Characterization of Bacteria Community Composition and Antimicrobial Susceptibility

Profile in the Intensive Care Unit of a Community Hospital in Bermuda

Introduction

ICU patients have risk factors for healthcare associated infections (HAI) due to their underlying
conditions, impaired immunity and exposure to multiple invasive devices [3]. The ICU is considered a
source for the dissemination of multidrug-resistant organisms (MDROs), primarily due to the extensive
antimicrobial use in that setting which promotes a selection pressure promoting the emergence of
MDROs [4]. The two predominant MDR Gram positive organisms responsible for causing HAIs are
methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE). MRSA
has many routes of transmission including formite contacts or the hands of colonized healthcare
professionals. The Gram–negative organisms Pseudomonas aeruginosa, Acinetobacter baumannii,
Klebsiella pneumoniae and Sterntrophomonas maltophilia can also become MDRO and cause HAI,
especially in an ICU setting. It has been reported that room occupation by a patient with VRE, MRSA,
Clostridium difficile or Acinetobacter baumannii infection, increases the risk for subsequent patients
developing HAIs with these organisms, suggesting that the organisms remained in the environment
despite room cleaning between patients [5]. The presence of biofilms may be a contributing factor for
the persistence of environmental contamination. Biofilms can protect incorporated bacteria from both
desiccation and the action of cleaning and disinfecting agents.

Abstract

Objective: This study was undertaken to determine the presence of multidrugresistant (MDR)
pathogenic bacteria in the environment of the Intensive Care Unit in a community hospital in Bermuda.

Methods: Twenty six environmental swabs taken from specific areas such as door handles, sinks,
cupboards, drip stands, bed railings, work stations, computer keyboards and telephones were obtained
for the study. Standard Microbiological methods using Clinical Laboratory Standards Institute (CLSI) were
used in the study. Identification and susceptibility testing for all isolates were carried out using the Vitek
II automated system (BioMerieux, Inc., Durham, NC).

Results: No multi-drug–resistant organisms were isolated from the ICU environment. The majority of the
organisms isolated were non-pathogenic Grampositive cocci such as coagulase negative Staphylococcus,
Micrococcus spp and Dermacoccus spp. Opportunistic pathogenic Gram-negative bacteria such as
Pseudomonas aeruginosa, Acinetobacter hemolyticus and Klebsiella oxytoca were detected and were
relatively susceptible to antimicrobial agents. In addition, Gram-negative organisms such as
Brevundimons diminuta and Parococcus yeei were isolated from the environment. However, these
organisms are usually not pathogenic.

Conclusion: Good compliance with Infection Prevention and Control measures as well as antimicrobial
stewardship are important in preventing hospital acquired infections (HAI) including those caused by
MDR organisms especially in an ICU setting.

Keywords

ICU; Bacteria community; Antibiotic susceptibility; Multidrug resistance

References

1. Salgado CD, O’ Grady N, Farr BM (2005) Prevention and control of antimicrobial resistant
infections in intensive care patients. Crit Care Med 33: 2373-2382.

2. De Kraker M, Wolkewitz M, Davey P, Koller W, Berger J, et al. (2011) Burden of antimicrobial

resistance in European hospitals: excess mortality and length of hospital stay associated with
bloodstream infections due to Escherichia coli resistant to third generation cephalosporins. J
Antimicrobial Chemother 66: 398-407.

3. Marwick C, Davey P (2009) Care bundles: the holy grail of infections risk management in
hospitals? Curr Opin Infect Dis 22: 364-369.

4. Nicholoson AM, Ledgister S, Williams T, Robinson S, Gayle P, et al. (2009) Distribution of

nosocomial organisms and their resistance patterns in the intensive care unit of the West Indies,
Kingston, Jamaica. West Indian Med J
Patients suffering from psychological impairments following critical illness are in need of information

Abstract

Background

Because critical illness survivors frequently experience several long-term psychological impairments
altering quality of life after ICU, there is a trend towards increasing follow-up care, mainly via ICU follow-
up clinics. Despite these and other initiatives, understanding of patient’s post-ICU needs to help them
cope with their problems and subsequently improve quality of life is largely lacking. Our aim was
therefore to assess the needs, expectations and wishes in ICU survivors to receive information with the
purpose to help them better grasp ICU treatment. In addition, we assessed the perceived burden of
psychological trauma after ICU treatment and the health-related quality of life (HRQoL) up to 2.5 years
after ICU discharge.

