Memo 8 – Maggie Cullather
Atrial Fibrillation is an Independent Risk Factor for Hospital Acquired Pneumonia
This particular study took a look at the association between pre-existing cardiovascular – and more
specifically atrial fibrillation – and hospital acquired pneumonia. Hospital acquired pneumonia is
classified as a primary pneumonia that arises approximately 48 hours after admission into hospitals. It is
currently one of the leading hospital derived infections worldwide which accounts for 13–18% of all
hospital acquired infections that affect 0.5–2.0% of hospitalized patients. Hospital acquired pneumonia
is also associated with elevated morbidity and mortality and increased hospital costs. Atrial fibrillation,
which is the one of the most common forms of arrhythmia in humans, can also cause a multitude of
clinical complications including high blood pressure, coronary heart disease, myocardiopathy, and heart
failure. The researchers in this study pulled data from 8657 admitted patients at the First Affiliated
Hospital of Shantou University Medical College. 1,059 patients had atrial fibrillation and 7,598 did not.
Final results showed that among the atrial fibrillation patients, 274 had hospital acquired pneumonia approximately 25.64% - which was significantly higher than the 276 non-atrial fibrillation patients who
had hospital acquired pneumonia, approximately 3.66%; P<0.001 making the result statistically
insignificant. This increased risk was also associated with high blood pressure, heart failure and age, but
not with gender, smoking, coronary heart disease, diabetes, or congenital heart disease.
References
1. Ji R, Wang D, Shen H, Pan Y, Liu G, Sawanyawisuth K. (2013) Interrelationship among common
medical complications after acute stroke: pneumonia plays an important role. Stroke 44: 3436–
3444. doi:10.1161/STROKEAHA.113.001931 PMID: 24178914
a. Investigation on the association of common in-hospital medical complications after
acute ischemic stroke (AIS) and spontaneous intracerebral hemorrhage (ICH) by
studying patients enrolled in the China National Stroke Registry from 2007 to 2008.
2. American Thoracic Society, Infectious Diseases Society of American. (2005) Guidelines for the
management of adults with hospital-acquired, ventilator-associated, and healthcare-associated
pneumonia. Am J Respir Crit Care Med 171: 388–416. PMID: 15699079
a. This document focuses on the epidemiology and pathogenesis of bacterial pneumonia in
adults emphasizing modifiable risk factors for infection. In addition, the microbiology of
hospital acquired pneumonia is reviewed, with an emphasis on multidrug-resistant
(MDR) bacterial pathogens, such as Pseudomonas aeruginosa, Acinetobacter species,
and methicillin-resistant Staphylococcus aureus.
3. McEachern R, Campbell GD Jr (1998) Hospital-acquired pneumonia: epidemiology, etiology, and
treatment. Infect Dis Clin North Am 12: 761–779, x. PMID: 9779389
a. HAP defined as the development of pneumonia at least 48 hours after hospitalization
and not incubating at the time of admission, is not considered a reportable disease. HAP
is estimated to occur at a rate of 5 to 10 cases per 1, 000 hospital admissions, and
accounting for approximately 13% to 18% of all nosocomial infections, or approximately
300,000 cases annually.
4. Ucgun I, Dagli CE, Kiremitci A, Yildirim H, Ak G, Aslan S. (2013) Effects of isolation rooms on the
prevalence of hospital acquired pneumonia in a respiratory ICU. Eur Rev Med Pharmacol Sci 17
Suppl 1: 2–8.
a. Determine the frequency of HAP and the effect of isolation rooms on the frequency of
pneumonia in the ICU. The ICU, which was 4-bed ward-type between January 2004 and
February 2006 (1st period), was reconfigured as isolated rooms with only 2 beds each
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after March 2006 (2nd period); 153 and 379 patients were studied in the ICU in the 1st
and 2nd periods, respectively. Blood, sputum, and deep tracheal aspiration cultures
were used for the isolation of the causative agents. The prevalence of HAP was 22.9% in
the 1st period and 17.4% in the 2nd period.
