FormalPara Key Summary Points

Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) infections represent potentially costly comorbidities, with rates of acquisition that vary widely between nations.

Articles described VAP rates in Gulf Cooperation Council member states that varied widely by nation and time, with multi-year studies suggesting a trend of decreasing VAP rates over the last 10–15 years.

The most commonly reported organisms associated with HAP/VAP infections were multidrug-resistant species in the genera Acinetobacter, Pseudomonas, and Klebsiella, although methicillin (meticillin)-resistant Staphylococcus aureus and Streptococcus pneumonia were also commonly identified.

The high frequency of treatment-resistant bacterial pathogens represents a challenge to further improvement in managing these infections.

Introduction

Hospital-acquired infections (HAIs), also referred to by the broader term of healthcare-associated infections, are typically defined as infections that occur during care in a hospital facility that were not present or incubating at the time of admission [1]. HAIs usually manifest ≥ 48 h after hospital admission and include infections that present after hospital discharge. Hospital-acquired pneumonia (HAP; pneumonia occurring ≥ 48 h after hospital admission) and ventilator-associated pneumonia (VAP; pneumonia occurring ≥ 48 h after endotracheal intubation) are among the most frequent types of HAI both in high-income and low-/middle-income countries [1, 2]. Use of the term HAP varies across guidelines and studies [2]; in this review, HAP encompasses any pneumonia occurring ≥ 48 h after hospital admission and therefore includes VAP as a subset.

In general, there is wide variation in VAP rates reported across studies due to a combination of factors, including country, intensive care unit (ICU) type, patient case-mix, and differing definitions of VAP [3, 4]. Surveillance of device-associated HAIs during 2012–2017 in ICUs across 45 countries of the International Nosocomial Infection Control Consortium [INICC; predominantly countries with developing economies, including Bahrain, Kuwait, Saudi Arabia, and the United Arab Emirates (UAE)] determined pooled mean VAP rates for 11 ICU types [5]. VAP rates ranged from 7.4 (surgical cardiothoracic ICUs) up to 17.7 per 1000 ventilator-days (medical cardiac ICUs), which were considerably higher than those reported in the USA.

The pathogens most frequently associated with VAP include Pseudomonas aeruginosa, Acinetobacter baumannii, Gram-negative bacilli of the Enterobacterales family (particularly Escherichia coli and Klebsiella pneumoniae), and Staphylococcus aureus [2, 3]. Antimicrobial resistance rates, including multidrug resistance among common HAP/VAP pathogens, are substantial. International surveillance data report methicillin (meticillin) resistance in approximately one half of S. aureus isolates, high rates of cefepime and piperacillin-tazobactam resistance in P. aeruginosa (up to 30%), and carbapenem resistance in > 50% of A. baumannii isolates [2]. Of further concern, multidrug resistant (MDR) pathogens pose a serious problem in Middle Eastern countries due to multiple predisposing factors, including antibiotic misuse and overuse, continuous population movement, and inadequate infection prevention and control strategies [6]. Other inherently MDR organisms as a result of extensive carbapenem use (namely Stenotrophomonas maltophilia) are also encountered in critical care units. Furthermore, apart from bacteria, certain fungi (in particular Candida auris) can be challenging for hospitals and clinicians in view of MDR and their propensity to spread, persist in the hospital environment, and cause outbreaks in ICUs that are difficult to treat [7, 8].

Infection control and surveillance in Gulf Cooperation Council (GCC) countries is coordinated by the GCC Centre for Infection Control (GCC-CIC) [9]. In addition to providing evidence-based guidelines for infection control practices, the GCC-CIC conducts educational and training activities for personnel working in infection prevention and control [9]. Current standards for respiratory therapy procedures are contained in the GCC Infection Prevention and Control Manual, including detailed protocols for the setup and maintenance of mechanical ventilation circuits and artificial airways, specimen collection, personal protective equipment, and hand hygiene [10]. However, further initiatives and more extensive participation in training activities for infection surveillance and data management are needed, and there is not yet a comprehensive and integrated system in place for collecting and compiling data from hospitals throughout the region [9].

Although all GCC countries are classified as high-income, their economies are still developing, and their healthcare systems face many of the challenges common to other developing nations [9, 11]. Subsequently, this narrative review was undertaken to summarize available data related to the incidence and associated organisms of HAP and VAP in hospitals throughout GCC countries, with a view to identifying unmet medical needs and future challenges for the management of HAP/VAP in the region.

