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Health care–associated and hospital-acquired infections are two entities associated with increased morbidity and mortality. They are highly costly and constitute a great burden to the health care system. Vitamin D deficiency (< 20 ng/ml) is prevalent and may be a key contributor to both acute and chronic ill health. Vitamin D deficiency is associated with decreased innate immunity and increased risk for infections. Vitamin D can positively influence a wide variety of microbial infections. Herein we discuss hospital-acquired infections, such as pneumonia, bacteremias, urinary tract and surgical site infections, and the potential role vitamin D may play in ameliorating them. We also discuss how vitamin D might positively influence these infections and help contain health care costs. Pending further studies, we think it is prudent to check vitamin D status at hospital admission and to take immediate steps to address existing insufficient 25-hydroxyvitamin D levels.
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Vitamin Ds potential to reduce
the risk of hospital-acquired infections
Dima A. Youssef,
1,
* Tamra Ranasinghe,
2
William B. Grant
3
and Alan N. Peiris
4
1
Department of Internal Medicine; Division of Infectious Diseases; East Tennessee State University; Johnson City, TN USA;
2
Research Associate; Jacksonville, FL;
3
Sunlight, Nutrition; and Health Research Center; San Francisco, CA USA;
4
Department of Medicine; East Tennessee State University; Johnson City, TN USA
Keywords: vitamin D, infections, antimicrobials, hospital-acquired infections, nosocomial infections, economic burden, deficiency
Health careassociated and hospital-acquired infections are
two entities associated with increased morbidity and mortality.
They are highly costly and constitute a great burden to the
health care system. Vitamin D deficiency (,20 ng/ml) is
prevalent and may be a key contributor to both acute and
chronic ill health. Vitamin D deficiency is associated with
decreased innate immunity and increased risk for infections.
Vitamin D can positively influence a wide variety of microbial
infections.
Herein we discuss hospital-acquired infections, such as
pneumonia, bacteremias, urinary tract and surgical site infec-
tions, and the potential role vitamin D may play in ameliorat-
ing them. We also discuss how vitamin D might positively
influence these infections and help contain health care costs.
Pending further studies, we think it is prudent to check vitamin
D status at hospital admission and to take immediate steps
to address existing insufficient 25-hydroxyvitamin D levels.
Introduction
There is increasing evidence that vitamin D deficiency plays
an important role in worsening outcomes and increasing the
susceptibility to infections. Vitamin D has potential benefits on
innate immunity and potentiates antimicrobial actions through
a variety of mechanisms. Vitamin D has potential antimicrobial
actions against different organisms, such as bacteria, viruses
and fungi.
It is also well known that hospital acquired infections constitute
a major cause of hospital morbidity and mortality. Viewing the
widespread lack of testing of 25-hydroxyvitamin D [25(OH)D]
levels in the inpatient setting, and the possible beneficial effects of
getting sufficient levels, we raise in this article the potential
association between vitamin D deficiency and the risk of
acquisition of unnecessary infections during a hospital stay.
Burden of Hospital-Acquired Infections
Hospital-acquired infections (HAIs) are a leading cause of death
in the US health care arena, with an overall estimated annual
incidence of 1.7 million cases
1
and 100,000 deaths.
2
As a result,
HAIs have given rise to state laws, legislative proposals at the
federal level, public-private initiatives, and work at the hospital
system and individual hospital level.
2
They constitute a sub-
stantial cause of morbidity and mortality. Pneumonia was the
most likely disease, followed by bacteremias, urinary tract infec-
tions, surgical site infections and others.
3
On the basis of
published medical and economic literature, HAIs in US hospitals
generate an estimated $28.4 billion$45 billion in excess health
care costs annually.
4
Similarly, 12.7% of admitted patients developed HAIs,
doubling the cost of these patientshospital stays. The totals for
159 patients were $1.48$3.34 million in medical costs and
$5.27 million for premature death, and excess length of stay
(LOS) totaled 8441,373 hospital days.
5
Patients with sepsis had
a nearly 6-fold higher odds of death than patients without an
HAI. Patients with other HAIs had a 1.5- to 1.9-fold higher odds
of mortality than control subjects. Patients with HAIs had costs
that were approximately 2- to 2.5-fold higher than those of
patients without HAIs. The median LOS was approximately
2-fold higher in patients with HAIs than in patients without
HAIs.
6
For example, results from a population-based data set
indicated that mortality and LOS are increased among inflam-
matory bowel disease patients who develop HAIs. Most HAIs
were from catheter-associated urinary tract infections (UTIs).
7
HAIs increase morbidity and mortality in intensive-care units
(ICUs) not only for adults (including the elderly) but also for
newborn infants.
8
Multiple challenges stand against the implementation of HAI
reduction plans: poor adherence, insufficient resources, staffing
problems, lack of culture change, no impetus to change, and
issues related to staff and patient education.
9
The rates of hospital-
acquired bacterial infection can be reduced by restricting the
admission of patients colonized with resistant bacteria, increasing
the rate of patient turnover, reducing transmission by infection
control measures and the use of second-line drugs for which
there is no resistance.
10
Many simple measures can decrease
infection rates, such as adequate hand hygiene
11
and, most
recently, vitamin D supplementation.
Antimicrobial Role of Vitamin D
Vitamin D modulates the immune system
12
and appears to have
systemic antimicrobial effects
13
that may be crucial in a variety of
*Correspondence to: Dima A. Youssef; Email: estecina@hotmail.com
Submitted: 12/31/12; Revised: 04/28/12; Accepted: 05/16/12
http://dx.doi.org/10.4161/derm.20789
REVIEW
Dermato-Endocrinology 4:2, 167175; April/May/June 2012; G2012 Landes Bioscience
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both acute and chronic illness. Moreover, vitamin D deficiency
may predispose patients to hypocalcemia, which by itself impairs
normal lymphocyte and neutrophil function.
14
It also decreases
the barrier protective function of cells.
15
Vitamin 1,25-D
3
inhibits
proliferation of T helper 1(Th1) cells [consequently impairing
production of IL-2, tumor necrosis factor aand interferon (IFN)],
as well as T helper 17 (Th17) cells, skewing cytokine production
toward a T helper 2 (Th2) phenotype.
16
Most cells, such as B and
T lymphocytes, monocytes, and dendritic cells, have specific
vitamin D receptors (VDRs).
16
Vitamin D exerts its immuno-
modulatory effects on these cell lines through its effects on the
VDR.
17
Vitamin D tends to favor a mononuclear phenotype,
increasing VDR expression on monocytes and macrophages.
18,19
Vitamin D increases the oxidative burst of macrophages
20
and
facilitates neutrophilic motility and phagocytic function.
21
Vitamin D reduces local and systemic inflammatory responses
as a result of modulating cytokine responses and reducing Toll-
like receptor activation.
22
It directly affects T-cell activation and
the phenotype and function of antigen-presenting cells, especially
dendritic cells.
23
Furthermore, vitamin D stimulates the expres-
sion of potent antimicrobial peptides, such as cathelicidin and
β-defensin 2.