Connelly SM, Trinh JV, Johnson MD, Dodds-Ashley ES, Stout J, Engemann JJ, et al. (2009)
Mortality and time to extubation in severe hospital-acquired pneumonia. Am J Infect Control 37:
143–149. doi:10.1016/j.ajic.2008.03.011 PMID: 18834753.
a. Patients with HAP prospectively identified between June 2001 and May 2003 were
included in the study if they (1) met the Centers for Disease Control and Prevention's
definition for HAP, (2) were treated in the ICU within 1 day of the HAP diagnosis, and (3)
required intubation acutely or had a bloodstream infection within 48 hours of the HAP
diagnosis. The cohort included 219 patients, 83 of whom died (37.9%).
Topal AE, Eren MN. (2012) Risk factors for the development of pneumonia post cardiac surgery.
Cardiovasc J Afr 23: 212–215. PMID: 22614666
a. The objective of this study was to identify potential risk factors for the development of
nosocomial pneumonia post cardiac surgery by the way of logistic regression analysis.
Postoperative pneumonia was diagnosed in 21 (13%) patients.
Oliveira TF, Gomes Filho IS, Passos Jde S, Cruz SS, Oliveira MT, Trindade SC, et al. (2011) Factors
associated with nosocomial pneumonia in hospitalized individuals. Rev Assoc Med Bras 57: 630–
636. PMID: 22249541
a. The goal of this study was to identify factors associated with nosocomial pneumonia in
individuals admitted to a public hospital in Feira de Santana, Bahia. This case control
study was carried out in 211 adult individuals (46 cases and 165 controls), of a mean age
of 41 years, treated at clinical wards, surgical wards or the adult ICU of Cleriston
Andrade General Hospital in Feira de Santana. The frequency of nosocomial pneumonia
in the sample was 21.8%. The occurrence of hypertension was higher and hospital stay
duration was longer in the cases than in controls (p ≤ 0.05).
Mor A, Thomsen RW, Ulrichsen SP, Sorensen HT. (2013) Chronic heart failure and risk of
hospitalization with pneumonia: a population-based study. Eur J Intern Med 24: 349–353. doi:
10.1016/j.ejim.2013.02.013 PMID: 23510659
a. CHF may increase risk of pneumonia due to alveoli flooding and reduced microbial
clearance. Researchers examined whether CHF is a risk factor for pneumonia-related
hospitalization. The study included 67,162 patients with a pneumonia-related
hospitalization and 671,620 population controls. Patients with CHF, in particular those
using loop diuretics, have markedly increased risk of hospitalization with pneumonia.
Masrur S, Smith EE, Saver JL, Reeves MJ, Bhatt DL, Zhao X, et al. (2013) Dysphagia screening and
hospital-acquired pneumonia in patients with acute ischemic stroke: findings from Get with the
Guidelines— Stroke. J Stroke Cerebrovasc Dis 22: e301–309. doi:
10.1016/j.jstrokecerebrovasdis.2012.11.013 PMID: 23305674
a. Among 314,007 ischemic stroke patients at 1244 Get with the Guidelines-Stroke
hospitals from 2003-2009 who were eligible for DS and had completed HAP data, 68.9%
underwent DS and 5.7% developed HAP. Patients with HAP were older, had admission
National Institutes of Health Stroke Scale score, were more likely to undergo DS (75.5%
to 68.5%), and increased length of stay and in-hospital mortality (12.4% to 2.3%).
Soto-Gomez N, Anzueto A, Waterer GW, Restrepo MI, Mortensen EM. (2013) Pneumonia: an
arrhythmogenic disease? Am J Med 126: 43–48. doi: 10.1016/j.amjmed.2012.08.005 PMID:
23177550
a. Researchers conducted a national cohort study using Department of Veterans Affairs
administrative data including patients aged ≥65 years hospitalized with pneumonia in
2002-2007, receiving antibiotics within 48 hours of admission, having no prior diagnosis
of a cardiac arrhythmia, and having at least 1 year of VA care. Researchers identified
32,689 patients who met the inclusion criteria. 3919 (12%) had a new diagnosis of
cardiac arrhythmia within 90 days of admission. Variables significantly associated with
increased risk of cardiac arrhythmia included increasing age, history of CHF, and need
for mechanical ventilation or vasopressors. β-blocker use was associated with a
decreased incidence of events.