Methods

A PubMed database search was carried out on 13 November 2021 using the search terms: “pneumonia, ventilator associated”[MeSH Terms] OR (pneumonia AND “ventilator associated”) OR “ventilator-associated pneumonia” OR (ventilat* AND associated AND pneumonia) OR ((device OR catheter) AND associated AND pneumonia) OR “healthcare-associated pneumonia”[MeSH Terms] OR (“healthcare associated” AND pneumonia) OR “healthcare-associated pneumonia” OR (healthcare AND associated AND pneumonia) OR “hospital-acquired pneumonia” OR (“hospital acquired” AND pneumonia) OR (nosocom* AND pneumonia) AND (Gulf OR Bahrain OR Kuwait OR Oman OR Qatar OR “Saudi Arabia” OR “United Arab Emirates” OR UAE) NOT Review[publication type]. The search was additionally limited to English-language articles published in the preceding 10 years.

Search results were reviewed by the authors to identify articles reporting original data related to HAP or VAP in patients of any age; articles that did not report HAP or VAP data specific to a GCC country were excluded. Search results were initially screened for relevance on the basis of the title and abstract, then full copies of each identified article were further reviewed for relevance.

This article is based on previously conducted studies and does not contain any new studies with human participants performed by any of the authors.

Results

Based on title and abstract, 57 articles were identified for full-text review. Among the full-text articles assessed, 41 were ultimately selected for potential inclusion in the review (Fig. 1), including studies conducted in Saudi Arabia (n = 32), Kuwait (n = 4), Qatar (n = 2), Oman (n = 1), UAE (n = 1), and Bahrain, Oman, and Saudi Arabia (n = 1). The majority of identified studies focused on VAP, either exclusively or in the context of HAIs, with only 2 publications [12, 13] focusing on HAP; thus, the majority of the discussion in the current review focuses on VAP.

Fig. 1
figure 1

Selection process. GCC Gulf Cooperation Council, HAP hospital-associated pneumonia, VAP ventilator-associated pneumonia

Full size image

VAP Rates

Annual VAP rates varied widely between studies and over time (Fig. 2). In the studies that reported data for multiple years, there was a general trend for reduced VAP rates over time. In support of this observation, a longitudinal study (2008–2013) conducted in Bahrain, Oman, and Saudi Arabia showed a general trend for reduced ICU-associated VAP rates over time (Fig. 3A) [9]. A number of time-series analyses reported reduced VAP rates with VAP prevention bundles [9, 14,15,16,17,18,19]. Studies identified a need for further study of prevention and intervention programs, evidence-based treatment guidelines, and increased VAP-related education activities for staff to ensure that protocols are properly implemented [20,21,22].

Fig. 2
figure 2

VAP rates in adult ICUs across GCC countries as reported by various studies included in this review [9, 14, 17,18,19, 23, 29, 32, 34]. The inset shows ICU type for data from work by Ali et al. (2016), which was the only included study describing rates in a single GCC nation, Qatar [23]. GCC Gulf Cooperation Council, ICU intensive care unit, VAP ventilator-associated pneumonia

Full size image
Fig. 3
figure 3

VAP rates across ICUs in Bahrain, Oman, and Saudi Arabia, 2008–2013, as reported by El-Saed 2016 [9] A by year and B by ICU type. Note that, for panel B, the VAP rate for trauma ICUs is reported for the time period 2010–2013 (not 2008–2013). ICU intensive care unit, VAP ventilator-associated pneumonia

Full size image

One study from Qatar from 2010 to 2012 that analyzed data by ICU type demonstrated higher VAP rates within trauma ICUs than within medical or surgical ICUs (Fig. 2, inset) [23]. In contrast, a study from Bahrain, Oman, and Saudi Arabia from 2008 to 2013 reported higher VAP rates within medical/surgical ICUs than trauma ICUs, although data from trauma ICUs were collected only from 2010 to 2013 (Fig. 3B) [9].

Infective Agents and Antimicrobial Resistance

Table 1 summarizes the reported associated organisms of HAP/VAP and antimicrobial resistance data. It is noteworthy that isolation of organisms from respiratory samples is not evidence that they are causative of the HAP/VAP unless they are isolated from both the blood culture and respiratory samples at the same time, which is uncommon. Thus, for the purposes of this review, we refer to organisms as being associated with VAP.