24
Cathelicidins are a family of peptides thought to provide an
innate defensive barrier against a variety of potential microbial
pathogens, such as gram-positive and gram-negative bacteria,
fungi, and mycobacteria, at multiple entry sites, including skin
and mucosal linings of the respiratory and gastrointestinal
systems,
24
as well as viruses.
25
These antimicrobial peptides are
expressed on epithelial surfaces and in neutrophils, are inducible
in keratinocytes in response to infection, and act as natural
antibiotics. In earlier studies, cathelicidins (LL-37 and CRAMP)
were expressed at select epithelial interfaces and may kill bacteria
such as group A Streptococcus.
26,27
Studies in mice showed that
deletion of the cathelicidin gene, Cnlp, results in increased
susceptibility to group A Streptococcus infection. Keratinocytes
inhibit the growth of S. aureus, due partially to their ability to
synthesize and activate cathelicidin.
28
The human cathelicidin,
hCAP18, is a component of the innate immune system and has
broad antimicrobial activity conferred by its C-terminal fragment,
LL-37. hCAP18 is produced in leukocytes and is induced in
barrier organs upon inflammation and infection; hCAP18 also
works in the reepithelialization of skin wounds.
29
To resist innate
immunity, bacteria can develop enzymes that inactivate cathe-
licidins. Thus, streptococcal cysteine protease SpeB-mediated
inactivation of LL-37 is noted in patients with severe group A
Streptococcus tissue infections.
30
However, addition of cathelici-
dins by combining synthetic cathelicidin peptides in vitro, by
producing human keratinocytes that overexpress cathelicidins in
culture, showed increased resistance to infections with group A
Streptococcus.
31
In case of prolonged deficiency of both dietary
vitamin D and calcium, vitamin D deficiency may predispose to
hypocalcemia, which impairs normal lymphocyte and neutrophil
function and potentially increases the risk of acquiring infec-
tious diseases.
32
Vitamin D-deficient patients are susceptible to
increased nosocomial infections, such as pneumonia, sepsis and
central line infections.
16,33
Neutrophils, macrophages, lymphocytes, monocytes and
natural killer cells increase the expression of these antimicrobial
peptides with 25(OH)D stimulation.
34
Human β-defensin 2
(HBD-2) is beneficial in multidrug-resistant microbes in vitro.
35
Human β-defensin 3 (HBD-3) is an antimicrobial peptide that
exhibits broad-spectrum antimicrobial activity against gram-
positive/negative bacteria and fungi.
36
It could be more potent
than HBD-2 in S. aureus skin infections.
37
Moreover, the bacterial
protein flagellin stimulates the mucosal surface innate immunity
by production of antimicrobial peptides and may generate cyto-
protection and control infection in the cornea and other mucosal
tissues.
38
Enhanced antimicrobial peptide production may also
improve skin lesions in psoriasis and atopic dermatitis.
39
Use of Vitamin D in Infectious Diseases
In a previous publication, we outlined the most important actions
of vitamin D against many infections, whether they are bacterial,
mycobacterial, fungal, parasitic, or viral.
40
We also found that
vitamin D deficiency was intimately linked to adverse health
outcomes and costs in veterans with staphylococcal and Clostri-
dium difficile (C. difficile) infections. Vitamin D-deficient patients
with C. difficile or staphylococcal infections had costs more than
five times higher than those of nondeficient patients. The total
length of hospital stay was four times greater in the vitamin D-
deficient group. Also, the total number of hospitalizations was
significantly greater in vitamin D-deficient patients.
41
Similarly,
vitamin D-deficient patients with MRSA and Pseudomonas
aeruginosa infections had higher costs and service utilization than
patients who were not vitamin D deficient.
42
In a retrospective
study by McKinney and colleagues, ICU survivors had a signifi-
cantly lower rate of vitamin D deficiency than did nonsurvivors
(28% vs. 53%). The risk of death was significantly higher in ICU
patients with vitamin D deficiency.
43
Most recently, Higgins et al.
conducted a prospective study to evaluate the burden of vitamin
D deficiency in intensive care unit patients. Serum 25(OH)D was
checked upon admission and at 10 d after admission and the
patients were followed up at 28 d. Twenty-six percent were
deficient and 56% were insufficient. 25(OH)D status was not
significantly associated with 28-d all-cause mortality. However,
higher levels of 25(OH)D were associated with a shorter time-to-
alive ICU discharge. 25(OH)D-deficient patients showed a trend
toward a higher infection rate.
44
Vitamin D therefore appears to
be important for patients with critical illness. On the basis of US
epidemiologic studies, Grant hypothesized that solar UVB light
and vitamin D could reduce the risk of septicemia.
45
Grant also
stated that supplementation with vitamin D to mothers and
infants may reduce the risk of sepsis in premature infants.
46
One
study by Jeng and colleagues in critically ill patients pointed at
the important correlation between 25(OH)D levels, vitamin
D-binding protein, and LL-37 levels. These patients had signifi-
cantly lower plasma 25(OH)D concentrations and LL-37 levels
than did healthy control subjects. Vitamin D-binding protein
levels in plasma were significantly lower in critically ill subjects
with sepsis than in critically ill subjects without sepsis.
47
Therapy
with vitamin D in animal models of sepsis improves blood
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coagulation parameters in disseminated intravascular coagulation
and modulates levels of systemic inflammatory cytokines,
including tumor necrosis factor aand interleukin 6.
48
Vitamin D deficiency is also more prevalent in blacks than in
whites.
49,50
Severe sepsis occurs more often and leads to more
deaths in black than in white individuals. Racial differences in
severe sepsis are explained by both a higher infection rate and a
higher risk of acute organ dysfunction in black than in white
individuals.
51
Currently, prescribing traditional antimicrobials for infectious
processes is customary in medicine. The current use of antimicro-
bials in the United States costs billions of dollars, and the overuse
of antibiotics persists and contributes to the emergence of resistant
organisms.
52
Vitamin D is likely to emerge as a powerful and
hitherto unrecognized antimicrobial agent. Evidence is mounting
that vitamin D could help to manage infectious illnesses. But does
vitamin D deficiency cause infections? This question remains. Hill
proposed one way to determine causality in a biological system,
53
on the basis of nine criteria: strength of association, consistency,
specificity, temporality, biological gradient, plausibility, coher-
ence, experiment and analogy. The more criteria that are elicited,
the better the case for causality. Some examples of applying Hills
criteria include the relationship between vitamin D as a risk-
reduction factor for several types of cancer
54
and that of vitamin D
deficiency and periodontal disease.
55
Below we discuss the most
common HAIs and the beneficial role of vitamin D. Table 1
summarizes the effects of vitamin D on each entity.
Bacteremias and Central Vascular
Catheter-Associated Bloodstream Infections
Patients with health care-associated, community-acquired bac-
teremia have more malignancies, open wounds at admission, and
intravascular catheter-related infections.
56
Most pneumococcal
bloodstream infections (BSIs) are community acquired, although
HAIs are common in neutropenic patients.
57
Critically ill patients
who develop ICU-acquired BSIs suffer excess morbidity and
mortality and incur significantly increased health care costs.
