intensive care units
There are several causes that have been investigated as contributing factors to the presence and spread of multi-resistant bacterial outbreaks in neonatal intensive care units [1, 3, 8, 9, 10].
Among the main ones, the following have been highlighted:
Use of powdered neonatal formulas for various patients.
Use of boiled water, which is not completely sterile.
Shared use of breast pumps among mothers of infants in the unit.
Inadequate disinfection of cribs, sinks, and boiled water reservoirs.
Inadequate hand washing, both by health personnel and parents of patients.
Ignorance or misapplication of contact isolation protocols in infected or colonized patients.
Inadequate cleaning and healing of peripheral or central catheters of hospitalized neonates.
Lack of routine microbiological studies in neonatal intensive care units.
Given the aforementioned causes, some prevention and control measures for outbreaks and nosocomial infections have been implemented. These measures focus on hygiene, timely identification of outbreaks, control of their transmission, and optimization of the proper and conscious use of antibiotics.
2.1.1 Hand hygiene
Hand washing is one of the most important measures to prevent the spread of multi-resistant bacteria. Correct hygiene must be carried out using the 12 steps and the five moments of hand washing established by the World Health Organization (Figures 1 and 2).
Figure 1.
0–11 steps of hand washing. Under authorization of the WHO [11].
Figure 2.
Five moments for hand hygiene. Under authorization of the WHO [12].
All hand hygiene steps must be performed by both the parents of the neonates, as well as the health and cleaning staff of the neonatal intensive care area.
In the authors experience, a handwashing checklist was implemented in their units (Table 1) this checklist that must be complied with by each one of the workers in the neonatology area, and patient visitors, together with the presence of a timer to verify that Hand hygiene lasts at least 40 seconds [1].
Removal of gown, jackets or coats
Removal of rings, watches or bracelets
Sleeve folding
Cap placement
Activation of the stopwatch
Performing the 12 steps of hand washing
Meet the five moments of hand washing
Table 1.
Handwashing checklist. Authorized by the authors [1].
2.1.2 Environmental cleaning, medical equipment, and contact isolation
Medium equipment or devices such as respirators or catheters must be used following strict hygiene measures and aseptic techniques for placement and maintenance. In addition, it is very important to carry out regular cleaning and disinfection with appropriate solutions.
In addition, when an outbreak or infection has been identified in a neonate, he or she should be placed in contact isolation to prevent the transmission and spread of the multiresistant bacteria. This not only implies the physical separation of infected neonates, but the use of individual rooms or cubicles within the infrastructure of the neonatology area.
Disinfectant solutions are used, both in liquid or vaporized form, or in cleaning cloths, containing 17% alcohol solutions, or 35% hydrogen peroxide, or sodium hypochlorite. Those are used for the disinfection of cribs, incubators, medical and nursing equipment, tables, and scales. It is essential that this solutions remains in contact for at least 3 minutes on the area to be disinfected to guarantee a higher success rate [1, 3, 5].
There are several investigations that show a greater advantage in disinfection when it is carried out by direct vaporization of the environment and infrastructure of the unit. The process is simpler, more effective, takes less time, and has a lower degree of toxicity and chemical irritation to the skin of cleaning personnel, health workers, and neonates [3].
2.1.3 Measures that should be implemented in patients in the neonatal intensive care unit
Taking into account that neonatal patients receive breast milk or formula, invasive measures and venous or arterial access are taken, prevention must be carried out in each of these edges to prevent the growth of outbreaks.
A very important measure in neonatal intensive care units is the disinfection and sterilization of the material with which the infant formula is prepared, or the instruments for extracting breast milk, being individualized for each mother of critical neonates. With the respective barrier measures, among which are gloves, gowns, hats and a mask [9, 13].
In addition, it is recommended to use purified water, preferably bottled, for the preparation of formulas; or the use of liquid formulas that are prepared in a sterile manner, discarding the leftovers after their use.
In invasive procedures such as the placement of central lines, venous or arterial access, as well as the disinfection of the entrances of said routes; prior disinfection with 2% chlorhexidine with 0.9% saline solution is recommended, which can be replaced by the use of chlorhexidine sachets [1, 3, 10].
In addition, for the entrances of intravenous devices, the use of caps containing antiseptic substances is recommended.
These infection control measures are very important, since superficial cleaning does not guarantee the eradication of biofilm particles, which can cause cross-transmission of multi-resistant bacteria, with consequent colonization and transmission [4, 9].
2.1.4 Control of visits and effective communication with the newborn’s family
Despite the fact that the accompaniment of the family is essential in the recovery of a newborn, it is important to implement restrictions on visits to patients with a more critical condition, since, coming from an environment outside the hospital, they may be carriers of pathogens that can potentially cause outbreaks or infections.
It is a very relevant factor to explain and guide them in a warm and safe way about hand hygiene before and after entering the unit. It must be done under supervision, complying with the hand washing checklist, and putting on gowns and biosecurity measures [9, 10].
