Application of prone position in severe ARDS caused by pneumocystis jirovecii pneumonia after kidney transplantation / 器官移植

Objective To investigate the improvement of oxygenation after the treatment of prone position in patients with severe acute respiratory distress syndrome (ARDS) caused by pneumocystis jirovecii pneumonia (PJP) after kidney transplantation. Methods Clinical data of 5 cases of moderate and severe ARDS caused by PJP after kidney transplantation were analyzed retrospectively, and clinical characteristics, treatment regimen and prognosis were summarized. Results Clinical manifestations of 5 patients were fever, dry cough, chest tightness, shortness ofbreath,sweating and fatigue, and body temperature fluctuated between 38 ℃ and 39 ℃, percutaneous arterial oxygen saturation(SpO2) was gradually decreased, and respiratory distress symptoms were worsened. Pulmonary CT scan showed diffuse ground-glass shadow. After transfer to intensive care unit (ICU), immunosuppressive drugs were terminated, and all patients were given with compound sulfamethoxazole, caspofungin, low-dose glucocorticoids against pneumocystis jirovecii (PJ), oxygen therapy and other symptomatic supportive treatments. Four patients diagnosed with severe ARDS upon admission to ICU were treated in a prone position. One patient with moderate ARDS was not kept in a prone position. At 1 d after treatment in a prone position, partial pressure of arterial oxygen (PaO2) and oxygenation index were increased, whereas alveolar-arterial oxygen difference (A-aDO2) was decreased compared with before treatment (allP<0.05). Compared with 1 d after treatment, SpO2, PaO2 and oxygenation index were all increased, while A-aDO2 was decreased at 4 d after treatment (all P<0.05). Box diagram showed that oxygenation index showed an overall upward trend after prone-position treatment, whereas A-aDO2 showed an overall downward trend. The length of ICU stay of 5 patients was 14 (8, 29) d. All patients in a prone position did not develop complications, such as skin pressure sore, tube detachment and tube displacement, etc. Among 5 patients, 4 patients were mitigated, and 1 patient died of septic shock and multiple organ failure. Conclusions For both conscious and intubated patients, a prone position may significantly improve oxygenation and prognosis of patients with severe ARDS caused by PJP after kidney transplantation. Early diagnosis and accurate and standardized treatment play a pivotal role in enhancing cure rate.

Efficacy and safety of trimethoprim/sulfamethoxazole combined with caspofungin for the treatment of acquired immunodeficiency syndrome patients with moderate to severe pneumocystis pneumonia / 中华传染病杂志

Objective:To assess the efficacy and safety of trimethoprim/sulfamethoxazole (TMP/SMZ) combined with caspofungin for the treatment of acquired immunodeficiency syndrome (AIDS)patients with moderate to severe pneumocystis pneumonia (PCP) requiring mechanical ventilation.Methods:The clinical data of AIDS patients who admitted to Chongqing Public Health Medical Center from March 1, 2019 to March 1, 2021 with moderate to severe PCP requiring mechanical ventilation were retrospectively analyzed. Clinical characteristics and outcomes were compared between two groups receiving either combination therapy with TMP/SMZ and caspofungin (combination therapy group) or TMP/SMZ monotherapy (monotherapy group). The patients were divided into two subgroups according to the baseline arterial partial pressure of oxygen (PaO 2), patients with arterial PaO 2≥50 mmHg (1 mmHg=0.133 kPa) and PaO 2 <50 mmHg. The clinical efficacies of combination therapy and monotherapy in each subgroup were further compared. Chi-square and Fisher exact test were used for statistical analysis. The three-month survival was estimated by the Kaplan-Meier method, and the three-month survival rates were compared by Log-rank method. Results:A total of 83 patients were enrolled, including 23 in the monotherapy group and 60 in the combination therapy group. There was no significant difference in all-cause hospital mortalities between these two groups (34.8%(8/23) vs 23.3%(14/60), χ2=1.12, P=0.290). Kaplan-Meier survival curves indicated no significant difference in the three-month survival rates between the two groups ( χ2=0.51, P=0.477). There ware no significant differences observed in the positive clinical response rates and the mechanical ventilation rates after seven days of anti-PCP treatment between the two groups ( χ2=0.02 and 0.01, respectively, both P>0.05). In the 52 patients with PaO 2≥50 mmHg, no significant difference in all-cause hospital mortalities was observed between the monotherapy group and the combination therapy group (2/13 vs 25.6%(10/39), χ2=0.14, P=0.704). There was no statistical significance in the three-month survival rates between the two groups ( χ2=0.69, P=0.407). No significant difference was observed either in the clinical positive response rates or the mechanical ventilation rates after seven days of anti-PCP treatment between the two group( χ2=1.02 and 0.69, respectively, both P>0.05). In the 31 patients with PaO 2<50 mmHg, the all-cause hospital mortality in the combination therapy group was 19.0%(4/21), while six of the 10 patients in the monotherapy group died, and the difference was statistically significant (Fisher exact test, P=0.040). The three-month survival rate in the combination therapy group was significantly higher than that in the monotherapy group ( χ2=4.09, P=0.043). There were no significant differences in clinical positive response rate and the mechanical ventilation rate after seven days of anti-PCP treatment between the two group (Fisher exact test, both P>0.05). The overall adverse event rate in the monotherapy group was 87.0%(20/23), with an incidence of 56.5%(13/23) for both electrolyte disturbances and bone marrow suppression. The above incidences in the combination therapy group were 78.3%(47/60), 35.0%(21/60) and 53.3%(32/60), respectively, and all differences were not statistically significant ( χ2=0.34, 3.18 and 0.07, respectively, all P>0.05). Conclusions:The efficacy of combination therapy with TMP/SMZ and caspofungin is comparable to that of TMP/SMZ monotherapy in AIDS patients with moderate to severe PCP requiring mechanical ventilation. However, in AIDS patients with PCP requiring mechanical ventilation with the baseline PaO 2<50 mmHg, the efficacy of combination therapy is statistically superior to that of TMP/SMZ monotherapy. Combination therapy does not increase the risk of adverse events.

