Polymicrobial bloodstream infections involving Candida species: analysis of patients and review of the literature

Candida species are the 4th most common cause of nosocomial bloodstream infections in North America. It is not widely appreciated, however, that many of these infections are polymicrobial, that is, that bacteria and occasionally more than 1 species of Candida are present in the same blood culture bottle. Analysis of 2 groups of candidemic patients and a review of the literature were performed. Review of 141 candidemic patients from 8 Veterans Affairs hospitals and 231 patients from a tertiary care hospital with transplant services was performed. Of the 372 patients with candidemia, 100 (27%) had polymicrobial blood cultures: 88 patients (24%) had synchronous bacteremia and 12 patients (3%) had more than 1 species of Candida. One hundred bacteria were isolated from these patients, 69 were Gram positive, and 31 were Gram negative. Candidemia was shown to occur in a setting of polymicrobial bacteremia extending over days, whereas Staphylococcus aureus and coagulase-negative Staphylococcus were less frequently associated with polymicrobial bloodstream infections. Review of more than 8000 reported episodes of candidemia revealed high rates of polymicrobial infection occurring with candidemia. Of blood cultures isolating Candida, 23% were polymicrobial and 4% had more than 1 species of Candida. Thus, almost 1 in 4 patients with candidemia will have a polymicrobial bloodstream infection. As detection of bloodborne infections evolves toward nonculture methodologies, documentation of the frequency of polymicrobial bloodstream infections involving Candida is important. This finding may have treatment implications for clinicians.     

Efficacy of Ethanol against Candida albicans and Staphylococcus aureus Polymicrobial Biofilms

Candida albicans, an opportunistic fungus, and Staphylococcus aureus, a bacterial pathogen, are two clinically relevant biofilm-forming microbes responsible for a majority of catheter-related infections, with such infections often resulting in catheter loss and removal. Not only do these pathogens cause a substantial number of nosocomial infections independently, but also they are frequently found coexisting as polymicrobial biofilms on host and environmental surfaces. Antimicrobial lock therapy is a current strategy to sterilize infected catheters. However, the robustness of this technique against polymicrobial biofilms has remained largely untested. Due to its antimicrobial activity, safety, stability, and affordability, we tested the hypothesis that ethanol (EtOH) could serve as a potentially efficacious catheter lock solution against C. albicans and S. aureus biofilms. Therefore, we optimized the dose and time necessary to achieve killing of both monomicrobial and polymicrobial biofilms formed on polystyrene and silicone surfaces in a static microplate lock therapy model. Treatment with 30% EtOH for a minimum of 4 h was inhibitory for monomicrobial and polymicrobial biofilms, as evidenced by XTT {sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide inner salt} metabolic activity assays and confocal microscopy. Experiments to determine the regrowth of microorganisms on silicone after EtOH treatment were also performed. Importantly, incubation with 30% EtOH for 4 h was sufficient to kill and inhibit the growth of C. albicans, while 50% EtOH was needed to completely inhibit the regrowth of S. aureus. In summary, we have systematically defined the dose and duration of EtOH treatment that are effective against and prevent regrowth of C. albicans and S. aureus monomicrobial and polymicrobial biofilms in an in vitro lock therapy model.     

Candida infections in non-neutropenic children after the neonatal period

There are a variety of diseases, from local mucous membrane infections to invasive systemic infections, that are caused by Candida species. As a causative agent, Candida albicans is the most common; however, the other Candida species can also cause the same clinical syndromes. Most invasive fungal infections in children occur in the hospital setting. Candidemia is a serious condition associated with high morbidity and mortality and increased healthcare costs in pediatric patients. Children at the highest risk are those with prolonged intensive care unit stays, reduced immune function, recent surgery, prior bacterial infection, prior use of antibiotics and/or corticosteroids and other immunosuppressive agents, as well as use of a central venous catheter, total parenteral nutrition, mechanical ventilation and dialysis. Positive blood culture is the gold standard of candidemia; it should not be accepted as contamination or colonization in children with an intravascular catheter. However, in oropharyngeal or vulvovaginal candidiasis, culture of lesions is rarely indicated unless the disease is recalcitrant or recurrent. Recovery of Candida from the sputum should usually be considered as colonization and should not be treated with antifungal therapy. Antigen and antibody detecting tests are evaluated in invasive Candida infections; however, there are no published results in children, and their roles in diagnosis are also unclear. For the therapy of invasive Candida infections in non-neutropenic patients, fluconazole or an echinocandin is usually recommended. Alternatively, amphotericin B deoxycholate or lipid formulations of amphotericin B can also be used. The recommended therapy of Candida meningitis is amphotericin B combined with flucytosine. The combination therapy for Candida infections is usually not indicated. Prophylaxis in non-neonatal, immunocompetent children is not recommended.     