2.2 Microbiological characteristics and rational use of antibiotics in neonates
The neonatal intensive care unit is a medical setting in which specialized care is provided to newborns who are premature or seriously ill. The vulnerability of these patients to infections and the importance of adequate treatment makes the rational use of antibiotics a fundamental aspect in clinical practice [8].
2.2.1 Predominant microorganisms
The neonatal intensive care unit is a conductive environment to the proliferation of bacteria, fungi, and other pathogens.
Some of the more common bacteria include Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp. In addition, fungi of the Candida species are an important cause of infections in neonates [1, 8].
2.2.2 Antimicrobial resistance
Frequent exposure to antibiotics in the neonatal intensive care unit has led to the development of antimicrobial resistance to pathogens. This complicates treatment and increases the morbidity of newborns [9, 10, 14].
The colonization of neonates with multi-resistant bacteria is a worrying issue for public health, not only because of the possibility of a serious nosocomial infection, but also because of the creation of reservoirs of multi-resistant bacteria and bacterial resistance genes.
Various mechanisms of bacterial resistance have been developed, such as the production of extended-spectrum beta-lactamases, and the production of carbapenemases. All this, coupled with poor control of antibiotic management, neonatal immunological immaturity, and invasive procedures in neonates, make the impact on prognosis, hospital stay, and hospital costs greater [1].
2.2.3 Empirical therapy and rational use of antibiotics
Early and accurate diagnosis of an infection is essential for the rational use of antibiotics. Appropriate microbiological and diagnostic tools such as blood cultures, cerebrospinal fluid analysis, and antibiotic susceptibility testing should be used [1, 15].
Since the results of culture results can take several days, it is common for empiric antibiotic therapy to be started. However, this therapy should be based on local knowledge of resistance patterns and adjusted based on culture results and susceptibility testing [1, 7, 15].
Antibiotics must be given for as long as necessary to treat the infection. As soon as possible, de-escalation should be considered, that is, adjusting the treatment according to the results of the cultures and the clinical stay of the patient, thus avoiding unnecessary and prolonged exposure to antibiotics [1, 7, 9].
2.3 Education and training of health personnel
The education of health personnel must include a solid understanding of antimicrobial resistance and its clinical implications.
Training should be carried out on adequate hygiene practices, such as correct hand washing, the correct use of personal protective equipment, and cleaning and disinfection of surfaces and equipment. In addition, they must be aware of infection control policies and protocols [1, 3].
Education and training should foster interdisciplinary collaboration in the neonatal intensive care unit. This implies effective communication between doctors, nurses, microbiologists and other health professionals involved in the care of newborns [9, 15].
2.4 Importance of epidemiological surveillance
Epidemiological surveillance refers to the systematic collection, analysis and interpretation of data related to the health of the population. In our context, their intervention in the neonatal intensive care unit implies constant monitoring of the appearance of infections and the identification of patterns to prevent the spread of multi-resistant bacteria [1, 6].
It plays a fundamental role in the prevention and control of outbreaks of multi-resistant bacteria. These outbreaks are a significant threat to the health of sick and premature newborns, and can have serious and even fatal consequences [1, 6].
2.4.1 Early surveillance of outbreaks and implementation of control measures
Early surveillance of outbreaks allows the detection of multi-resistant bacteria. By continuously monitoring infection data, unusual increases in infection incidence can be identified and preventative measures taken before it becomes uncontrollable [1, 2, 6].
In addition, through timely surveillance, control measures for the prevention and spread of outbreaks can be quickly implemented.
These measures may include the adoption of stricter hygiene practices, the promotion of vaccination, the optimization of the use of antibiotics and the segregation of infected patients [1, 2, 6].
It is essential to carry out microbiological studies, processing specific cultures of neonatal patients, and their environment, such as sinks, cribs, hands of medical and nursing staff, and boiled water reservoirs and formula cans [1, 4, 16].
2.4.2 Monitoring the effectiveness of interventions
The continuous monitoring of the established interventions allows tracking the results of the control measures, in this way it can be determined if they are having the desired impact in the reduction of outbreaks of multi-resistant bacteria. This provides an opportunity to adjust and improve prevention strategies [1, 3].
In addition to the detection of multi-resistant bacteria, epidemiological surveillance of the neonatal intensive care unit plays a key role in monitoring antimicrobial resistance. This helps identify patterns of resistance and guide the appropriate selection of antibiotics for the treatment of neonatal infections [1, 3, 10].
In the authors’ experience, a strategy to eradicate an outbreak of Carbapenemase-producing Klebsiella pneumoniae was implemented in the neonatology area of a hospital in Ecuador.
It was observed that, by implementing and educating about the handwashing checklist, a 99% adherence to the five moments and 12 steps of handwashing could be seen. This was applied both to medical personnel and to the relatives of the neonates who stayed with them, thus demonstrating that the main control measure was education for health personnel working in the neonatology area [1].