The impact of hospital-acquired infections with multidrug-resistant bacteria in an oncology intensive
care unit
The goal of this study was to describe the overall site-specific hospital-acquired infection (HAI) rates as
well as describe microbiological and antibiotic resistance profiles of the infecting pathogens, together
with their impact on multidrug-resistant (MDR) bacteria-associated mortality. This data was gathered
through a 5-year retrospective descriptive study of HAI in patients in the intensive care unit (ICU) of a
cancer center in Mexico from January 2007 to December 2011. During the study period, 1418 patients
were admitted to the ICU; 134 of them developed 159 infections, with an incidence of 11.2/100
hospitalized patients and 32.2/1000 patient-days. Of these patients, 266 microorganisms were isolated.
The overall prevalence of MDR-HAI was 39.5% with the most frequent organisms were as follows: 20%
Escherichia coli, 12% Staphylococcus aureus, 12% Enterococcus faecium, and 6% Acinetobacter
baumannii; all had statistically significant populations that were MDR. Among patients admitted to the
ICU, 17.8% died. Death was related to the HAI in 23% of these patients and 51 88% had a MDR organism
isolated (p = 0.05). MDR bacteria poses a difficult task for physicians due to limited therapeutic options.
Critically ill cancer patients admitted to the ICU are at major risk of a bacterial MDR- HAI that will impact
adversely on mortality.
References
1. El-Ageery SM, Abo-Shadi MA, Alghaithy AA, Ahmad MA, Alsharif NH, Alharbi SA. Epidemiological
investigation of nosocomial infection with multidrug-resistant Acinetobacter baumannii. Eur Rev
Med Pharmacol Sci 2012; 16:1834–9.
a. MDR Acinetobacter baumannii, (MRAB) is an important cause of hospital acquired
infection. The aim of this study was to document the emergence of MRAB in an ICU and
to characterize hospital-wide outbreak by investigating antibiotypes and genotypes. A 6month study for the presence of MRAB infection or colonization on inpatients, health
care workers and environmental sites was done at an ICU in Fahd Hospital, Saudi Arabia.
A total 18 MRAB were isolated from 12 patients and 3 environmental samples.
2. Consales G, Gramigni E, Zamidei L, Bettocchi D, De Gaudio AR. A multidrug-resistant
Acinetobacter baumannii outbreak in intensive care unit: antimicrobial and organizational
strategies. J Crit Care 2011; 26:453–9.
a. MDR Acinetobacter baumannii (MRAB) is an emerging cause of ICU outbreaks with
patients as the main reservoirs, inducing cross transmission. The ICU consists of 2
separated 4-bed rooms. The MRAB-positive patients were included in the study. During
the outbreak, infection control measures were enhanced; patients and environmental
screenings were performed. 4 of 26 patients admitted during the outbreak were MRAB
positive; All patients received tigecycline: 2 were successfully treated, 1 died because of
preexisting illness, and 1 developed resistance and recovered after colistin therapy.
3. Prabaker K, Weinstein RA. Trends in antimicrobial resistance in intensive care units in the United
States. Curr Opin Crit Care 2011; 14:472–9.
a. This review focuses on the major epidemiologic trends and novel treatments, when
available, for MRSA, vancomycin-resistant enterococcus, Clostridium difficile, and MDR
Gram-negative bacilli in the United States during 2010-2011. Antimicrobial resistance,
particularly among Gram-negative bacilli, continues to increase at a rapid rate. Given
the frequent transfer of patients between outpatient and acute care settings, as well as
between geographic regions, coordinated infection control interventions are warranted.
4. Kamboj M, Sepkowits KA. Nosocomial infections in patients with cancer. Lancet Oncol 2009;
10:589–97.
a. Nosocomial infections become evident 48 hours or more after a patient is admitted for
treatment in a hospital. They cause substantial morbidity and mortality in patients who
are immunosuppressed. Understanding of host vulnerability has improved and more
rigorous management and infection-control practices have been adopted for treating
susceptible populations. Despite efforts, outbreaks continue to occur. In this review,
researchers outline knowledge of the incidence and microbiology of various nosocomial
infections in patients with cancer-a large, immunosuppressed population.