Methods

In a multicentre, retrospective cross-sectional cohort study, the needs and preferred intervention
methods were assessed using a self-composed inventory in adult mechanically ventilated ICU survivors
(n = 43). Additionally, the Impact of Event Scale Revised, the Beck Depression Inventory, the EuroQol-
5D-5L, and the Short-Form 12 were used to assess psychological burden and HRQoL.

Results

A substantial proportion of all ICU survivors (59%, 95% CI 44% to 74%) suffered from psychological
impairments after ICU treatment. Seventy-five percent of these patients expressed a wish to receive
information, but only 36% desired to receive this information using a commonly used information
brochure. In contrast, 71% of these patients had a wish to receive information using a video film/VR.
Furthermore, only 33% of these patients was satisfied with the information provided by their treating
hospital. Patients with psychological PICS reported a worse HRQoL as compared to a normative Dutch
sample (P < 0.001) and as compared to patients without psychological PICS (P < 0.01).

Conclusions

In a Dutch cohort of critical illness survivors, a substantial part of ICU survivors suffer from psychological
impairments, such as PTSD and depression, which was associated with a worse HRQoL. These patients
are in need of information, have no desire using an information brochure, but are willing to receive
information using a video film/virtual reality module. These results support the exploration of such an
intervention.

Discussion

In the current study, we investigated whether the needs, expectations and wishes of patients were met
using the commonly used information brochure or whether patients preferred alternative delivering
methods to better grasp ICU treatment. In addition, we assessed the prevalence of psychological
impairments, the HRQoL and its association in a cohort of ICU survivors. Our data underscores that
psychological post-ICU sequelae, such as PTSD and depression, are a major clinical concern that may
persist for several years after ICU discharge and is associated with a considerable decrease in HRQoL.
Before routine follow-up of ICU-patients with such chronic conditions can be successful, it is important
to focus on the unmet healthcare needs of these patients. The current results clearly demonstrate that
patients suffering from psychological PICS have a self-reported unmet healthcare need of information
about their treatment. Subsequently, they are more interested in receiving digital information about
their ICU stay and treatment using a video film or VR compared to the currently accepted hardcopy
information brochure. This is the first study that demonstrated the patient’s wish for information
regarding ICU treatment and that a video or VR film might be a valuable adjunct. Apart from these
findings, the combination of questionnaires in the current study, which enables patients to give voice to
their experiences from 1 month to 2.5 years after ICU discharge, is a novel feature of self-reported
unmet healthcare needs. This adds to our understanding on how patients make sense of what has
happened to them and what they need to confront their fear after ICU-related trauma. Moreover, the
current cohort demonstrated that the prevalence of psychological PICS persists over time, up to 2.5 
years. This is in line with recent findings by Bienvenu et al. demonstrating that symptoms of anxiety,
depression and/or PTSD are common in the first 5 years after critical illness and has a similar incidence
over time. Our findings go beyond describing the incidence of PICS in our cohort but clearly give a
patient’s opinion on the preference of needs and wishes on post-ICU interventions. To date, knowledge
about the needs of patients suffering from PICS are scarce [33], and an effective treatment and thereby
a uniform aftercare protocol is missing for patients suffering from PICS. Our findings can therefore be
used to develop new treatment strategies, which can be implemented in an aftercare protocol in order
to ameliorate the HRQoL of these patients.