58
According to the latest News and Numbers from the Agency for
Healthcare Research and Quality, septicemia was the single most
expensive condition treated in US hospitals, at nearly $15.4
billion in 2009, including community- and hospital-acquired
cases. The federal agency also found that the number of hospital
stays principally for septicemia more than doubled between 2000
and 2009, making it the sixth most common principal reason
for hospitalization in 2009. Also, the in-hospital death rate for
septicemia was 16% in 2009, more than eight times as high as for
all other hospital stays.
59
Streptococcus pneumoniae is a common cause of community-
acquired pneumonia and bacteremia. White and colleagues
confirmed that the wintertime predominance of invasive
pneumococcal disease in Philadelphia is related to extended
periods of low UV radiation. They suggested that the mechanism
of action of diminished sunlight exposure on disease occurrence
may be due to direct effects on pathogen survival or host immune
function via altered 1,25(OH)
2
D production.
60
In dialysis patients, vitamin D deficiency was among several
pathophysiologic factors that enhance the risk of infections in this
population. Twenty to 30% of dialysis patients develop infection,
and 2030% of these die from their infection. Sepsis and
bacteremia are significantly more frequent, and their mortality is
50 times higher than in the healthy population.
61
In a study by Lee and colleagues, 17% of intensive care unit
patients had undetectable levels of 25-hydroxyvitamin D
[25(OH)D].
32
In a different study, 20% of critically ill patients
with bacterial sepsis had hypocalcemia, and their mortality rate
Table 1. Effects of vitamin D on HAIs
HAI Effect References
Intensive care unit infections Higher levels of 25(OH)D were associated with a shorter time-to-alive
ICU discharge. 25(OH)D-deficient patients had higher infection rate
44
Bacteremia Increased prevalence of pneumococcal sepsis in wintertime 60
Bacteremia, dialysis patients Increased risk of infections, sepsis and bacteremia in deficiency 61
Bacterial sepsis 66% higher mortality rate for low vs. high serum 25(OH)D 62
Community acquired pneumonia Higher 30-d mortality in case of severe deficiency 68
Pneumonia in Children Higher oxygen supplements and ventilator need in deficiency 69, 70
Pneumonia Supplementation with 10002000 IU/d for five daysno effect 74
Pneumonia associated with influenza Case-fatality rate was significantly reduced in regions with higher solar UVB doses 79
Clostridium difficile Vitamin D protects macrophages against death
Deficiency was associated with higher costs
86
41
Catheter-associated urinary
tract infections
VDR ApaI polymorphism seems to be protective. Tt and tt genotypes have higher risk of
UTI.
Vitamin D
3
supplementation increased cathelicidin production in bladders infected with
uropathogenic Escherichia coli.
9092
Surgical site infections 50,000 IU dose eliminated wound infections Donald Miller (Personal
communication)
Virulent organisms such as MRSA S. aureus colonization decreased by 6.6% for each 5-nmol/l increase in 25(OH)D 105
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was significantly higher (50%) than that of normocalcemic
patients with sepsis (29%).
62
Vitamin D deficiency in the obese
may have a role in the pathogenesis of endotoxemia and adipose
inflammation.
63
Health Care-Associated Pneumonia
and Hospital-Acquired Pneumonia
Health care-associated pneumonia (HCAP) usually develops in
patients in outpatient facilities, such as nursing homes, long-term
care facilities, and dialysis centers. HCAP should be dealt with as
if it is hospital-acquired pneumonia (HAP) and should be treated
as such until final cultures are available. Analysis of multi-
institutional clinical data showed that mortality associated with
HCAP is higher than that with community-acquired pneu-
monia.
64
Postoperative HAP is a major risk associated with
surgery. In one study, 10.7% of patients with HAP after intra-
abdominal surgery died before discharge. HAP was independently
associated with a 4.13-fold increase in risk to be discharged to a
skilled nursing facility. The mean length of hospital stay of these
patients was significantly greater than that of intra-abdominal
surgery patients who did not develop HAP. HAP was independ-
ently associated with a 75% mean increase in total hospital
charges.
65
In children younger than 1 y and those with chronic
medical conditions, hospital-acquired febrile respiratory illness is
caused mainly by viruses such as respiratory syncytial virus and is
associated with increased mortality.
66
Vitamin D promotes lung and bone health.
67
Upon evaluat-
ing the associations between mortality and serum 25(OH)D in
patients with community-acquired pneumonia, Leow and
colleagues verified that severe 25(OH)D deficiency was common
and associated with a higher 30-d mortality rate than that of
patients with sufficient 25(OH)D during winter.
68
Similar find-
ings were noted in children with acute lower respiratory infec-
tion. Patients needing more supplementary oxygen and ventilator
management were those with vitamin D deficiency.
69
Also, in a
case-control study in Nigerian children with pneumonia, those
with hypovitaminosis D and hypocalcemia had more complications
and worse outcomes than those without deficiency.
70
Moreover,
rickets was a significant predictor of reduced success in treating
severe pneumonia in Yemen.
71
In ICU-admitted veterans, a longer
stay was significantly linked to lower vitamin D status.
43
Two
recent reviews describe the role of vitamin D and susceptibility to
chronic lung diseases and thus risk for superimposed infections.
72,73
Given the relationship between 25(OH)D levels and com-
munity-acquired pneumonia, we think that the association is
likely to be even stronger for HAIs. However, in one randomized,
double-blind, placebo-controlled trial in India that involved
children admitted for pneumonia, supplementation with oral
vitamin D of 1,0002,000 IU per day for 5 d was not beneficial
in resolving severe pneumonia.
74
The dose and especially the
duration of vitamin D treatment may have been insufficient to
influence outcome. Cannell and colleagues have advocated much
higher short-term doses for acute illness.
75
Influenza was associated with a higher tendency to develop
superimposed bacterial pneumonia, and prevention may avoid the
higher risk of pneumonia, especially in elderly and chronic lung
disease patients. Whether vitamin D should be implemented as
a mandatory vitamin to prevent pandemic influenza is the
question.
76
Juzeniene et al. studied pandemic and nonpandemic
influenzas in Sweden, Norway, the United States, Singapore, and
Japan. The higher exposure to UVB radiation in summer and
consequently higher 25(OH)D levels protect against influenza.
77
Hayes hypothesizes that influenza pandemics are associated with
solar control of 25(OH)D levels in humans, which increase or
decrease with solar cycledependent UV radiation.
78
Studying the
19181919 influenza pandemic, Grant and Giovannucci deter-
mined that vitamin D, by producing antimicrobial peptides and
reducing production of proinflammatory cytokines, decreases the
development of pneumonia after infection with influenza virus.
79
Also one randomized controlled trial involving Japanese school-
children found a relative risk of influenza of 0.36 in those taking
1,200 IU/day compared with those taking 200 IU/day.
80
However, Shaman et al. studied levels of 25(OH)D to see if it
can be used to simulate influenza rates. They found it unlikely
that seasonal variations in vitamin D levels principally determine
the seasonality of influenza in temperate regions.