5. Agodi A, Zarrilli R, Barchitta M, Anzaldi A, Di Popolo A, Mattaliano A, et al. Alert surveillance of
intensive care unit-acquired Acinetobacter infections in a Sicilian hospital. Clin Microbiol Infect
2006; 12:241–7.
a. The epidemiological impact of Acinetobacter baumannii nosocomial infections in a
Sicilian ICU was investigated to determine the Acinetobacter-specific infection rates, to
estimate the preventable proportion of Acinetobacter infections. The impact of
Acinetobacter nosocomial infection in the ICU was determined to be 3.0 new cases per
100 admissions. Site-specific rates confirmed that ICU-acquired pneumonia was the
most important infection type. Even in an endemic setting with low infection rates,
spread of A. baumannii was caused mainly by infection control shortcomings that
require appropriate surveillance and control policies.
6. Cornejo-Jua´ rez P, Pe´ rez-Jime´nez C, Silva-Sa´nchez J, Vela´zquez-Acosta C, Gonza´ lez-Lara F,
Reyna-Flores F, et al. Molecular analysis and risk factors for Escherichia coli producing extendedspectrum beta-lactamase bloodstream infection in hematological malignancies. PLoS One 2012;
7:e35780. http:// dx.doi.org/10.1371/journal. pone.0035780.
a. Patients with hematologic malignancies have greater risk-factors for primary BSI. From
2004-2009, this study analyzed bacteremia caused by extended-spectrum betalactamase Escherichia coli (n = 100) and compared with bacteremia caused by
cephalosporin-susceptible E. coli (n = 100) in patients with hematologic malignancies.
Patients who had been previously hospitalized and who received cephalosporins during
the previous month, have an increased risk of ESBL-EC bacteremia. Mortality was
significantly increased in patients with ESBL-EC BSI. A polyclonal trend was detected,
which reflects non-cross transmission of MDR E.coli isolates.
7. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial
susceptibility testing. 13th Informational supplement, Vol. 25, No. 26. Approved Standard M2A7. Wayne, PA: CLSI; 2006.
8. Erbay H, Yalcin AN, Serin S, Turgut H, Tomatir E, Cetin B, et al. Nosocomial infections in intensive
care unit in a Turkish university hospital: a 2-year survey. Intensive Care Med 2003; 29:1482–8.
a. The goal of this study was to determine epidemiology and risk factors for nosocomial
infections in ICU. The study included 434 patients (7394 patient-days). A total of 225
infections were identified in 113 patients (26%). The incidence and infection rates were
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56.8 in 1000-patient days and 51.8%, respectively. These data suggest that, in addition
to underlying clinical conditions, some invasive procedures can be independent risk
factors for nosocomial infection in ICU.
Ylipalosaari P, Ala-Kokko TI, Laurila J, Ohtonen P, Syrja¨laa¨ H. Intensive care acquired infection
is an independent risk factor for hospital mortality: a prospective control study. Crit Care 2006;
10:R66.
a. The aim of this study was to illuminate the impact of ICU-acquired infection on hospital
mortality. Patients with a longer than 48 hour stay in a mixed 10 bed ICU in a tertiarylevel teaching hospital were prospectively enrolled between May 2002 and June 2003.
Risk factors for hospital mortality were analyzed with a logistic regression model. Of 335
patients, 80 developed ICU-acquired infection. Among the patients with ICU-acquired
infections, hospital mortality was always higher, regardless of whether or not the
patients had had infection on admission. ICU-acquired infection was an independent risk
factor for hospital mortality even after adjustment for the APACHE II or SOFA scores and
age.