Advances in population pharmacokinetics-pharmacodynamics of caspofungin / 中国药房

Caspofungin is the firs t echinocandin antifungal drug approved for serious fungal infections caused by Candida or Aspergillus. Currently ，caspofungin has been recommended as the first-line treatment for invasive Candida and the second-line treatment for invasive Aspergillus，for its safety and tolerability. However ，there are still probability of pharmacokinetic variability and the risk of low exposure in different populations. Herein the population pharmacokinetics-pharmacodynamics studies of caspofungin in children and adults were reviewed. The results indicate that the body surface area was the main factor affecting the distribution and clearance of caspofungin in pediatric patients. In adults ，the two-compartment model fits the caspofungin behavior best in vivo with the primary covariates of body weight and albumin level. The efficacy of caspofungin might be related to pharmacokinetics-pharmacodynamics parameters ，such as the ratio of area under blood concentration time curve to minimum inhibitory concentration （AUC/MIC），the ratio of peak concentration to minimum effective concentration （cmax/MEC）.

Consensus statement on the management of invasive candidiasis in Indian scenario

Invasive fungal infections in critically ill patients are associated with increased morbidity and mortality. Candida species are among the most common causes of nosocomial bloodstream infections and of invasive infections in intensive care units (ICUs). The high mortality mandates early identification of invasive candidiasis which is vital to initiate appropriate and timely treatment and improve outcomes. Delaying the initiation of treatment could result in an increase in mortality which can be avoided by usage of more rapid diagnostic techniques. There are multiple diagnostic tests including culture and non-culture tests like 1,3-β-D-glucan and newer techniques like MALDI-TOF which are available to diagnose candidemia but each with their drawbacks. Additionally, there are various guidelines like IDSA and ESCMID on treatment which aim to minimize death, late complications from deep-seated candidiasis and rise of drug- resistant Candida strains. Through this consensus statement prepared by a panel of experts, all of whom are senior intensivists, infectious disease specialists and microbiologists, we aim to address the major aspects of management of invasive candidiasis in the Indian population as per the authors opinions, backed by published evidence and supported by the latest clinical guidelines.

Efficacy and safety of high-dose caspofungin in the treatment of invasive pulmonary aspergillosis / 中华传染病杂志

Objective To investigate the clinical efficacy and safety of high-dose caspofungin (70 mg/d)as initial or salvage treatment for invasive pulmonary aspergillosis.Methods Twenty-one patients with proven or probable invasive pulmonary aspergillosis from June 2014 to October 2017 in Huashan Hospital,Fudan University were retrospectively reviewed.According to the anti-fungal treatment before high-dose caspofungin application,patients were divided into initial treatment group and salvage treatment group.Patients' clinical data and laboratory data were collected.The characteristics,clinical efficacy,adverse reactions,one-year survival rate and the overall effective rate were evaluated.The prognosis of the two groups was compared by Kaplan-Meier analysis.Results Twenty of the 21 patients opportunistic acquired invasive pulmonary aspergillosis during the treatment of underlying diseases.Five patients were initially treated with high-dose caspofungin for 68 (62) days.At week 12,one patient achieved complete response,3 patients achieved partial response,and the overall effective rate was 80％ (4/5).Sixteen patients received caspofungin as salvage therapy for 66.50 (58) days,of which one patient got complete response at week 12,10 had partial response,and the overall effective rate was 68.75％ (11/16).One-year follow-up showed that no patient died in the initial treatment group,and the one-year survival rate was 100％ (5/5).In salvage treatment group,3 patients died of pulmonary bacterial infections and the one-year survival rate was 81.25％ (13/16).During treatment,one patient had elevated total bilirubin,which was possibly associated with high-dose caspofungin.Conclusions High-dose caspofungin regimen has good efficacy and safety,both for initial treatment and salvage therapy in patients with invasive pulmonary aspergillosis.

