candida infections in surgical patients
TRANSCRIPT
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Tsikrikonis Giorgos
Department of Microbiology, Hippokration
General Hospital of Thessaloniki, Greece
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Candida infections remain an important cause ofmorbidity and mortality in surgical settings.
Surgical patients are at particular risk for fungalinfection: more than 50% of all fungal infectionsoccur in this patient population.
Data from the NNIS indicated that in the periodfrom 1989 to 1998 C. albicans was the seventh mostcommon cause of nosocomial infection in the ICUsetting, accounting for 4.9% of bloodstream
infections and 4.8% of surgical site infections.
Candida species(spp) have emerged as the fourthmost common bloodstream pathogen in thecritically ill with an associated mortality rate of 19-
50%.
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Nosocomial Blood Stream Infections, NationalNosocomial Infection Surveilance System (NNIS)1985-1988
Rank 1988 Pathogen Percent Rank 1984
1 Coag-neg Staph 25.5 1
2 S. aureus 15.0 2
3 Enterococci 7.9 6
4 Candidaspp. 7.7 8
5 E. coli 6.8 3
6 Enterobacter 5.2 77 P. aeruginosa 5.0 5
8 Klebsiella spp. 4.4 4
Horan T, et al. Antimicrob Newsletter 5:56, 1988
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Underlying Conditions ImmuneDefects
Iatrogenic Factors
Burns, disruption ofcutaneous or mucosal
barriers Cancer Candidacolonization Cytomegalovirus (CMV) Diabetes mellitus
Graft versus host disease Hematological malignancies HIV, DIC, Shock Malnutrition Organ transplantation
(liver, pancreas and small
bowel in particular)
Granulocytopenia
Neutropenia T-cell
defects
Broad-spectrumantibiotics
Central venouscatheters
Chemotherapy High-dose steroids Immunosuppressive
therapy Intra-abdominal (GI)
surgery Total parenteral
nutrition Longer stays in the
ICU
Risk factors for the development ofCandidainfections can be broken
down into three components :
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The most common types of candidainfections in surgical patients are:
candidemia,
secondary peritonitis
surgical wound infection and
urinary tract infection
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Candidemia is the fourth most common
nosocomial bloodstream infection in the UnitedStates. The attributable mortality rate is 33-47%for invasiveCandida infections, which issignificantly higher than the mortality rate for
the other major causes of nosocomialbloodstream infections.
Central venous catheters are well documentedas independent risk factors for the developmentof candidemia. C. albicansandC. parapsilosisare the most commonly associatedCandida spp.with the production of biofilms on invasivedevices, which renders them nearly completely
resistant to antifungal therapy.
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Candida is either the most common or thesecond most common pathogen isolated fromthe urine in surgical ICU patients. The termurinary candidiasis refers to an ill-defined
group of syndromes, many of which probablyrepresent colonization rather than infection.
Candiduria is very common in hospitalizedpatients who have urinary catheters in placefor more than 14 days. In this setting it ismore likely to reflect colonization thaninfection.
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Candidal Endopthalmitis: Usually implieshematogenous spread to multiple organs.Identification of eye involvement early in therapy iscrucial for preserving visual activity.
Suppurative thrombophlebitis: Results frominfection of a vessel traumatized by prolongedcatheterization.
Endocarditis: Candida endocarditis is very difficultto treat. The overall outcome of candidainfectiveendocarditis is grim, carrying a reported mortalityof up to 80%.
Pericarditis: The surgical patients at risk forpurulent pericarditis caused by Candidaare thosewho have undergone a cardiac operation, those whohave a malignancy and whose host defenses areimpaired and those who have a debilitating chronic
disease.
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Arthritis :Candida joint infections tend to occur in
patients with rheumatoid arthritis or prosthetic jointdevices. Osteomyelitis:Except for sternal infections
complicating median sternotomy, most cases ofcandidal osteomyelitis develop through hematogenous
spread. Meningitis:Candidal meningitis may followhematogenous spread, or it may be a complication ofa neurosurgery or the implantation ofventriculoperitoneal shunts. The infection is insidiousand sometimes goes undiagnosed. Most patients withcandidal meningitis have recently receivedantibacterial agents, and half have previously hadbacterial meningitis.
Pneumonia:True candidal pneumonia is rare, but itcan occur through hematogenous dissemination into
the lung as one of many sites of infection.
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Culture: The workup of a surgical patient withsuspected hematogenous candidiasis begins witha complete set of cultures of sputum,oropharynx, stool, urine, all drain sites, and
blood. A rapid and inexpensive test is the germ tube
test(formation of filamentous extensions fromyeast cells in a serum suspension of yeast),which can distinguish C. albicans (positive result)
from other Candidaspecies. Positive cultures from nonsterile sites (sputum,
urine, and wound drainage) must be interpretedwith caution because of the frequent occurrenceof Candida as a normal commensal of humans
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Histologic analysis: Analysis of fungal smears is arelatively insensitive method of diagnosingcandidiasis and other fungal infections inotherwise sterile sites (e.g. joint fluid,peritoneal fluid, vitreous humor, or
cerebrospinal fluid). Centrifugation of these fluids and examination
of the sediment may improve the diagnosticyield.