81
We believe that this finding also applies to patients in the
hospital, especially those infected with the influenza virus, and
the subsequent development of HAP.
Clostridium difficile Infections
Clostridium difficile is the most common cause of nosocomial
infectious diarrhea in the United States. C. difficile-associated
disease (CDAD) can be severe and fatal. C. difficile infection
(CDI) is a major cause of hospital-acquired diarrhea and is most
commonly associated with changes in normal intestinal flora
caused by administration of antibiotics. In Massachusetts,
between 1999 and 2003, CDAD management consumed
55,380 inpatient-days and cost $51.2 million. Based on this
study, a conservative estimate of the annual US cost for CDAD
management was expected to be $3.2 billion.
82
In one institu-
tion, over a 5-y period, the economic burden of CDAD was
increasing to the point that its associated medical expenditures
approached $1 million per year.
83
An analysis by the Centers for
Disease Control and Prevention revealed that, in the United
States, CDI continues to increase, with more than 250,000 US
hospitalizations in 2005 associated with it.
84
Vitamin D has been found to play a protective role in the gut.
Vitamin D and the VDR are required for the development and
function of two regulatory populations of T cells: the iNKT cells
and CD4/CD8aa intraepithelial lymphocytes (IEL). Protective
immune responses that depend on iNKT cells or CD8aa IEL are
therefore impaired in the vitamin D or VDR deficient host and
the mice are more susceptible to immune-mediated diseases in
the gut.
85
Also, vitamin D protects macrophages against death
induced by Cdif toxin (TcdA/B)-induced intestinal injury.
86
In
one study undertaken in Weill Cornell College of Medicine and
New York Hospital Queens, 30 d clearance rates were 53% in
those with normal serum levels of 25(OH)D vs. 26% in those
with levels below 21 ng/dL. Mortality rates were also higher in the
170 Dermato-Endocrinology Volume 4 Issue 2
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patients with low vitamin D, at 56% compared with 33% for
those with serum 25(OH)D levels of 21 ng/dL or above.
87
We
discussed previously the health care costs of patients with CDI
associated with vitamin D deficiency. In the outpatient setting,
vitamin D deficiency in patients with C. difficile and staphylo-
coccal infections were associated with significantly increased total
outpatient costs and fee-based consultation.
In addition the total number of hospitalizations was also
significantly greater in the vitamin D-deficient group. In the
inpatient setting, vitamin D-deficient patients had higher labora-
tory, pharmacy, and radiology costs. These deficient patients
had five times higher costs than the non-deficient patients,
manifested by four times greater length of hospital stay and more
hospitalizations.
41
Catheter-Associated Urinary Tract Infections
Almost 60% of patients having a foley catheter in the hospital do
not need it. Twenty-six percent of patients using indwelling
catheters for 210 d get bacteriuria. Among those, symptoms of
urinary tract infections (UTIs) develop in an estimated 24%, and
bacteremia in 3.6%. Each episode of UTI is expected to cost an
additional $676, and catheter-related bacteremia at least $2,836.
88
Changes in reimbursement policies have focused attention on
the use of indwelling catheters in the critical care unit as well as
their role in hospital-acquired UTIs. Implementation of an
evidence-based prevention program can significantly reduce both
the prevalence of indwelling catheterization and the incidence
of hospital-acquired, catheter-associated UTIs.
89
One review
discussed the role of vitamin D in the prevention of infections,
including UTIs.
90
A study evaluated the different vitamin D
receptor polymorphisms in children with UTIs and those with a
history of UTI. The ApaI polymorphism was significantly
increased in the control group and considered a protective factor.
Comparing with the TaqI, the study found that both the Tt and
tt genotypes carried minimal increased risk of UTI.
91
To prove the
activity of vitamin D in protecting against UTIs, Hertting and
colleagues demonstrated a significant increase in the production of
cathelicidin after vitamin D
3
supplementation in bladders infected
with uropathogenic Escherichia coli. The authors recommended
that vitamin D be considered as a potential preventive measure
for UTIs.
92
Surgical Site Infections
The first report of a group A Streptococcus hospital outbreak was
reported in an acute care facility in Texas. The wound care team
was the means of transmission: a member of this team was
colonized with the matching type.
93
Surgical site infections caused
by methicillin-resistant Staphylococcus aureus (MRSA) are increas-
ing significantly and are independently associated with higher
mortality, increased length of stay and higher cost.
94
In a personal communication with Seattle cardiothoracic
surgeon Donald Miller M.D., he indicated that the post-
pericardiotomy syndrome occurring in veterans after coronary
artery bypass surgery virtually disappeared, as did sternotomy
wound infections, after a preoperative dose of 50,000 IU of
cholecalciferol.
Vitamin D enhances antimicrobial peptide production in the
skin. Deficiency in antimicrobial peptide production contributes
to the increased susceptibility of S. aureus skin infections in
patients with atopic dermatitis.
95
Antimicrobial peptides may
contribute to host defense through wound repair
96
and clearance
of bacteria at various barrier sites.
97
Applying topical vitamin D
would result in faster recovery from many skin disorders, both
infectious and noninfectious, including wounds, bacterial and
viral infections, diabetic ulcers, and chronic skin ulcers. Arnold
and van de Kerkhof investigated the efficacy of MC903, a vitamin
D
3
analog, in reducing hyperproliferation as determined by
levels of ornithine decarboxylase in 15 patients with chronic
plaque psoriasis. Eight of 11 patients treated with MC903
showed clinical improvement.
98
Several other studies showed beneficial outcomes in skin
and soft tissue in the presence of vitamin D. For example, one
study compared outcomes of periodontal surgery and teriparatide
administration in vitamin D-sufficient and vitamin D-insufficient
individuals. Placebo patients with baseline vitamin D deficiency
had significantly less clinical attachment and probing depth
reduction than vitamin D-sufficient individuals. At 1 y, infrabony
defect resolution was greater in teriparatide-treated vitamin D-
sufficient individuals.
99
In an animal study, incidence of injection
site lesions was lowest among animals given vitamin AD
3
, a water
emulsifiable solution to be used as a supplemental source of
Vitamins A and D
3
in cattle (as calves, at both branding and
weaning times) and was highest in cattle given injections of 5 mL
of clostridial products at branding or of long-acting oxytetracy-
cline antibiotic at weaning.
100
Infections due to Virulent Organisms, such as MRSA
In one hospital, most MRSA infections were health care asso-
ciated: 58.4% were community-onset infections, 26.6% were
hospital-onset infections, and 13.7% were community-associated
infections, and the rest could not be classified. The incidence
rates were highest among persons aged 65 y and older, blacks,
and males.
101
Hospital-acquired MRSA and community-acquired
MRSA are important causes of pneumonia and present diagnostic
and therapeutic challenges.
102
Nasal colonization with S. aureus is a significant risk factor
for ICU-acquired S. aureus infections, and strategies to control
these infections should target both MSSA (methicillin-susceptible
S. aureus) and MRSA colonization.
103
A secondary data analysis of
the National Health and Nutrition Examination Survey, 2001
2004, showed that vitamin D deficiency was associated with
an increased risk of MRSA nasal carriage.