A recent survey of ICUs in the Netherlands demonstrated that the majority of ICU’s evaluate health
status and restrictions in functioning after ICU treatment [19]. Hence, 61% of the hospitals has or
currently is developing ICU follow-up care. There is a high probability that this number is even higher
because the survey was performed in 2014. This percentage is in accordance to the situation in the UK
and the USA. To date, no study has identified generalizable mechanisms by which post-ICU programs
could systematically treat psychological sequelae. It is therefore not surprising that several interventions
like ICU diaries [14, 17], ICU follow-up clinics [13, 34] or a primary care-focused team-based intervention
[16] did not have a significant effect to improve or prevent the psychological burden nor improving
health-related quality of life. A recent study by Heydon et al. demonstrated that patients with
psychological PICS related impairments identify these complaints as the most important area where
they want support in [35]. Additionally, psychological PICS is referred to as the most important
component of patient-reported unacceptable outcome by a recent study by Kerckhoffs et al. [7]. We
confirm these findings by demonstrating that PTSD and depression are both associated with a
considerable decrease in quality of life and that patients with psychological PICS have a worse quality of
life compared to the general Dutch population in contrast with patients without psychological PICS. This
is in line with a previous study by Wang et al., who demonstrated that the comorbidity of psychiatric
symptoms is associated with a worse quality of life [33]. To improve the success of post-ICU clinics,
treatment of psychological sequelae is critical to improve HRQoL. Additionally, our data suggest that
mental health is a more important contributing factor to decreased health-related quality of life
compared to the physical component. The mental health-related quality of life (MCS12) was decreased
in patients with psychological PICS, whereas the physical health-related quality of life (PSC12) was
comparable for patients with and without psychological PICS.

Conclusions

In a cohort of critical illness survivors, patient suffering from psychological PICS are in need of
information, have no desire using an information brochure but are willing to receive information via
digital content such as a video film/VR. Conceptualizing patient experiences and treatment
understanding might therefore be a well-appreciated new strategy to help patients cope with there
(delusional) memories, problems and questions. These results lay the groundwork for developing such
interventions to be tested in post-ICU programs and to determine whether mental health can be
improved.

References

1. Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis
and septic shock among critically ill patients in Australia and New Zealand, 2000-2012.
2. Oeyen SG, Vandijck DM, Benoit DD, Annemans L, Decruyenaere JM. Quality of life after
intensive care
3. Needham DM, Davidson J, Cohen H, Hopkins RO, Weinert C, Wunsch H, et al. Improving
long-term outcomes after discharge from intensive care unit: report from a stakeholders'
conference. Crit Care Med. 2012
4. Herridge MS, Tansey CM, Matte A, Tomlinson G, Diaz-Granados N, Cooper A, et al.
Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med.
2011;364(14):1293–304.matic review of the literature. Crit Care Med.
Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-
regression analysis

Abstract

Background

Our recent meta-analysis indicated that vitamin C may shorten the length of ICU stay and the duration
of mechanical ventilation. Here we analyze modification of the vitamin C effect on ventilation time, by
the control group ventilation time (which we used as a proxy for severity of disease in the patients of
each trial).

Methods

We searched MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials and reference
lists of relevant publications. We included controlled trials in which the administration of vitamin C was
the only difference between the study groups. We did not limit our search to randomized trials and did
not require placebo control. We included all doses and all durations of vitamin C administration. One
author extracted study characteristics and outcomes from the trial reports and entered the data in a
spreadsheet. Both authors checked the data entered against the original reports. We used meta-
regression to examine whether the vitamin C effect on ventilation time depends on the duration of
ventilation in the control group.

Results

We identified nine potentially eligible trials, eight of which were included in the meta-analysis. We
pooled the results of the eight trials, including 685 patients in total, and found that vitamin C shortened
the length of mechanical ventilation on average by 14% (P = 0.00001). However, there was significant
heterogeneity in the effect of vitamin C between the trials. Heterogeneity was fully explained by the
ventilation time in the untreated control group. Vitamin C was most beneficial for patients with the
longest ventilation, corresponding to the most severely ill patients. In five trials including 471 patients
requiring ventilation for over 10 h, a dosage of 1–6 g/day of vitamin C shortened ventilation time on
average by 25% (P < 0.0001).

Conclusions

We found strong evidence that vitamin C shortens the duration of mechanical ventilation, but the
magnitude of the effect seems to depend on the duration of ventilation in the untreated control group.
The level of baseline illness severity should be considered in further research. Different doses should be
compared directly in future trials.