Dettenkofer M, Ebner W, Els T, Babikir R, Lu¨ cking C, Pelz K, et al. Surveillance of nosocomial
infections in a neurology intensive care unit. J Neurol 2001; 248: 959–64.
a. To identify overall and site-specific nosocomial infection (NI) rates in patients receiving
neurological intensive care therapy, a prospective study was started in 1997 in the tenbed NICU of the University Hospital of Freiburg, Germany. Case records and
microbiology reports were reviewed twice a week, and ward staff were consulted. NI
were defined according to the CDC criteria and were categorized by specific infection
site. Within 30 months, 505 patients with a total of 4,873 patient days were studied. 122
NI were identified in 96 patients. An incidence of 24.2/100 patients and incidence
density of 25.0/1,000 patient days of NI in the neurological ICU were documented.
Montassier E, Batard E, Gastinne T, Potel G, de la Cochetie` re MF. Recent changes in bacteremia
in patients with cancer: a systematic review of epidemiology and antibiotic resistance. Eur J Clin
Microbiol Infect Dis 2013; 32:841–50.
a. Bacteremia remains a major cause of life-threatening complication in patients with
cancer. Significant changes in the spectrum of microorganisms isolated from blood
culture have been reported in cancer patients over the past years. The aim of our
systematic review was to inventory the recent trends in epidemiology and antibiotic
resistance of microorganisms causing bacteremia in cancer patients. Reporting the
recent findings in epidemiology and antibiotic resistance of bacteremia in cancer
patients, highlights the necessity of local continuous surveillance of bacteremia and
stringent enforcement of antibiotic stewardship programs in cancer patients.
Neidell NJ, Cohen B, Furuya Y, Hill J, Jeon CY, Glied S, et al. Costs of healthcare-and communityassociated infections with antimicrobial-resistant versus antimicrobial-susceptible organisms.
Clin Infect Dis 2012; 55:807–15.
a. Researchers compared differences in the hospital charges, length of hospital stay, and
mortality between patients with healthcare- and community-associated bloodstream
infections, urinary tract infections, and pneumonia due to antimicrobial-resistant versus
-susceptible bacterial strains. A retrospective analysis of an electronic database
compiled from laboratory, pharmacy, surgery, financial, and patient location and device
utilization sources was undertaken on 5699 inpatients who developed healthcare- or
community-associated infections between 2006 and 2008 from 4 hospitals (1
community, 1 pediatric, 2 tertiary/quaternary care) in Manhattan. Controlling for
multiple confounders using linear regression and nearest neighbor matching based on
propensity score estimates, resistant healthcare- and community-associated infections,
when compared with susceptible strains of the same organism, were associated with
significantly higher charges ($15,626; confidence interval, $4339-$26,913 and $25,573;
CI, $9331-$41,816, respectively) and longer hospital stays for community-associated
infections (3.3; CI, 1.5-5.4). Patients with resistant healthcare-associated infections also
had a significantly higher death rate (0.04; CI, 0.01-0.08).
Vitamin D Status and the Risk for Hospital-Acquired Infections in Critically Ill Adults: A Prospective
Cohort Study
The goal of this study was to identify patient characteristics associated with low vitamin D
concentrations in the medical intensive care unit (ICU) and examine the potential relationship between
vitamin D and the risk for hospital-acquired infections (HAI). This observational cohort studied adult
patients admitted to the medical ICU at an urban safety net teaching hospital in Atlanta, Georgia from
November 1, 2011 through October 31, 2012 with an anticipated ICU stay more than 1 day. Phlebotomy
for vitamin D was performed on all patients within 5 days of ICU admission. Patients were followed for
30 days or until death or hospital discharge (whichever came first). HAIs were determined using
standardized criteria from review of electronic medical record. Among the 314 patients analyzed, 57%
had a low vitamin D. A total of 11% of patients were decided as having a HAIs. In multivariable analysis
adjusting for gender, alcohol use, APACHE II score, time to study phlebotomy, ICU length of stay and net
fluid balance, low vitamin D levels were not associated with risk for hospital-acquired infections.
References
1. Vincent JL, Bihari DJ, Suter PM, Bruining HA, White J, Nicolas-Chanoin MH, et al. The prevalence
of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of
Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee. JAMA. 1995;
274: 639–644. PMID: 7637145
a. To determine the prevalence of ICU-acquired infections and the risk factors for these
infections, identify the predominant infecting organisms, and evaluate the relationship
between ICU-acquired infection and mortality. Intensive care units in 17 countries in
Western Europe, excluding coronary care units and pediatric and special care infant
units were studied looking at All patients (> 10 years of age) occupying an ICU bed over
a 24-hour period. A total of 1417 ICUs provided 10 038 patient case reports. A total of
4501 patients (44.8%) were infected, and 2064 (20.6%) had ICU-acquired infection.