Staphylococcal bacteremia in cancer patients: Risk factors and outcome in 134 episodes prior to and after introduction of quinolones into infection prevention in neutropenia

A total of 134 episodes of staphylococcal bacteremia (SBE) appearing among 9987 admissions, and 979 episodes of bacteremia in cancer patients within 5 years, were analyzed for risk factors, clinical course and outcome; 64 were monomicrobial and 70 polymicrobial. The most frequent risk factors were acute leukemia, catheter insertion, long-lasting neutropenia, and prior prophylaxis with quinolones. There was no significant difference between polymicrobial and monomicrobial SBE in risk factors. The two groups differed only in the source of bacteremia (gastrointestinal and respiratory-tract infections were more common in monomicrobial SBE) and etiology —Staphylococcus aureus appeared more frequently in monomicrobial than in polymicrobial bacteremia (20.3% compared to 4.3%,P<0.05). More complications (14.3%) such as abscesses, endocarditis, etc. appeared in the group of polymicrobial SBE (P < 0.05). No difference was observed in clinical course and outcome between monomicrobial and polymicrobial SBE. The incidence of SBE has increased since 1991, when quinolones were first used in prophylaxis in afebrile neutropenia at our center; however, the infection-associated mortality in monomicrobial SBE was low (4.3%).     

真菌血症31例临床分析

目的对真菌血症的临床及微生物学特征进行分析,为临床诊治提供参考。方法收集2004年8月—2005年12月期间我院31例真菌血症患者的临床资料进行回顾分析。结果超过80%的真菌血症患者患有2种或以上的基础疾病。半数以上患者均有导管留置,而且83．9%患者在血培养采样前1周内均不同程度使用抗菌药物。31例真菌血症中,24例(77．4%)与念珠菌有关,但仅3例由白念珠菌引起,念珠菌血症患者的病死率为45．8%。不同念珠菌对抗真菌药物存在不同程度的耐药率。结论真菌血症多发生于基础疾病严重者,由非白念珠菌导致的败血症在真菌血症中占很大比例;部分真菌对氟康唑、伊曲康唑耐药。     

Persistence of the same Candida albicans strain despite fluconazole therapy. Documentation by pulsed-field gel electrophoresis.

Candida albicans and other Candida species have emerged as major nosocomial pathogens associated with a high mortality. Therapeutic options for fungal infections are limited. Amphotericin B has been the mainstay of treatment for serious systemic candidal infections, but it is relatively toxic and associated with a variety of side effects. Fluconazole has been proposed as alternative therapy for the treatment of systemic candidiasis including candidemia. We report the case of a patient with fungemia in whom fluconazole failed to eradicate C. albicans and C. tropicalis. These pathogens were recovered from sputum and urine cultures, respectively, on day 12 of intravenous fluconazole therapy. Molecular epidemiologic techniques employing pulsed-field gel electrophoresis confirmed the persistence of the same C. albicans strain. Susceptibility studies showed a marked change in MICs of fluconazole between 24 and 48 hr, with an increase from less than or equal to 1.25 to greater than 80 micrograms/ml. Controlled trials will be needed to delineate the role of fluconazole in the treatment of disseminated candidiasis and its efficacy in comparison with amphotericin B. Amphotericin B should remain the drug of choice for such infections until data from controlled trials are available.     