Discussion

There is significant variation in the severity of disease in patients who are mechanically ventilated. One
measure of severity is the mechanical ventilation time required by the patient, which we used as a proxy
for severity. In this study, we found that the duration of ventilation in the untreated control group
explained most of the variation in the reported effects of vitamin C on the mechanical ventilation time.
In the standard meta-analysis, there is high-level heterogeneity with I2 = 83% (Fig. 3), whereas in the
meta-regression of the vitamin C effect by the control group duration of ventilation, the residual
heterogeneity is small with I2 = 12%

Some of the included trials examined elective surgical patients. These patients are not usually critically
ill; however, as a result of their surgery, they are routinely ventilated in the ICU for a period of time. In
the meta-regression, such patients are located on the left-hand side of Fig. 4 which means that the
analysis takes into account the low level of illness severity. In contrast, the inclusion of patients with less
severe disease in the standard meta-analysis decreases the average effect of vitamin C, so that the
greater effect on the sicker patients is masked (Fig. 3).

The substantial benefit observed in the Tanaka [17] trial seems to be explained by the particularly long
mechanical ventilation in the untreated control patients (which reflects the greater illness severity),
rather than the particularly high vitamin C dosage of 90 g/day in that trial. All the other trials used 6 
g/day or less, but there is no evidence that the benefit was less than in the Tanaka trial when taking into
account the ventilation time in the untreated control group (Fig. 4). There are a few reports of deaths
caused by intravenous vitamin C in doses of 80 to 224 g/day [32, 33]. Therefore, the interpretation that
the benefit in the Tanaka trial may be caused by the type of patients and not by the very high vitamin C
dose is important for planning further trials.

Our previous analysis of the length of ICU stay also found that the effect of vitamin C appeared greater
for the sicker patients. The length of ICU stay was reduced by 10.1% (P = 0.0001) in patients who
required an ICU stay of 3 days or longer, but by just 5.7% (P = 0.03) in those who needed only 1–2 days in
the ICU [1]

The substantial benefit observed in the Tanaka [17] trial seems to be explained by the particularly long
mechanical ventilation in the untreated control patients (which reflects the greater illness severity),
rather than the particularly high vitamin C dosage of 90 g/day in that trial. All the other trials used 6 
g/day or less, but there is no evidence that the benefit was less than in the Tanaka trial when taking into
account the ventilation time in the untreated control group (Fig. 4). There are a few reports of deaths
caused by intravenous vitamin C in doses of 80 to 224 g/day [32, 33]. Therefore, the interpretation that
the benefit in the Tanaka trial may be caused by the type of patients and not by the very high vitamin C
dose is important for planning further trials.

Our previous analysis of the length of ICU stay also found that the effect of vitamin C appeared greater
for the sicker patients. The length of ICU stay was reduced by 10.1% (P = 0.0001) in patients who
required an ICU stay of 3 days or longer, but by just 5.7% (P = 0.03) in those who needed only 1–2 days in
the ICU [1].

There are also other findings that are consistent with vitamin C having a greater effect on patients with
more severe medical conditions. A meta-analysis of vitamin C effect on exercise-induced
bronchoconstriction found that vitamin C halved FEV1 decline caused by exercise [34]. The constant
relative effect indicates that the absolute effect was greatest for patients who had the greatest
bronchoconstriction in the exercise test. Finally, a trial with common cold patients indicated that the
bronchodilatory effect of vitamin C was most beneficial for those with the greatest bronchial
hypersensitivity to histamine [35, 36].

There is much evidence indicating that vitamins C and E have an interaction in vitro and in vivo
[37,38,39,40,41], and three trials have examined the effect of the combination of vitamins C and E on
the duration of mechanical ventilation [29,30,31]. The reported effects from the three trials are largely
consistent with the meta-regression model based on the eight trials using vitamin C alone (Fig. 5),
though the confidence interval of the Nathens et al. trial does not cross the regression line. Thus, the
statistically significant benefit observed in each of these three trials might be explained by the long
ventilation time in the control groups, indicating greater severity of illness in the patients, rather than by
the addition of vitamin E to the intervention. To test the possible additional benefit of vitamin E over
vitamin C would require 2 × 2 factorial trials.