104
To support this
finding, the Tromsø Staph and Skin Study 20072008 demon-
strated that in nonsmoking men, the probability of S. aureus
colonization and carriage, respectively, decreased by 6.6% and
6.7% for each 5-nmol/L increase in serum 25(OH)D concentra-
tion. This study also established serum 25(OH)D thresholds of
greater than 59 nmol/L and at least 75 nmol/L for ~30% and
~50% reduction in S. aureus colonization and carriage,
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respectively.
105
Vitamin D supplementation to reach a serum 25
(OH)D above 75 nmol/L may reduce the incidence of MSSA and
MRSA infection and thus may be a significant synergistic step in
preventing HAIs.
Appropriate Dose of Vitamin D
Vitamin D deficiency is associated with increased mortality
rates.
106
A meta-analysis of 11 prospective studies of serum
25(OH)D at time of enrollment found a significantly reduced
mortality rate for those with serum 25(OH)D concentrations of
75 nmol/L compared with those with less than 42 nmol/L.
107
Another recent paper estimated that doubling worldwide popula-
tion mean serum 25(OH)D concentrations, from 5055 nmol/L
to 100105 nmol/L, would reduce mortality rates by 717% and
increase life expectancy by 2 y.
108
Also, a recent publication of a
meta-analysis of 12 prospective studies showed that a 20nmol/l
increase in 25(OH)D levels was associated with an 8% lower
mortality in the general elderly population.
109
The optimal serum 25(OH)D concentration for bacterial and
viral immunity is still a controversial matter. The 2011 report on
dietary reference intakes for calcium and vitamin D from the
Institute of Medicine gives guidelines for the daily vitamin D
needed supplementation, based on a review of randomized
controlled trials that they deemed of high quality, finding strong
evidence only for beneficial effects for bones.
110
They recom-
mended a daily dose of 600 IU of vitamin D. They also
considered a serum level of 16 ng/mL to meet the needs for
almost half the population. This report suggested that vitamin D
deficiency is overdiagnosed. However, a 600-IU daily dose is
inadequate to achieve the health-related goals we have
described.
111
And because the response to vitamin D supple-
mentation varies among patients, many patients need higher
doses.
112
Norman and colleagues
113
addressed the current public
health needs of vitamin D. Recently, the Endocrine Society
released Evaluation, Treatment, and Prevention of Vitamin D
Deficiency: An Endocrine Society Clinical Practice Guideline, which
recommended doses of vitamin D supplementation for each age
group. Adults require at least 1,5002,000 IU of vitamin D
per day to maintain a blood level of 25(OH)D above 75 nmol/L.
This dosage is similar to the requirements for those aged 5070 y
and for pregnant women.
110
Moreover, results in the literature
on severe respiratory infections support these findings. In an
observational study, individuals with serum 25(OH)D concentra-
tions greater than 95 nmol/L had low rates of acute viral res-
piratory tract infections, whereas those with lower concentrations
had a 50% chance of developing such infections during a half-year
observational period. In a 2009 Paris meeting, a panel of vitamin
D researchers endorsed a serum 25(OH)D concentration of 75
100 nmol/L.
115
Sabetta et al. demonstrated that maintenance of a
vitamin D serum concentration of 38 ng/mL or higher should
significantly reduce the incidence of acute viral respiratory tract
infections, including influenza, at least during the fall and winter
in temperate zones.
116
Conclusion
For HAIs, pointing to vitamin D deficiency as the sole risk factor
is difficult. Patients admitted to the hospital are sicker and thus
are more prone to acquire pathogens and manifest illnesses.
However, vitamin D deficiency can increase this probability by
decreasing the host innate defense mechanisms. We have
suggested the use of vitamin D in the management of acute
illness in elderly patients and those with an underlying chronic
illness.
117
This review aims to show the potential benefits of
vitamin D in infection. Given the prevalence of vitamin D
deficiency, we believe that intensive vitamin D supplementation
in patients before and during hospital stays could improve health
outcomes. Vitamin D is inexpensive, and adequate supplementa-
tion can be achieved at minimal cost. Vitamin D use could reduce
inappropriate antibiotic prescription and boost therapeutic res-
ponse when combined with appropriate antibiotic use. Although
prospective double-blind studies are needed to confirm the
antimicrobial effects of vitamin D, the existing evidence for an
antimicrobial effect by vitamin D is compelling. We recommend
that vitamin D deficiency be taken into greater consideration as a
risk factor for immunodeficiency and increased susceptibility to
infections. To note that most recently, Cannell announced that it
has become possible to prescribe vitamin D
3
, as 50,000 IU once
weekly, and it can also be prescribed as once every 2 weeks.
118
Disclosure of Potential Conflict of Interest
W.B.G. receives or has received funding from the UV Founda-
tion (McLean, VA), Bio-Tech-Pharmacal (Fayetteville, AR), the
Vitamin D Council (San Luis Obispo, CA), and the Vitamin D
Society (Canada).
Acknowledgments
This material is the result of works supported with resources and
the use of facilities at the Mountain Home VAMC. The contents
of this report do not reflect the position of the US government
and the Department of Veterans Affairs.
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www.landesbioscience.com Dermato-Endocrinology 175
... At the same time, the systematic review by Charan et al. [36] indicated that it may be even more observable in children than in adults. Some similar observations were formulated for hospital-acquired infections, including inter alia wound infections and sepsis [37], but vitamin D failed to be effective against respiratory infections after lung transplants [38]. During the COVID-19 pandemic, numerous studies also verified the effectiveness of vitamin D in the prevention and treatment of COVID-19 infection. ...
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Vitamin D is indicated to be beneficial for the prevention and treatment of both respiratory health and mental health problems, while mental health issues are a common consequence of diseases of the respiratory system. The aim of the presented systematic review was to gather available evidence regarding the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases obtained within randomized controlled trials (RCTs). The systematic review was conducted on the basis of the PubMed and Web of Science databases in agreement with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), while being registered within the database of the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020155779). A total of 8514 studies published before September 2021 were screened and 5 RCTs were included, which were assessed using the revised Cochrane risk-of-bias tool for randomized trials. Screening, inclusion, reporting, and assessment were conducted by two researchers independently. The studies focused on the assessment of patients with chronic obstructive pulmonary disease, but also increased susceptibility to respiratory tract infections, pulmonary tuberculosis, and bronchial asthma. The studies were conducted for various periods of time—from 2 months to a year—while the dose of vitamin D applied was also diverse—from 4000 IU applied daily, to 100,000 IU applied weekly, or monthly. The psychological measures applied within the studies allowed the assessment, mainly, of quality of life, but also well-being, and depression. For the majority of studies, some concerns regarding risk of bias were defined, resulting from the randomization process and selection of reported results; however, for one study, the risk was even defined as high. Within the included studies, three studies confirmed a beneficial effect of vitamin D (including those with a high risk of bias), but two studies did not confirm it. Taking into account the evidence gathered, in spite of a positive influence of vitamin D on mental health in individuals with increased susceptibility to respiratory tract infections and bronchial asthma, the conducted systematic review is not a strong confirmation of the beneficial effect of the supplementation of vitamin D on mental health in adults with respiratory system diseases.