Characteristics and Outcomes of Polymicrobial Bloodstream Infections in the Emergency Department: A Matched Case–control Study

Objectives: Polymicrobial bloodstream infection (BSI) is a critical condition and has been increasingly reported; however, the authors were unable to find an emergency department (ED) patient‐based study in the literature. Methods: A retrospective matched case–control study with a ratio of 1:3 among patients with polymicrobial BSIs in an ED was conducted. The case group was patients aged > 16 years with polymicrobial BSIs. Patients matched for age and sex with monomicrobial BSIs were sampled as the control group. Demographic information, underlying conditions, microbiologic data, and outcomes were collected for further analysis. Results: From January 2005 to December 2007, a total of 112 episodes of polymicrobial BSIs among 109 patients were included. Two pathogens were isolated among 87 (77.7%) episodes and three were found among 25 (22.3%) episodes. A history of hospitalization within 90 days was an independent risk factor for polymicrobial BSIs (p = 0.003). Intraabdominal infection (p < 0.001) and respiratory tract infection (p = 0.017) were more likely to be associated with polymicrobial BSIs. Gram‐negative and Gram‐positive bacteria were documented in 95.5 and 46.4% episodes of polymicrobial BSIs, respectively. Inappropriate antimicrobial treatment was observed in 53.6% of polymicrobial BSIs, but only accounted for 23.8% of monomicrobial BSIs (p < 0.001). The overall 30‐day mortality rate of the polymicrobial group was significantly higher than those with monomicrobial BSIs (30.3 and 11.6%, respectively; p < 0.001). Conclusions: Patients with polymicrobial BSIs had a high mortality rate. Acknowledgment of the clinical and microbiologic characteristics and recognition of patients at risk for polymicrobial BSIs are critical in EDs. ACADEMIC EMERGENCY MEDICINE 2010; 17:1072–1079 © 2010 by the Society for Academic Emergency Medicine     

Candidemia in pediatric patients with congenital heart disease

Candidemia is an important problem in pediatrics. In our hospital, highest candidemia rates were documented among children with congenital heart disease (CHD). A series was conducted to describe the clinical and mortality features of candidemia in these patients. Fifty-two cases (1988-2000) included very young infants (median age, 2 months) who received long-term antibiotic treatment (median, 20.5 days). Candida parapsilosis predominated (54%). Endovascular infections occurred in 11.5%. In-hospital mortality was 39% and related mortality 14%. Maintenance of catheter (odds ratio [OR], 6.0; 95% confidence interval [CI], 1.0-37.2; P = .05) and severity of patients as measured with the Pediatric Risk Score of Mortality I (OR, 1.1, 95% CI, 1.0-1.3; P = .05) were independently associated with mortality. In summary, candidemia in children with CHD is diagnosed to very young infants with prolonged antibiotic therapy. Mortality is high but, in most cases, is not related to candidemia. Optimal management may include exclusion of endocarditis, early antifungal treatment, and catheter removal.     

An Analysis of Community and Hospital-acquired Bacteraemia in a Large Teaching Hospital in the United Kingdom

A total of 875 episodes of bacteraemia and fungaemia were analysedin patients admitted to University Hospital, Nottingham, andthree smaller hospitals over a four-year period. In 814 episodes(93 per cent) a single organism was isolated, most commonlyEscherichia coli (27.4 per cent), other enterobacteria (14.4per cent), Staphylococus aureus (11.2 per cent), Streptococcuspneumoniae (9.0 per cent), or Haemophilus influenzae (6.4 percent). In 61 cases (7.0 per cent) bacteraemia was due to twoor more species. In almost 60 per cent of cases, bacteraemiawas considered to be community-acquired. The most common sourceswere the urinary (26.9 per cent), respiratory (14.6 per cent),gastrointestinal (11.6 percent) and biliary (9.5 percent) tracts,but in almost 10 per cent of cases the focus of infection wasunknown. Polymicrobial bacteraemia was common when the biliarytract was the focus of infection. Shock was recorded in 19.5per cent of cases, and was commoner in polymicrobial (42.9 percent) than in monomicrobial (17.4 per cent) episodes. In monomicrobialepisodes haemolytic streptococci were associated with the highestincidence of shock (30.0 per cent). Mortality directly relatedto bacteraemia (19.5 per cent) was higher with Gram-positive(23.5 per cent) than with Gram-negative (15.8 per cent) organisms;in polymicrobial (31.1 per cent) than in monomicrobial episodes(18.7 per cent); and in those who had multiple episodes (34.7per cent) than in those who had a single episode of bacteraemia(20.3 per cent). Other factors influencing mortality includedshock, failure to mount an adequate febrile response, leucopeniaor granulocytopenia, and underlying disease. Mortality was markedlyreduced by appropriate treatment; a single antimicrobial agentwas as effective as combination therapy in bacteraemia causedby Gram-negative bacilli.     