Several serial cultures were carried out, decreasing their positivity, noting in the long term that the establishment of the measures reduced the presence of the outbreak until its complete eradication after 1 year of follow-up [1].
Several similar studies carried out in Colombia, Italy, and Spain implemented a package of similar measures, with certain changes, such as daily bathing of patients with chlorhexidine gluconate, and monthly monitoring of the outbreak with cultures [1, 17].
In a neonatal intensive care unit in Australia, after presenting an outbreak of multi-resistant gram negative bacteria, the removal of sinks and a change in the neonatal bathing strategy were implemented as a strategy. They showed that the cessation of the daily bathing routine for neonates, and changing and cleaning the sinks consistently reduced the outbreak, emphasizing the need to control and treat water in neonatal units [6].
In a study carried out in Brazil, they observed that the extended use of antibiotics in neonatal patients was associated with the presence of multi-resistant bacteria, focusing on the rational use of antibiotics as a measure to reduce outbreaks in the neonatal intensive care unit [2].
In Malaysia, an outbreak of Acinetobacter baumanii was successfully eradicated from a neonatal intensive care unit. The researchers showed that poor hand washing, lack of disinfection of supplies and poor storage of breast milk and infant formulas were the source of colonization and the presence of the outbreak. They implemented a systematic check-up to control hand washing, sink cleaning, good management of breast milk storage, and control of neonatal hygiene, with which they managed to contain the outbreak [15].
In France, an outbreak of Enterobacter cloacae was investigated in a neonatal intensive care unit, implementing contact isolation measures, sterilization of breast milk pumps, reduction of the use of broad-spectrum empirical antibiotic therapy, and education of health personnel [9].
4. Challenges faced by neonatal intensive care units
Neonatal intensive care units face several challenges in the fight against multi-resistant bacteria due to the vulnerability of newborns and the complexity of the hospital environment. The most common challenges include:
Limited immunity: critically ill or premature infants in intensive care often have immature or weakened immune systems, making them more susceptible to bacterial infections, primarily nosocomial ones. In addition, they often require invasive procedures and broad-spectrum antimicrobial therapy, further increasing the risk of multidrug-resistant infections [10, 17].
Cross transmission: neonatal intensive care units are environments with a high density of patients and staff, which facilitates the transmission of multi-resistant bacteria between sick neonates. Germs can spread through direct or indirect contact, such as medical equipment, staff’s hands, the air, and water [3, 13].
Inappropriate use of antibiotics: the excessive or inappropriate use of antibiotics in neonatal intensive care units can favor the development and spread of multi-resistant bacteria. This can occur when antibiotics are prescribed without adequate assessment for infection or when broad-spectrum therapies are used without adequate monitoring [9, 14].
Diagnostic limitations: early and accurate identification of bacterial infections in newborns can be complicated due to the lack of specific symptoms and the difficulty in obtaining quality laboratory specimens. This can delay proper treatment and facilitate the spread of multi-resistant bacteria [4, 10].
Although the management of multi-resistant bacteria in the Pediatric Intensive Care area can be a complex challenge, it is possible to address it taking into account the premises of this chapter and applying them in the different areas of intensive care, not only neonatal, but also pediatric and adult.
The key is in the adoption of strict prevention measures, in order to promote a culture of health safety and health awareness in all health personnel, and the parents of newborns who are a key part in their recovery.
The multidisciplinary approach in the fight against multi-resistant bacteria in the pediatric intensive care unit must involve not only doctors and nurses, but also microbiologists, epidemiologists, and different public health coordination areas. This will allow you to create more effective strategies and with a greater focus.
Active surveillance of infections and outbreaks, continuous monitoring of bacterial resistance, and rational use of antibiotics are crucial measures to prevent the emergence and spread of multi-resistant bacteria. This involves systematic data collection and analysis, careful assessment of the need for antibiotics, selection of specific and targeted therapies for each patient and identified pathogen, optimal duration of treatment, as well as implementation of follow-up and feedback programs to assess the effectiveness of interventions.
Another important pillar is continuous education and training for staff on the best infection prevention and control practices. In addition to creating awareness in each of the importance of hand hygiene, rational use of antibiotics, early identification of outbreaks. A fundamental part of education is effective communication with parents, instructing them on biosafety standards when entering to see their children.
Continuous education, involving both family members and health personnel are very important and fundamental pillars to reduce the incidence of outbreaks and infections, and thus reduce their impact on the care units. Neonatal intensive care, and decrease neonatal mortality.
The authors thank their neonatal patients who tirelessly fight every day to get ahead.
We thank our families and neonatology for being passionate every day to give the best for the benefit of newborns.
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Written By
Santiago Garzón and Fernando Aguinaga
Submitted: 02 August 2023Reviewed: 27 September 2023Published: 07 November 2023
Open access peer-reviewed chapter