Pneumonia (46.9%), lower respiratory tract infection (17.8%), urinary tract infection
(17.6%), and bloodstream infection (12%) were the most frequent types of ICU infection
reported. CU-acquired infection is common and often associated with microbiological
isolates of resistant organisms. The potential effects on outcome emphasize the
importance of specific measures for infection control in critically ill patients.
2. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated
infection and criteria for specific types of infections in the acute care setting. Am J Infect
Control. 2008; 36: 309–332. doi: 10.1016/j.ajic.2008.03.002 PMID: 18538699
3. Jeng L, Yamshchikov AV, Judd SE, Blumberg HM, Martin GS, Ziegler TR, et al. Alterations in
vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with
sepsis. J Transl Med. 2009; 7: 28. doi: 10.1186/1479-5876-7-28 PMID: 19389235
a. Vitamin D insufficiency is common in hospitalized patients. Recent evidence suggests
that vitamin D may enhance the innate immune response by induction of cathelicidin
(LL-37), an endogenous antimicrobial peptide produced by macrophages and
neutrophils. This study demonstrates an association between critical illness and lower
25(OH)D and DBP levels in critically ill patients as compared to healthy controls. It also
establishes a positive association between vitamin D status and plasma LL-37, which
suggests that systemic LL-37 levels may be regulated by vitamin D status. Optimal
vitamin D status may be important for innate immunity especially in the setting of
sepsis. Further invention studies to examine this association are warranted.
4. Su LX, Jiang ZX, Cao LC, Xiao K, Song JP, Camargo CA. Significance of low serum vitamin D for
infection risk, disease severity and mortality in critically ill patients. Chin Med J (Engl). 2013; 126:
2725–2730. PMID: 23876904
a. Hospitalized patients often have higher rate of vitamin D deficiency than healthy people.
Vitamin D levels below normal are associated with hospital stay, increased incidence of
adverse prognosis and increased mortality of a number of diseases. To evaluate the
value of vitamin D in ICU cases to sepsis, severity and prognosis assessment, high
performance liquid chromatography and tandem mass spectrometry were used to
measure the concentrations of vitamin D in sera of critically ill patients. The study
included 206 people, 50 healthy controls, 51 ICU control patients and 105 ICU diagnosed
with sepsis. Critically ill ICU patients had lower vitamin D concentration than normal
people, but septic patients showed no significant reduction of vitamin D concentration
when compared with critically ill patients. Serum concentration of vitamin D is not an
indicator for diagnosis and assessment in critically ill patients.
5. Quraishi SA, Litonjua AA, Moromizato T, Gibbons FK, Camargo CA Jr, Giovannucci E, et al.
Association Between Prehospital Vitamin D Status and Hospital-Acquired Clostridium difficile
Infections. J Parenter Enteral Nutr. 2015; 39: 47–55 doi: 10.1177/0148607113511991 PMID:
24492311
a. To investigate whether preadmission 25-hydroxyvitamin D (25(OH)D) levels are
associated with the risk of hospital-acquired Clostridium difficile infection
(HACDI).Materials and Methods: The retrospective cohort study focused on 568 adult
patients from 2 Boston teaching hospitals between August 1993 and November
2006. In this cohort of adult patients, vitamin D status before hospital admission was
inversely associated with the risk of developing HACDI. These data support the need for
randomized, controlled trials to test the role of vitamin D supplementation to prevent
HACDI.