Prior antimicrobial therapy and risk for hospital-acquired Candida glabrata and Candida krusei fungemia: a case-case-control study

The incidence of infections caused by Candida glabrata and Candida krusei, which are generally more resistant to fluconazole than Candida albicans, is increasing in hospitalized patients. However, the extent to which prior exposure to specific antimicrobial agents increases the risk of subsequent C. glabrata or C. krusei candidemia has not been closely studied. A retrospective case-case-control study was performed at a university hospital. From 1998 to 2003, 60 patients were identified with hospital-acquired non-C. albicans candidemia (C. glabrata or C. krusei; case group 1). For comparison, 68 patients with C. albicans candidemia (case group 2) and a common control group of 121 patients without candidemia were studied. Models were adjusted for demographic and clinical risk factors, and the risk for candidemia associated with exposure to specific antimicrobial agents was assessed. After adjusting for both nonantimicrobial risk factors and receipt of other antimicrobial agents, piperacillin-tazobactam (odds ratio [OR], 4.15; 95% confidence interval [CI], 1.04 to 16.50) and vancomycin (OR, 6.48; CI, 2.20 to 19.13) were significant risk factors for C. glabrata or C. krusei candidemia. For C. albicans candidemia, no specific antibiotics remained a significant risk after adjusted analysis. Prior fluconazole use was not significantly associated with either C. albicans or non-C. albicans (C. glabrata or C. krusei) candidemia. In this single-center study, exposure to antibacterial agents, specifically vancomycin or piperacillin-tazobactam, but not fluconazole, was associated with subsequent hospital-acquired C. glabrata or C. krusei candidemia. Further studies are needed to prospectively analyze specific antimicrobial risks for nosocomial candidemia across multiple hospital centers.     

Adequacy of empirical antifungal therapy and effect on outcome among patients with invasive Candida species infections

OBJECTIVES: Although inadequate antimicrobial therapy has been demonstrated in multiple studies to increase the risk for death in bacterial infections, few data investigating the effect of antifungal therapy on outcome of serious fungal disease are available. We sought to assess the adequacy of empirical therapy and its effect on mortality in invasive Candida species infections. METHODS: Population-based surveillance of all patients with Candida spp. cultured from blood and/or cerebrospinal fluid was conducted. Adequacy of empirical therapy was assessed according to published guidelines. RESULTS: During a 5 year period, 207 patients had an invasive Candida spp. infection identified; in 199 cases (96%) adequate data were available for assessment of treatment and outcome at hospital discharge. One hundred and three (52%) cases were due to Candida albicans, 44 (22%) were due to Candida glabrata and the remainder were due to other species. Between the time of culture draw and reporting of a positive culture, only 64 (32%) patients were treated with empirical therapy; this was deemed adequate in 51 (26%). Patients who received adequate empirical therapy had a significant decrease in crude mortality [14/51 (27%) versus 68/148 (46%); risk ratio 0.60 (95% confidence interval 0.37-0.96); P = 0.02]. After adjusting for age and the need for intensive care unit admission in logistic regression analysis, the use of adequate empirical therapy was independently associated with a reduced risk for death [odds ratio 0.46 (95% confidence interval 0.22-1.00); P = 0.05]. CONCLUSIONS: Adequate empirical therapy is used in a minority of patients with invasive Candida spp. infections but is associated with improved survival.     

