candida infections in surgical patients

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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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