Although our meta-regression analysis by the ventilation time in the control group explains the
heterogeneity in the published trials, it seems evident that other variables influence the effects of
vitamin C. For example, there are indications that treatment effects can differ between less and more
developed countries. Panagiotou et al. identified several studies that reported greater treatment effects
in less developed countries than in more developed countries [42]. Although methodological variations
may explain some of the differences, there can also be genuine treatment differences between
substantially different cultures, since wealth is strongly correlated with life-style factors including
nutrition and with differences in hospital treatments. Previously, vitamin C was found to prevent post-
operative atrial fibrillation in non-US trials, but not in US-based trials [43], which may also indicate that
the effects of vitamin C can depend on cultural context. Thus, although the fit of the meta-regression
line in Fig. 4 is good, the findings should not be extrapolated directly to other contexts.

Two recent meta-analyses concluded that vitamin C is not beneficial for critically ill patients [44, 45],
whereas a third concluded that vitamin C was beneficial for sepsis patients [46]. However, all three
meta-analyses included studies that administered vitamin C in combination with numerous other
substances, such as vitamins A, B, and E, selenium, and zinc [47,48,49]. Such trials do not test the
specific effect of vitamin C. The other substances can have negative or positive effects, and they can also
modify the effect of vitamin C. The three meta-analyses also had statistical shortcomings [47,48,49]. Our
current meta-analysis was restricted to trials that tested vitamin C alone. A fourth recent meta-analysis
concluded that vitamin C shortens ventilation time in cardiac surgery patients [50]; however, the study
was shown to contain several substantial statistical errors [51].

In systematic reviews, one potential concern is publication bias, in that negative trials may remain
unpublished. However, publication bias cannot realistically generate the close association shown in Fig.
4. To explain this association by publication bias would require that positive studies with less ill patients
remain unpublished, and negative studies with severely ill patients also remain unpublished. Five trials
did not use an explicit placebo [12,13,14,15, 17], but we do not consider that the lack of placebo
undermines the validity of those trials, since ICU patients receive numerous treatments and it is unlikely
that one additional tablet or infusion would cause a substantial placebo effect for ventilated patients.
The lack of a placebo may cause bias in research on subjective outcomes, but less so on objective
outcomes [52]. Thus, it is unlikely to bias studies with outcomes such as the duration of mechanical
ventilation.

Conclusions

It may not be worthwhile to carry out further research on the effects of vitamin C on mechanical
ventilation for patient groups that require on average less than 10 h of ventilation. The level of sickness
severity should be taken into account in future studies, for example, by evaluating prognostic scores at
the start of the trial. Our analysis did not find differences between oral and intravenous vitamin C, but
oral administration is rarely an option for the sickest patients, for whom the effects of vitamin C appear
greatest. Our analysis is not informative about the optimal dosage of vitamin C. Future trials should
directly compare different dosage levels.

Availability of data and materials

Descriptions of the included trials, and the risk of bias assessment, and the analyzed data are available
as Additional files 1 and 2.

References

1. Hemilä H, Chalker E. Vitamin C can shorten the length of stay in the ICU: a meta-analysis.
Nutrients. 2019;11:708. https://doi.org/10.3390/nu11040708.
2. Long CL, Maull KI, Krishnan RS, Laws HL, Geiger JW, Borghesi L, Franks W, Lawson TC,
Sauberlich HE. Ascorbic acid dynamics in the seriously ill and injured. J Surg Res.
2003;109:144–8. https://doi.org/10.1016/S0022-4804(02)00083
3. Rümelin A, Jaehde U, Kerz T, Roth W, Krämer M, Fauth U. Early postoperative substitution
procedure of the antioxidant ascorbic acid. J Nutr Biochem. 2005;16:104–8.
https://doi.org/10.1016/j.jnutbio.2004.10.005.
4. Rümelin A, Humbert T, Lühker O, Drescher A, Fauth U. Metabolic clearance of the
antioxidant ascorbic acid in surgical patients. J Surg Res. 2005;129:46–51.
https://doi.org/10.1016/j.jss.2005.03.017