Prevention of severe Candida infections in nonneutropenic,high-risk,critically ill patients: a randomized,double-blind,placebo-controlled trial in patients treated by selective digestive decontamination

OBJECTIVE: Infections caused by Candida spp. are a major cause of morbidity and mortality in critically ill patients and usually develop from endogenous colonization. We assessed the effectiveness of adding fluconazole to a selective digestive decontamination regimen to prevent candidal infections. DESIGN AND SETTING: We performed a prospective, randomized, double-blind, placebo-controlled trial among medical and surgical intensive care unit patients at a large university hospital. PATIENTS: All adult patients mechanically ventilated for at least 48 h with an expectation to remain so for at least an additional 72 h, and receiving selective decontamination of the digestive tract. INTERVENTIONS: Patients were randomly assigned fluconazole 100 mg daily (n=103) or placebo (n=101). MEASUREMENTS AND RESULTS: Candida infections occurred less frequently in the fluconazole group (5.8%) than in the placebo group (16%; rate ratio 0.35; Cl(95) 0.11-0.94). Some 90% of candidemia episodes occurred in the placebo group (rate ratio for fluconazole use 0.10; Cl(95) 0.02-0.74). The rate of treatment failure, development of candidal infection, or increased colonization, was 32% in the fluconazole group and 67% in the placebo group (P<0.001). Crude in-hospital mortality was similar in the two groups (39% fluconazole vs. 41% placebo). CONCLUSIONS: Prophylactic use of fluconazole in a selected group of mechanically ventilated patients at high risk for infection reduces the incidence of Candida infections, in particular candidemia.     

Serologic analysis of antigen-specific reactivity in patients with systemic candidiasis

Antibody responses to candidal polypeptides and mannans were studied in patients with systemic candidiasis, candiduria, and other fungal and bacterial infections, and in healthy laboratory personnel to determine the diagnostic value of these immunologic responses. When tested by immunoblot analysis, sera from 15 patients with systemic candidiasis frequently contained antibodies to three antigens: 15 of 15 sera from patients with invasive disease reacted to a molecular species having a molecular weight (Mr of 90-200 kd, 13 of 15 reacted with a 45-kd polypeptide, and 12 of 15 reacted with a 17-kd polypeptide. Lesser reactivity was observed in 11 of 15 sera with a 28-kd candidal antigen and in 9 of 15 to a 57-kd candidal antigen. Quantitation of antibody titers against the 45-kd candidal polypeptide demonstrated much higher immunoreactivity in patients with systemic candidiasis than in patients with superficial candidal infections, bacterial infections, other systemic mycoses, and healthy individuals. Antimannan antibody titers were measured by an enzyme-linked immunosorbent assay (ELISA) and these titers were also higher in patients with systemic candidiasis than in patients in the other categories. These differences, however, were less than those observed with the anti-45-kd polypeptide antibody. Therefore, the ability to detect systemic candidiasis is improved by testing sera for immunoreactivity to polypeptide and to mannan antigens from Candida albicans. Detection of polypeptide antibodies improves the serodiagnosis of systemic candidiasis.     

An analysis of community and hospital-acquired bacteraemia in a large teaching hospital in the United Kingdom

A total of 875 episodes of bacteraemia and fungaemia were analysed in patients admitted to University Hospital, Nottingham, and three smaller hospitals over a four-year period. In 814 episodes (93 per cent) a single organism was isolated, most commonly Escherichia coli (27.4 per cent), other enterobacteria (14.4 per cent), Staphylococcus aureus (11.2 per cent), Streptococcus pneumoniae (9.0 per cent), or Haemophilus influenzae (6.4 per cent). In 61 cases (7.0 per cent) bacteraemia was due to two or more species. In almost 60 per cent of cases, bacteraemia was considered to be community-acquired. The most common sources were the urinary (26.9 per cent), respiratory (14.6 per cent), gastrointestinal (11.6 per cent) and biliary (9.5 per cent) tracts, but in almost 10 per cent of cases the focus of infection was unknown. Polymicrobial bacteraemia was common when the biliary tract was the focus of infection. Shock was recorded in 19.5 per cent of cases, and was commoner in polymicrobial (42.9 per cent) than in monomicrobial (17.4 per cent) episodes. In monomicrobial episodes haemolytic streptococci were associated with the highest incidence of shock (30.0 per cent). Mortality directly related to bacteraemia (19.5 per cent) was higher with Gram-positive (23.5 per cent) than with Gram-negative (15.8 per cent) organisms; in polymicrobial (31.1 per cent) than in monomicrobial episodes (18.7 per cent); and in those who had multiple episodes (34.7 per cent) than in those who had a single episode of bacteraemia (20.3 per cent). Other factors influencing mortality included shock, failure to mount an adequate febrile response, leucopenia or granulocytopenia, and underlying disease. Mortality was markedly reduced by appropriate treatment; a single antimicrobial agent was as effective as combination therapy in bacteraemia caused by Gram-negative bacilli.     