... 11,12 Vitamin D deficiency is related to chronic diseases, the tendency of some infections, and worsening of infections. 13 Treating vitamin D deficiency is cheap and may improve some clinical outcomes of chronic diseases and infections. Diagnosis and treatment of vitamin D deficiency and toxicity depend on laboratory measurements of 25(OH)D levels. ...
... Некоторые авторы рассматривают возможность применения витамина D для компенсации его дефицита в качестве профилактики COVID-19, улучшения прогноза и снижения риска летальности [53,54]. Безопасной дозой этого витамина является суточная доза колекальциферола, не превышающая 10 000 МЕ [55], однако обсуждается применение более высоких доз, достигающих 50 000 МЕ холекальциферола для снижения риска COVID-19 [56]. ...
Article
The new coronavirus infection (COVID-19) is associated with a wide spectrum of various clinical manifestations including involvement of the musculoskeletal system which can persist for a long time after the infection. Supposedly, pathogenesis of musculoskeletal manifestations of COVID-19 is primarily caused by systemic inflammation accompanied by cytokine hyperexpression (interferon γ, interleukins 1β, 6, 8, 17, tumor necrosis factor α), as well as hypoxia leading to overproduction of inflammatory cytokines, activation of bone reabsorption by osteoclasts and subsequent decrease of mineral bone density and osteonecrosis in some cases. Additionally, some drugs prescribed to patients with COVID-19 (some antiviral drugs and glucocorticoids) should also be taken into account as they can lead to development of musculoskeletal pathology. In the acute period of COVID-19, myalgias are common, but in rare cases myositis with proximal muscular weakness and increased levels of creatine phosphokinase, lactate dehydrogenase can occur. Arthralgias in the acute period of COVID-19 are rarer than myalgias. In the studies of clinical manifestation of COVID-19, frequency of arthralgias and myalgias in the acute period is between 15.5 and 50 %. After COVID-19, frequency of arthralgias and myalgias gradually decreases, however there are cases of long-term joint and muscle pains, as well as post-viral arthritis, development of arthritis in the context of various autoimmune disorders. Myalgias and arthralgias during COVID-19 usually regress spontaneously and in most patients do not require prescription of antipain medications, but in some cases pain management is necessary. Use of non-steroid anti-inflammatory drugs and vitamin D during COVID-19 is a safe and effective method of pain management, including myalgia and arthralgia. Rehabilitation programs play an important role in improvement of functional state and patient recovery after moderate and severe COVID-19.
... Data supportive of the theory that deficiency leads to infections largely rest on the fact that seasonal influenza infections generally peak in conjunction with times of the year when 25(OH)D concentrations are lowest [205]. Further, the onset of the epidemic and higher case load in countries during the winter season also raises the possible association with low vitamin D status [206]. Rhodes et al first identified this link by comparing the mortality of COVID-19 in relation to country latitude and found that, even after adjusting for age, there was a 4.4% increase in mortality for each degree latitude north of 28°. ...
Article
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In December 2019, coronavirus disease 2019 (COVID-19), a severe respiratory illness caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The greatest impact that COVID-19 had was on intensive care units (ICUs), given that approximately 20% of hospitalized cases developed acute respiratory failure (ARF) requiring ICU admission. Based on the assumption that COVID-19 represented a viral pneumonia and no anti-coronaviral therapy existed, nearly all national and international health care societies recommended "supportive care only" avoiding other therapies outside of randomized controlled trials, with a specific prohibition against the use of corticosteroids in treatment. However, early studies of COVID-19-associated ARF reported inexplicably high mortality rates, with frequent prolonged durations of mechanical ventilation (MV), even from centers expert in such supportive care strategies. These reports led the authors to form a clinical expert panel called the Front-Line COVID-19 Critical Care Alliance (www.flccc.net). The panel collaboratively reviewed the emerging clinical, radiographic, and pathological reports of COVID-19 while initiating multiple discussions among a wide clinical network of front-line clinical ICU experts from initial outbreak areas in China, Italy, and New York. Based on the shared early impressions of "what was working and what wasn't working", the increasing medical journal publications and the rapidly accumulating personal clinical experiences with COVID-19 patients, a treatment protocol was created for the hospitalized patients based on the core therapies of methylprednisolone, ascorbic acid, thiamine, heparin and non-antiviral co-interventions (MATH+). This manuscript reviews the scientific and clinical rationale behind MATH+ based on published in-vitro, pre-clinical, and clinical data in support of each medicine, with a special emphasis of studies supporting their use in the treatment of patients with viral syndromes and COVID-19 specifically.
... According to World Health Organization (WHO) criteria, the severity of COVID-19 patients was classified into 1-10. After that, patients were grouped into three according to the WHO clinical progression scale; (1) mild ambulatory disease (1-3), (2) hospitalized: moderate disease (4-5), (3) hospitalized: severe disease and dead (6)(7)(8)(9)(10). 20 The patients' requirement for noninvasive mechanical ventilation (NIMV) or reservoir mask, their requirement for admission to intensive care unit (ICU), mortality, and WHO clinical progression scales were also reviewed. ...
Article
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Purpose Vitamin D deficiency has emerged as another potential risk factor for coronavirus disease (COVID-19) due to the immunomodulatory effects of 25 hydroxyvitamin D [25 (OH)D]. Vitamin D receptor (VDR) gene polymorphisms such as Fok I, Bsm I, Apa I, and Taq I are also associated with different courses of viral infections. This study aimed to evaluate the association between the VDR gene polymorphism at Fok I, Taq I, Bsm I, and Apa I genotypes and the prognosis of COVID-19 in respect to vitamin D deficiency. Methods Two-hundred ninety-seven patients with COVID-19 were enrolled. Serum 25 (OH)D levels were measured. Four variant regions of the VDR gene, FokI, BsmI, ApaI, and TaqI were determined. Results Eighty-three percent of subjects had vitamin D deficiency, and 40.7% of the whole group had severe deficiency. Median 25 (OH)D level was 11.97 ng/mL. Vitamin D levels were not related to inflammatory markers, disease severity, admission to intensive care unit (ICU), and mortality. While disease severity was related to Fok I Ff genotype, it was Taq TT genotype for ICU admission. Moreover, the ApaI aa genotype was common among the patients who were died. None of the deceased subjects had the Fok I FF genotype. Conclusion 25 (OH)D levels were not related to the severity and mortality of COVID-19. VDR gene polymorphisms are independently associated with the severity of COVID-19 and the survival of patients. This article is protected by copyright. All rights reserved.
... In recent years, an increasing number of studies have investigated the effect of 25-OH vitamin D on progression-free survival and overall survival in patients with colorectal cancer [26][27][28]. It has also been revealed that infectious complications are increased in hospitalized patients with vitamin D deficiency because of its decreased immunomodulatory effects [29,30]. The effects of vitamin D on the immune system are mainly based on the presence of vitamin D receptors on B and T lymphocytes and macrophages, and promoting chemotaxis, autophagy, and phagolysosomal function in innate immune cells. ...