Table 1 HAP-/VAP-associated organisms and antimicrobial resistance
Full size table

Gram-negative bacteria were the most commonly reported organisms overall, including Acinetobacter species (particularly A. baumannii), Pseudomonas species (particularly P. aeruginosa), and Klebsiella species (particularly K. pneumoniae). Gram-positive bacteria included methicillin-resistant S. aureus and Streptococcus pneumoniae. Other pathogens of note were S. maltophilia, which is an important nosocomial pathogen in children in Saudi Arabia [24], and carbapenem-resistant Providencia stuartii [12] (Table 1).

Among studies that reported antimicrobial resistance, rates of resistance varied widely. Multidrug resistance (i.e., resistance to ≥ 1 agent in ≥ 3 antimicrobial classes) was frequently reported among A. baumannii, K. pneumoniae, E. coli, P. aeruginosa, and S. aureus isolates [23, 25,26,27,28,29,30]; vancomycin-resistant Enterococcus [26] and MDR Enterococcus species [26, 30] were rarely reported. A study in Saudi Arabia conducted from 2015 to 2018 reported carbapenem-resistant Gram-negative organisms in 25% of all VAP cases [31], while another study from Saudi Arabia from 2016 to 2019 reported 19% [25]. Two studies in Kuwait, one in Qatar, and one in Oman reported extended-spectrum beta-lactamase K. pneumoniae (17–32%), E. coli (75%), or Enterobacterales isolates (24%) [23, 29, 30, 32]. From 2004 to 2009, a tertiary care hospital in Riyadh reported 60–89% resistance to all tested antimicrobials for Acinetobacter species and 13–31% for P. aeruginosa; Klebsiella species were fully resistant to ampicillin and 0–13% were resistant to other tested antimicrobials [27].

Genotype data were sparse in the reviewed studies. One Saudi Arabian study that analyzed 12 extensively drug-resistant (XDR; defined as resistant to at least four classes of antimicrobials, including carbapenems) A. baumannii isolates from patients with VAP reported that none of the 12 isolates harbored a class B carbapenemase gene; class A carbapenemase blaGES was detected in 2 out of 12 isolates. Insertion sequence ISAba1 was detected in 5 out of 12 isolates, all isolates harbored Acinetobacter-derived cephalosporinases, and all isolates were carbapenem resistance–associated OM protein negative (i.e., had no evidence of efflux-mediated carbapenemase resistance) [33]. In another study in Saudi Arabia in patients with carbapenem-resistant infections, OXA-48 was the predominant carbapenemase in ≥ 68% of patients [13].

Ventilator Utilization Ratios

Table 2 shows reported VAP rates and ventilator utilization ratios, which varied widely over time between ICU type and between studies. A study in Kuwaiti patients from 2013 to 2015 reported a utilization rate of 0.9 for adult medical/surgical ICUs and 0.1 for adult coronary ICUs [34]. Another study in Saudi Arabia reported utilization rates of 0.7, 0.6, and 0.2 for adult medical, surgical, and cardiac ICUs, respectively [17], while a study from 2008 to 2013 conducted in Bahrain, Oman, and Saudi Arabia reported rates of 0.5–0.6 across adult ICUs [9]. There was no discernable trend over time in that study, with reported utilization ratios of 0.5 in 2008, 0.6 in 2012, and 0.5 in 2013 [9]. Another study in Saudi Arabia reported a decrease in utilization rates from 0.7 in 2003 to 0.5 in 2009 [14], while a study in Kuwait reported a rate increase from 0.7 to 0.8 in 2014 to 2015 [16].

Table 2 Reported VAP rates and ventilator utilization ratios—all ICU types
Full size table

Discussion

This narrative review was undertaken to summarize available data related to the incidence and causative organisms of HAP and VAP in hospitals throughout GCC countries. Data from multi-year studies suggest that VAP rates have generally decreased over time in GCC countries [16, 18, 19, 23, 32]. Although time-series analyses suggest that VAP prevention bundles reduce VAP rates [9, 14,15,16,17,18,19], the contribution of individual components is somewhat unclear. A recent review found no high-level evidence to support an association between ventilator bundle implementation and reduced ventilator-associated event (VAE) risk [3]. Indeed, findings suggest that chlorhexidine and stress ulcer prophylaxis may actually increase VAE risk, while reduced mechanical ventilation duration will likely reduce VAE risk [3]. In controlled studies, a significant impact of probiotics on VAP rate has not been observed. These studies include a randomized controlled study carried out in ICUs across North America and Saudi Arabia to assess the effect of the probiotic Lactobacillus rhamnosus GG on VAP development in critically ill patients. Results of the study showed no significant difference in VAP incidence between the probiotic and placebo groups, or for any of the other prespecified outcomes [35].