Non-albicans Candida is the most common cause of candidemia in pediatric cancer patients

GOALS: Candidemia is a serious infection that can severely complicate the care of children with cancer. We sought to determine the spectrum of Candida species in children with cancer, since effective therapy may depend on the species involved. PATIENTS AND METHODS: A retrospective review of candidemia episodes in our pediatric oncology patients over a 9-year period was conducted. During this period azole prophylaxis was not routine in this group. RESULTS: 38 episodes of candidemia were identified: C. albicans 29%, C. tropicalis 26%, C. parapsilosis 24%, C. krusei 8%, C. glabrata 8%, and C. lusitaniae 5%. Non-albicans Candida was common in patients not receiving azole prophylaxis. Species typically susceptible to azoles were common among patients not using azoles. Death attributed to the fungal infection occurred in 21% of episodes, with nearly all the deaths occurring in patients with C. albicans and C. tropicalis. CONCLUSIONS: C. albicans is not the predominant species in pediatric oncology patients experiencing candidemia, even in azole-naive patients.     

Oral and pharyngeal candidiasis. Topical agents for management and prevention

About half of the general population harbors Candida species in oral flora, and oral candidal infections are common. However, in immunocompromised or immunosuppressed patients, candidiasis may progress to life-threatening systemic disease. Patients with human immunodeficiency virus (HIV), acquired immunodeficiency syndrome, HIV disease, diabetes, or leukemia are particularly prone to serious systemic infection. Chemotherapy for cancer and bone marrow and organ transplantation also provide physiologic opportunities for candidal colonization. Topical therapy has the potential to prevent and treat candidiasis with less risk of side effects and drug interactions than systemic therapy. Among the effective topical agents are polyene antifungal antibiotics and imidazole compounds. Some of these agents have been found useful in prevention of serious candidal infection in high-risk patients; however, more study is needed in this area.     

Nosocomial fungal infections: candidemia.

Candida species are frequently encountered as part of the human commensal flora. Colonization mostly precedes candidemia and is an independent risk factor for the development of candidemia. Genotyping methods showed the similarity between colonizing and infecting strains, thus making endogenous origin likely, though exogenous sources like total parenteral nutrition also have been described. Health care workers (HCWs) play an important role in the transmission of yeasts. Candida species are frequently isolated from the hands of HCWs and can be transmitted from hands to patients. Granulocytopenia and damage of the mucosal lining resulting from intensive chemotherapy due to cancer, the increasing use of broad spectrum antibiotics, and the use of intravenous catheters are other important risk factors for the development of candidemia. Candidemia is associated with a high mortality and prolonged hospitalization. Therefore, and because of the high frequency of dissemination, all candidemias should be treated. Amphotericin B was considered the standard drug for the systemic treatment of candidemia. Fluconazole has been shown to be an effective and safe alternative in non-neutropenic patients. 5-Fluorocytosine has been used in combination with amphotericin B in the treatment of deep-seated infections. Liposomal formulations of amphotericin B and other new antifungal drugs currently are under investigation. C. albicans is the most frequently isolated Candida species, although the proportion of infections caused by non-C. albicans species is increasing. Also, there are reports of development of resistance to amphotericin B. C. lusitaniae is known for primary resistance and the development of resistance to amphotericin B. Development of resistance to fluconazole is mainly seen in AIDS patients with recurrent oropharyngeal candidiasis who receive longer courses of therapy.     