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Determining the modifiable risk factors for postoperative complications is particularly significant in patients undergoing colorectal surgery since those are associated with worse long-term outcomes. Consecutive newly diagnosed 104 colorectal cancer patients were prospectively included in this single-center observational study. Preoperative serum 25-OH vitamin D levels were measured and analyzed for infectious and postoperative complications. Serum 25-OH vitamin D levels were found to be < 20 ng/ml in 74 patients (71.2%) and ≥ 20 ng/ml in 30 patients (28.8%); and the mean serum 25-OH vitamin D level was 15.95 (± 9.08) ng/ml. In patients with surgical site infection and infectious complications, 25-OH vitamin D levels were significantly lower than patients without complications (p= 0.036 and p = 0.026). However, no significant difference was demonstrated in 25-OH vitamin D levels according to overall postoperative complications. Our results suggest that vitamin D levels might be a potential risk factor for infectious complications in patients undergoing colorectal cancer surgery.
... Escherichia coli infection is the most common pathogen (80% to 90%) causing the UTI. 9 Vitamin-D Supplementation before and during the episode of urinary tract infection can improve the clinical status. 10 Vitamin-D Supplements are available in market at reasonable price. UTI can be managed more appropriately by using both vitamin-D supplements and antibiotics. ...
Article
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Objective: To determine Vitamin-D status in children with urinary tract infection. Methods: A Cross-sectional study was done at Pediatric Department, Liaquat University Hospital Hyderabad, from July 2019 to March 2020. A total of 172 children of either gender from 2 to 60 months of age with confirmed urinary tract infection (UTI) (having positive urine C/S report) were included in the study. The child who received antibiotics 48 hours prior or already on immunosuppressive drugs and steroids from previous health record or by taking clinically relevant history), children with CKD on vitamin-D supplementation, and known case of Vitamin-D deficiency were also excluded from the study. All study participants were evaluated for vitamin-D level by high performance liquid chromatography. Urine sample was collected for C/S and 1 cc venous blood was taken for Vitamin D status (ng/ml). The mean ± standard deviation (SD) and stratification was calculated for age, duration of urinary tract infection and vitamin-D level. Post stratification chi-square test was applied for all categorical variables at 95% confidence interval (CI) and P-value ≤0.05 was considered significant. Results: The average age of the patients was 41.51±18.34 months. There were 130 (75.58%) females and 40 (23.25%) males. Most common complaint of the children was fever 150 (87.21%). Vomiting was present in 31 (18.02%), abdominal pain 22 (12.79%) and dysuria in 15 (8.72%) children. A total of 129 (75%) children had pyelonephritis and 15 (25%) had cystitis. (Frequency of vitamin-D deficiency in children with diagnosed UTI was 45.93% (79/172). Mild vitamin D deficiency was present in 42 (53.16%) children, while moderate deficiency in 55 (69.62%) children. E. Coli was the most common pathogen in both mild and moderate vitamin D deficiency i.e., 20 (47.61) and 31 (56.36%) respectively. Conclusion: The frequency of urinary tract infection is more common in children having vitamin D deficiency.
Article
To set up the recognition of diet-D in kids with infection of urinary tract. A bypass-sectional research modified into directed on the department of Pediatrics, Carter university sanatorium,IHyderabad, fromIJuly 2019Ito MarchI2020. A sum of 172 young guys and younger girls somewhere in the variety of 2 and 60 months vintage enough have been decided to have urinary lot contamination (UTI) (powerful pee check). C/S record) grow to be remembered for the studies. In view of past well being information or clinically essential medical records, kids who had ate up immunosuppressive medicines and steroids 48 hours previous or had taken nutrient D improvements with CKD, and recognized instances of nutrient D inadequacy were likewise prohibited from the research. All exam members surveyed their nutrient D degrees by way of elite fluid chromatography. Collect pee tests forIC/S and 1Icc of venousIblood for nutrient D recognition (ng/ml). Decide the advise ± desired deviationI(SD) andIdefinition antiqueIsufficient, time period of urinary parcel sickness, and nutrient D diploma. The chi-square test after definition is carried out to all absolute factors with 95% truth stretch (CI), and a P esteem ≤0.05 is considered huge. The recurrence of urinary lot illnesses is greater everyday in children who're nutrient D insufficient.
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The COVID-19 pandemic has caused serious concerns for people around the world. The COVID-19 is associated with respiratory failure, generation of reactive oxygen species (ROS), and the lack of antioxidants among patients. Specified ROS levels have an essential role as an adjuster of immunological responses and virus cleaners, but excessive ROS will oxidize membrane lipids and cellular proteins and quickly destroy virus-infected cells. It can also adversely damage normal cells in the lungs and even the heart, resulting in multiple organ failures. Given the above, a highly potent antioxidant therapy can be offered to reduce cardiac loss due to COVID-19. In modern medicine, nanoparticles containing antioxidants can be used as a high-performance therapy in reducing oxidative stress in the prevention and treatment of infectious diseases. This can provide a free and interactive tool to determine whether antioxidants and nanoantioxidants can be administered for COVID-19. More research and studies are needed to investigate and make definitive opinions about their medicinal uses.
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Vitamin D insufficiency is increasingly recognized as an important risk factor in the pathogenesis of falls and fractures and may increase the risk of other diseases. The aim of this study was to obtain information about the vitamin D supply from a representative cohort of the German population. 264 General practitioners participated in the DeViD-Trial (D-Vitamin in Deutschland) by taking blood samples from their consenting daily ambulant patients regardless of the actual reason for consultation. In these blood samples vitamin D [25(OH)D] and other related parameters were measured at a central laboratory. The patients filled in a simple questionnaire (i.e., age, sex, etc.). The trial was performed between February 26 and May 25, 2007. Laboratory and personal data were documented for 1,343 individuals (615 men, 728 women). The age distribution ranged from 20 to 99 y, the mean age of the whole cohort was 57.6 y (men 58.2, women 57.2). The mean 25-OH-D-value for the whole cohort was 16.2 ng/ml (range: 6.0 to 66.8, median 14.1 ng/ml). Ten percent of the patients had 25(OH)D-values below 7 ng/ml, 65% below 20 ng/ml and 92% showed values below 30 ng/ml. In the more recent literature, 25(OH)D values below 30 ng/ml are regarded as sub-optimal for bone, muscle and general health. Correspondingly it can be stated that in this representative population there is a high prevalence of moderate to severe vitamin D-insufficiency regardless of young or old age.