Additionally, our literature review suggests that the most common organisms associated with VAP in GCC countries were Gram-negative bacteria, particularly Acinetobacter species, Pseudomonas species, and Klebsiella species, as well as Enterococcus species, with MDR reported in many studies. The types of organisms associated with HAP/VAP and the proportions of positive isolates were similar between the countries studied (Saudi Arabia, Kuwait, and Oman; Qatar; or UAE). E. coli and P. aeruginosa were present in up to approximately 40% of isolates, and A. baumannii and K. pneumoniae were isolated from > 50% of isolates in at least one of the included studies.

Our analysis also found a wide range of ventilator utilization ratios, with higher ratios increasing the likelihood of developing VAP. Thus, ventilator utilization ratio may be a useful outcome measure in VAP prevention studies [18]. However, ventilator utilization ratios are necessarily higher in certain patient populations (e.g., very-low-birth-weight infants, patients with chronic obstructive pulmonary disease); therefore, it may be misleading to compare ratios across different hospitals/facilities due to differences in patient populations [36].

Infection prevention programs commonly incorporate multimodal horizontal strategies that aim to reduce risk from all nosocomial pathogens, such as hand hygiene protocols, environmental disinfection, and prevention bundles [37, 38]. Internationally, many organizations have developed VAP prevention guidelines and tools, and VAP bundles have been widely implemented in hospitals [39,40,41]. While infection control and surveillance in GCC countries is coordinated by the GCC-CIC and evidence-based guidelines for infection control practices have been provided by the organization [9], local differences in antimicrobial policies and antimicrobial stewardship programs may exist [42]. Substantial variability has been noted among the VAP bundles adopted by different hospitals in other countries, although utilized components frequently include head-of-bed elevation by 30–45°, daily interruption of sedation and assessment of readiness to extubate, use of endotracheal tubes with subglottic secretion drainage ports, and avoidance of ventilator circuit changes unless visible soiling is present [40, 41]. The INICC Multidimensional Approach for VAP rate reduction incorporates multiple strategies: a VAP prevention bundle; education; outcome and process surveillance; and provision of feedback related to VAP rates, VAP consequences, and performance [34]. VAP data also constitute part of the performance dashboard of hospital infection prevention and control committees.

A limitation of this analysis is that the data were compiled from different and diverse healthcare organizations and laboratories, which have variations in definitions and diagnostic limitations, as well as differing methodologies and technologies used in the detection, speciation, and susceptibility testing of isolated organisms from patients with VAP [3]. An illustration of this variation is the implementation of the VAE model by the US National Healthcare Safety Network (NHSN) in 2013 [43], which resulted in a large difference in reported VAP incidences between the USA and Europe [3]. Further evidence of these variations and the limitations they place on these data analyses was found in the surveillance of device-associated HAIs in ICUs across the INICC, which showed that pooled mean VAP rates ranged from 7.4 to 17.7 per 1000 ventilator-days depending on ICU type. These were considerably higher than 2012/2013 US NHSN pooled means (0.7–3.6 per 1000 ventilator-days) [5]. Accordingly, comparison of national VAP rates with the USA has been cautioned against due to varying classifications. Also, studies evaluating the effect of prevention bundles on VAP rates may be difficult to generalize to the overall population. This paper is a review of different retrospective studies, and thus, generalization of the impact of prevention bundles is difficult due to missing data since, generally, most papers were not studying prevention bundles and a few studies correlated bundle implementation with VAP rates. Another limitation of the current review is that all of the included studies were conducted before the onset of the coronavirus disease 2019 (COVID-19) pandemic and, therefore, do not take into consideration the likely increases in VAP rates [44].

Conclusions

Although VAP rates have generally decreased over time in GCC countries, VAP and associated MDR organisms remain a burden. Overall, there is a need for further research, including prospective, randomized, multicenter studies carried out in the Gulf Region, to assess the diagnosis, prevention, and treatment of VAP. Research should also include details of bundles used to reduce VAP incidence, protocols of care, and toolkits used to carry out root-cause analysis on VAP infections. Furthermore, it would be useful to have an overarching multi-Gulf center surveillance program to continually monitor the incidence and prevalence of VAP and HAP and, indeed, other HAIs across the GCC countries.