Conventional fungal stains, such as hematoxylin-
eosin, periodic acid-Sciff (PAS), and Gomorimethenamine-silver (GMS), are useful. The mostsensitive stain is calcofluor white, butunfortunately it requires fluorescent microscopy.Deep tissue biopsy provides a definitive diagnosis
of candidiasis.
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Candida albicansis the most commonly isolatedCandida spp.Most C. albicans isolates aresensitive to all of the currently availableagents, but some low-level resistance has been
reported, especially with previous long-termexposure to azoles at low dosages. However, the increasing emergence of non-
albicans Candida spp. poses a significant threat
to an older and more immunocompromisedpopulation. Candida glabrata, Candida
tropicalis,andCandida parapsilosisare the
most commonly isolatednon-albicansspecies.
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The concern with the increasing number ofCandida non-albicansspecies is that anti-fungal susceptibility patterns vary based onthe specificCandida spp.
For example,C. lusitanie may be resistant toamphotericin B, C. kruseiis intrinsicallyresistant to fluconazole andC. glabrataexhibits dose-dependant susceptibility tofluconazole (i.e., requires higher doses to
effectively treat). Identifying the specific species ofCandida
isolated makes a significant impact onantifungal therapy decisions.
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Species Polyene Azole Echinocandin
Ampho B Flucon Vori Posa Caspo Anid
C. albicans S S S S S SC. glabrata S to I S-DD to R S - S-DD S - S-DD S S
C. krusei S to I R S - S-DD S - S-DD S S
C. lusitaniae R S S S S S
C. parapsilosis S S S S I I
C. tropicalis S S S to I S S S
Ampho B = amphotericin B, Flucon = filuconazole, Vori = voriconazole,Posa = posaconazole, Caspo = caspofungin, Anid = anidulafungin. S =
sensitive, S-DD = sensitive dose-dependent, I = intermediate, R = resistant
The following table reflects the susceptibility profiles of the more commonCandida spp.
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Our objective was to study the frequency and typesof Candida infections that surgical patients developed
in our hospital over the last three years.
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We retrospectively studied allnon-immunosuppressedpatients who underwentsurgery and developed an
infection caused by Candidaspecies over the last 3 yearsin Hippokration GeneralHospital of Thessaloniki.
All the samples wereinoculated for culture inSabouraud dextrose agar(SDA) and incubated at 37Cfor 24-72 hours.
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Germ tube test:A sample of fungalspores are suspended in
serum. Incubate the testat 350C for 2.5-3 hours.Examine by microscopyfor the detection of anygerm tubes.
Candida albicanswas identified by the germtube test.
Non-albicansspecies that were isolated fromblood cultures were identified using the VITEK2
system (bioMrieux).
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:
A total of 4279 patients had some type ofpostoperative infections, 591 (13.8 %) of
whom developed a Candidainfection.
Candida albicanswas isolated from 53.5 % of
the infected with Candida patients. Non-
albicans species were detected in 46.5 % ofthe positive cultures for Candida.
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The site of isolation of Candidaisolates was:
67.5 % from urine,
12.7 % from surgical wounds, 10.2 % from blood and
at proportions of 4.5 %, 3.7 % and 1.4 %
from peritoneal fluid, central venous
catheters and other sources respectively.
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:
As for candidemiasall species isolated wereCandida non-albicans.
Analysis of all positive blood cultures for
Candidayielded detection of:
Candida parapsilosis in51.4 %,
Candida tropicalisin 21.6 %,
Candida famata in21.6 %and
Candida glabrata in 5.4 %.
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Candidainfections represent a significant
proportion of the infections that surgical patientsdeveloped in our hospital (13.8 % of infectionswere due to Candidaspecies).
The frequency of isolation of non-albicans strains
was significant (46.5 % of the positive cultures forCandida).
At ORMC, a review ofCandidaisolates from blood
and urine cultures from July 2006 through June
2007 revealed a nearly 50:50 splitC. albicans to
non-albicans(52%C. albicans,48%Candida non-
albicans) similar to our study.
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Marsch et al, 1983
Few studies have investigated the characterization typesof candidainfections in surgical patients.
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Compared with the 1980s, a larger proportion of
Candida BSI is now caused by Candida glabrata inthe United States and by Candida parapsilosis andCandida tropicalis in European, Canadian, and LatinAmerican hospitals.
This change in the most frequent cause ofcandidemia has been explained in part by the highaffinity of C. parapsilosis for intravascular devicesand parenteral nutrition and their widespread use.
The increasing use of antifungal agents to preventrisk patients might also have favored changes in thespecies causing infections. Nosocomial outbreaks ofC. parapsilosis have also been described previously,and the hands of healthcare workers may be the
predominant environmental source.
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Candida has been the commonest fungal pathogen
described in surgical patients in previous studies. Anincreasing number of serious Candidainfections has
been noted on surgical services in recent years.
This increase may be related to improvements in
surgical technique and perioperative care that allow
high-risk patients to survive, despite serious
underlying diseases. The price for increased survival
is the propensity to develop unusual infections.
The important risk of Candida infections in surgical
patients requires vigilance and probably an early
start of antifungal therapy in patients at high risk.
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