Article
objective. The purpose of this study was to provide a national estimate of the number of healthcare-associated infections (HAI) and deaths in United States hospitals. Methods. No single source of nationally representative data on HAIs is currently available. The authors used a multi-step approach and three data sources. The main source of data was the National Nosocomial Infections Surveillance (NNIS) system, data from 1990-2002, conducted by the Centers for Disease Control and Prevention. Data from the National Hospital Discharge Survey (for 2002) and the American Hospital Association Survey (for 2000) were used to supplement NNIS data. The percentage of patients with an HAI whose death was determined to be caused or associated with the HAI from NNIS data was used to estimate the number of deaths. Results. In 2002, the estimated number of HAIs in U.S. hospitals, adjusted to include federal facilities, was approximately 1.7 million: 33,269 HAIs among newborns in high-risk nurseries, 19,059 among newborns in well-baby nurseries, 417,946 among adults and children in ICUs, and 1,266,851 among adults and children outside of ICUs. The estimated deaths associated with HAIs in U.S. hospitals were 98,987: of these, 35,967 were for pneumonia, 30,665 for bloodstream infections, 13,088 for urinary tract infections, 8,205 for surgical site infections, and 11,062 for infections of other sites. Conclusion. HAIs in hospitals are a significant cause of morbidity and mortality in the United States. The method described for estimating the number of HAIs makes the best use of existing data at the national level.
Article
In the current era of multidrug-resistant organisms, the clinical spectrum of Streptococcus pneumoniae infection remains unclear, especially in immunosuppressed patients with cancer. We sought to define the characteristics of pneumococcal bacteremia in patients who were receiving care at a comprehensive cancer center. All consecutive episodes of S. pneumoniae bacteremia between January 1998 and December 2002 were evaluated retrospectively. One hundred thirty-five episodes of pneumococcal bacteremia occurred in 122 patients. Sixty-three (52%) of 122 patients had hematologic malignancies; the others had solid tumors. The median Acute Physiology and Chronic Health Evaluation II score was 14 ± 5. Twenty-four episodes (18%) occurred during neutropenia (<500 cells/μL). Sixty-five patients (53%) were receiving antineoplastic therapy, and 36 (30%) were receiving systemic corticosteroids. Twelve (41%) of 29 hematopoietic stem cell transplant (HSCT) recipients had received transplantation within 12 months of the infection diagnosis; 11 patients had graft-versus-host disease (chronic in 10). In 27 episodes (22%), S. pneumoniae bacteremia was considered as a breakthrough infection. Nine (56%) of 16 hospital-acquired episodes of S. pneumoniae bloodstream infection occurred in patients with profound neutropenia, whereas 15 (13%) of 119 episodes of community-acquired infection occurred during neutropenia (p < 0.0002). In 91 episodes (67%), patients had radiographic evidence of pneumonia. Infected catheters were associated with 21 episodes (16%). Forty-eight (36%) of 135 isolates were not susceptible to penicillin (minimum inhibitory concentration [MIC] ≥2 μg/mL); 9 (7%) showed intermediate susceptibility to ceftriaxone (MIC >0.5 and <2.0 μg/mL). Nineteen patients (16%) died within 2 weeks of diagnosis; 18 deaths were attributed to systemic pneumococcal infection. Univariate analysis showed no significant increase in the risk of short-term death in patients with infection due to penicillin non-susceptible organisms (OR [odds ratio], 1.47; 95% confidence intervals [CI], 0.53-4.05; p < 0.46), initially discordant treatment (OR, 1.0; 95% CI, 0.62-665.4; p < 0.16), presence of pneumonia (OR, 1.19; 95% CI, 0.39-3.62; p < 0.76), neutropenia (OR, 1.0; 95% CI, 0.28-4.09; p < 0.92), systemic corticosteroid use (OR, 1.96; 95% CI, 0.69-5.60; p < 0.21), or antineoplastic therapy (OR, 1.45; 95% CI, 1.52-4.05; p < 0.47). Similarly, patients with hematologic cancers compared to those with solid cancers (OR, 1.0; 95% CI, 0.49-3.70; p < 0.56) and recipients of HSCT compared to those with no history of transplantation (OR, 1.0; 95% CI 0.59-12.71; p < 0.20) did not have a less favorable outcome. In conclusion, most pneumococcal bloodstream infections were community acquired, although hospital-acquired infections were common in neutropenic patients. It is noteworthy that initially discordant therapy, penicillin non-susceptible S. pneumoniae, and other conventional predictors of unfavorable outcome were not associated with increased mortality rates in these high-risk patients with cancer. Abbreviations: HIV = human immunodeficiency virus, HSCT = hematopoietic stem cell transplant, MIC = minimum inhibitory concentration.
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Hypocalcemia is a common problem in critically ill surgical patients. We prospectively evaluated whether measurement of the total serum calcium (Ca) concentration or calculation of the serum ionized Ca level (by the McLean-Hastings nomogram) accurately reflects the measured serum ionized Ca level. Although 71% and 58% of 156 predominantly surgical intensive care unit (ICU) patients were hypocalcemic by the total serum Ca or calculated ionized Ca level, respectively, only 12% were hypocalcemic by directly measured serum ionized Ca measurement. The total serum Ca and calculated ionized Ca concentrations were sensitive (95% and 89%, respectively) but lacked specificity (32% and 46%, respectively) in predicting ionized hypocalcemia. Analyses of Ca binding to albumin in the serum of surgical ICU patients and normal subjects suggested that there is a circulating factor in critically ill patients that increases the binding of Ca to albumin. These observations may explain why the McLean-Hastings nomogram underestimates the protein-induced changes in serum Ca in critically ill surgical subjects. We conclude that: total serum Ca and calculated ionized Ca concentrations are poor indicators of the true serum ionized Ca status in critically ill surgical patients, and we recommend direct measurement of serum ionized Ca levels in these patients; and variability in the affinity of Ca for binding proteins in critical illness may explain the poor correlation between serum total and ionized Ca measurements.
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Summary In in vitro studies vitamin D3 proved inhibitory on strains ofStaphylococcus aureus, Streptococcus pyogenes, Klebsiella pneumoniae, Escherichia coli, andCandida albicans. In the presence of 5×104–9×104 IU/ml vitamin D3 the organisms were killed or reacted with a marked growth inhibition.
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Cathelicidins are a family of peptides thought to provide an innate defensive barrier against a variety of potential microbial pathogens. The human and mouse cathelicidins (LL-37 and CRAMP, respectively) are expressed at select epithelial interfaces where they have been proposed to kill a number of gram-negative and gram-positive bacteria. To determine if these peptides play a part in the protection of skin against wound infections, the anti-microbial activity of LL-37 and CRAMP was determined against the common wound pathogen group A Streptococcus, and their expression was examined after cutaneous injury. We observed a large increase in the expression of cathelicidins in human and murine skin after sterile incision, or in mouse following infection by group A Streptococcus. The appearance of cathelicidins in skin was due to both synthesis within epidermal keratinocytes and deposition from granulocyctes that migrate to the site of injury. Synthesis and deposition in the wound was accompanied by processing from the inactive prostorage form to the mature C-terminal peptide. Analysis of anti-microbial activity of this C-terminal peptide against group A Streptococcus revealed that both LL-37 and CRAMP potently inhibited bacterial growth. Action against group A Streptococcus occurred in conditions that typically abolish the activity of anti-microbial peptides against other organisms. Thus, cathelicidins are well suited to provide defense against infections due to group A Streptococcus, and represent an important element of cutaneous innate immunity.