Candidemia due to Candida tropicalis: clinical, epidemiologic, and microbiologic characteristics of 188 episodes occurring in tertiary care hospitals

Candida tropicalis is the 2nd most frequent agent of candidemia in Brazil (20-24%). We attempted to characterize the epidemiology, microbiology, and outcome of candidemia due to C. tropicalis by comparing patients with candidemia due to C. tropicalis with those with candidemia due to Candida albicans. Among the 924 episodes of candidemia, 188 (20%) were caused by C. tropicalis. These cases were compared with 384 candidemias due to C. albicans. C. tropicalis was the 2nd most frequent species in adults (21.6%) and elderly patients (23.2%), and 3rd in neonates (11.9%) and children (18.5%). Cancer was the most frequent underlying disease, and in adults and elderly patients, diabetes was the 2nd most frequent underlying disease. The only difference between C. tropicalis and C. albicans candidemia was a higher proportion of neutropenic patients in C. tropicalis candidemia. C. tropicalis is a leading cause of candidemia in Brazil, and its epidemiology is similar to that of C. albicans.     

Impact of prior inappropriate fluconazole dosing on isolation of fluconazole-nonsusceptible Candida species in hospitalized patients with candidemia

Prior use of fluconazole is a modifiable risk factor for the isolation of fluconazole-nonsusceptible Candida species. Optimization of the use of fluconazole by appropriate dose or duration may be able to minimize the risk of resistance. The objective of this study was to evaluate the effects of prior fluconazole therapy, including the dose and duration, on fluconazole susceptibility among Candida species isolated from hospitalized patients with candidemia. A retrospective cohort study of hospitalized patients with a first occurrence of nosocomial candidemia, from 2006 to 2009, was carried out. The relationships between the initial dose and duration of prior fluconazole therapy and the isolation of fluconazole-nonsusceptible Candida species were assessed. An initial fluconazole dose greater than 2 mg/kg and less than 6 mg/kg of body weight was considered suboptimal. A total of 177 patients were identified, of whom 133 patients aged 61 ± 16 years (56% male, 51% Caucasian, 51% with an APACHE II score of ≥ 15) had candidemia more than 2 days after the hospital admission day. Nine of 107 (8%) patients with fluconazole-susceptible Candida species and 9 of 26 (35%) patients with fluconazole-nonsusceptible Candida species had prior fluconazole exposure (risk ratio [RR], 3.03; 95% confidence interval [95% CI], 1.57 to 5.86; P, 0.0022). Preexposure with an initial dose of fluconazole greater than 2 mg/kg and less than 6 mg/kg occurred in 3 of 9 (33%) and 8 of 9 (89%) patients with fluconazole-susceptible and fluconazole-nonsusceptible Candida species, respectively (P, 0.0498). We conclude that patients with candidemia due to fluconazole-nonsusceptible Candida species were more likely to have received prior fluconazole therapy. Suboptimal initial dosing of prior fluconazole therapy was associated with candidemia with fluconazole-nonsusceptible Candida species.     

不同免疫状态患者念珠菌血症的实验室检测特征分析

目的探讨不同免疫状态患者念珠菌血症的病原菌分布及药敏、血清标志物等实验室检验指标的差异。方法回顾性收集分析2016年1月-2018年12月重庆医科大学附属第一医院念珠菌血症患者的临床和实验室相关资料。结果103例患者纳入分析,免疫抑制组58例,非免疫抑制组45例。非免疫抑制组接受体内导管置入和完全肠外营养的比例明显高于免疫抑制组;微生物学特征显示免疫抑制组的热带念珠菌分离率明显高于非免疫抑制组,非免疫抑制组的近平滑念珠菌分离率明显高于免疫抑制组;对三唑类抗真菌药物的整体敏感率免疫抑制组低于非免疫抑制组,耐药菌主要为热带念珠菌;发生念珠菌血症时,两组患者血清降钙素原和C反应蛋白值均高于参考值范围;免疫抑制组患者血清(1,3)-β-D葡聚糖(BDG)阴性率明显高于非免疫抑制组。结论根据患者不同免疫状态,更好识别不同患者的病原菌分布特点,有助于临床医师选择更合理的抗真菌药物。然而,血清BDG检测不能早期识别所有念珠菌血症患者,特别是免疫抑制患者,需要结合降钙素原和C反应蛋白值综合判断。