6. Turner J, Cho Y, Dinh NN, Waring AJ, Lehrer RI. Activities of LL-37, a cathelin-associated
antimicrobial peptide of human neutrophils. Antimicrob Agents Chemother. 1998; 42: 2206–
2214. PMID: 9736536
a. Human neutrophils contain two structurally distinct types of antimicrobial peptides,
beta-sheet defensins (HNP-1 to HNP-4) and the alpha-helical peptide LL-37. We used
radial diffusion assays and an improved National Committee for Clinical Laboratory
Standards-type broth microdilution assay to compare the antimicrobial properties of LL37, HNP-1, and protegrin (PG-1). Although generally less potent than PG-1, LL-37
showed considerable activity (MIC, <10 microgram/ml) against Pseudomonas
aeruginosa, Salmonella typhimurium, Escherichia coli, Listeria monocytogenes,
Staphylococcus epidermidis, Staphylococcus aureus, and vancomycin-resistant
enterococci, even in media that contained 100 mM NaCl. The potent activity of LL-37
against P. aeruginosa, including mucoid and antibiotic-resistant strains, suggests that it
or related molecules might have utility as topical bronchopulmonary microbicides in
cystic fibrosis.
7. Nijnik A, Hancock RE. The roles of cathelicidin LL-37 in immune defenses and novel clinical
applications. Curr Opin Hematol.2009; 16: 41–47. PMID: 19068548
a. LL-37 is the only member of the cathelicidin family of host defence peptides expressed
in humans. It is primarily produced by phagocytic leucocytes and epithelial cells, and
mediates a wide range of biological responses: direct killing of microorganisms,
chemotaxis and chemokine induction, regulation of inflammatory responses, as well as
adjuvant, angiogenic and wound healing effects. The understanding of the biological
properties and functions of LL-37 and other host defence peptides advances our
knowledge of innate immunity, the interactions of the host with pathogens and the
microflora, as well as the pathology of infectious and inflammatory diseases, creating
many strategies and opportunities for therapeutic intervention.
8. Hewison M. Antibacterial effects of vitamin D. Nat Rev Endocrinol. 2011; 7: 436. doi:
10.1038/nrendo.2011.105 PMID: 21691306
a. Interaction between vitamin D and the immune system has been recognized for many
years, but its relevance to normal human physiology has only become evident in the
past 5 years. Studies of innate immune responses to pathogens such as Mycobacterium
tuberculosis have shown that pathogen-recognition receptor-mediated activation of
localized vitamin D metabolism and signaling is a key event associated with infection.
This Review will explore the molecular and cellular systems associated with antibacterial
responses to vitamin D in different tissues and possible consequences of such a
response for the prevention and treatment of human immune disorders.
9. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D: modulator of the immune
system. Curr Opin Pharmacol. 2010; 10: 482–496. doi: 10.1016/j.coph.2010.04.001 PMID:
20427238
a. 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the active form of vitamin D, is known to
regulate calcium and phosphorus metabolism, thus being a key-player in boneformation. However 1,25(OH)(2)D(3) also has a physiological role beyond its well-known
role in skeletal homeostasis. Besides being targets, immune cells express vitamin Dactivating enzymes, allowing local conversion of inactive vitamin D into 1,25(OH)(2)D(3)
within the immune system. Several epidemiological studies have linked inadequate
vitamin D levels to a higher susceptibility of immune-mediated disorders, including
chronic infections and autoimmune diseases. This review will discuss the complex
immune-regulatory effects of 1,25(OH)(2)D(3) on immune cells as well as its role in
infectious and autoimmune diseases, more in particular in tuberculosis and type 1
diabetes (T1D).
10. Leaf DE, Raed A, Donnino MW, Ginde AA, Waikar SS. Randomized controlled trial of calcitriol in
severe sepsis. Am J Respir Crit Care Med. 2014; 190: 533–541. doi: 10.1164/rccm.2014050988OC PMID: 25029202
a. Researchers investigated whether administration of 1,25-dihydroxyvitamin D (calcitriol)
to critically ill patients with sepsis would have beneficial effects on markers of innate
immunity, inflammation, and kidney injury. They performed a double-blind,
randomized, placebo-controlled, physiologic study among 67 critically ill patients with
severe sepsis or septic shock. Patients were randomized to receive a single dose of
calcitriol versus placebo. Calcitriol administration did not increase plasma cathelicidin
protein levels in critically ill patients with sepsis and had mixed effects on other
immunomodulatory markers.