Echinocandins: Their role in the management of Candida biofilms

The importance of antifungal agents and their clinical implications has received little attention in comparison to antibiotics, particularly in the health-care setting. However, apart from bacterial infections rising in hospitals, the incidences of fungal infections are growing with the development of resistance to conventional antifungal agents. Newer antifungal agents such as echinocandins (ECs) have been extensively studied over the past decade and are recognised as a superior treatment compared with prior antifungals as a first line of therapy in tertiary institutions. Caspofungin (CAS), micafungin (MICA) and anidulafungin (ANID) are the three most widely used EC antifungal agents. The treatment of biofilm-associated fungal infections affecting patients in tertiary health-care facilities has been identified as a challenge, particularly in Indian Intensive Care Unit (ICU) settings. With the rising number of critically ill patients requiring invasive devices such as central venous catheters for treatment, especially in ICUs, these devices serve as a potential source of nosocomial infections. Candida spp. colonisation is a major precursor of these infections and further complicates and prolongs treatment procedures, adding to increasing costs both for hospitals and the patient. Analysing studies involving the use of these agents can help in making critical decisions for antifungal therapy in the event of a fungal infection in the ICU. In addition, the development of resistance to antifungal agents is a crucial factor for assessing the appropriate antifungals that can be used for treatment. This review provides an overview of ANID in biofilms, along with CAS and MICA, in terms of clinical efficacy, resistance development and potency, primarily against Candida spp.

In vitro antifungal activity of four antifungal agents alone or in combination against Exophiala dermatitidis biofilms / 中华皮肤科杂志

Objective To evaluate the in vitro antifungal activity of 4 antifungal agents alone or in combination against Exophiala dermatitidis (E.dermatitidis) biofilms.Methods E.dermatitidis biofilms were prepared by using a modified 96-well plate-based method.The in vitro antifungal activity of amphotericin B,voriconazole,itraconazole and caspofungin alone or in combination against E.dermatitidis biofilms were investigated via the broth microdilution checkerboard technique.Results The sessile minimum inhibitory concentration ranges resulting in 50％ (SMICS0) and 80％ inhibition (SMIC80) of E.dermatitidis biofilms were all ＞ 32 mg/L for itraconazole,voriconazole and caspofungin,and the SMIC50 and SMIC80 ranges of amphotericin B were 1-2 mg/L and 4-8 mg/L respectively.The combination of amphotericin B with voriconazole showed synergistic inhibitory effects against E.dermatitidis biofilms,while the combination of amphotericin B with itraconazole or caspofungin,as well as the combination of voriconazole with caspofungin,revealed no synergistic effects.No antagonistic effect was observed in any of the combinations.Conclusion Amphotericin B appears more active against E.dermatitidis biofilms,and the combination with voriconazole can enhance the anti-biofilm effects against E.dermatitidis biofilms.

Activador tisular del plasminógeno recombinante para el tratamiento de la vegetación intracardíaca en un lactante de muy bajo peso al nacer / Recombinant tissue plasminogen activator treatment for intracardiac vegetation in a very low birth weight infant

Las nuevas opciones de tratamiento prolongan la hospitalización y aumentan las infecciones intrahospitalarias bacterianas y fúngicas, pero también mejoran la sobrevida de los recién nacidos hospitalizados en la unidad de cuidados intensivos neonatales. Las infecciones fúngicas invasivas en neonatos están asociadas con una morbimortalidad significativa. También pueden diseminarse a órganos específicos y causar endocarditis, endoftalmitis, artritis séptica, nefropatía obstructiva y meningitis. En el caso de la endocarditis, se recomiendan tratamientos antimicóticos sistémicos agresivos y, en algunos casos, la intervención quirúrgica del neonato. Informamos el caso de un lactante prematuro, de bajo peso al nacer, con vegetación intracardíaca. Esta es una complicación rara y potencialmente mortal de infecciones fúngicas invasivas. El paciente recibió tratamiento con caspofungina y un activador tisular del plasminógeno recombinante, en vez de una intervención quirúrgica.

Developing treatment options have resulted in prolonged admission and increased bacterial and fungal nosocomial infections as well as improved survival in neonatal intensive care unit. Invasive fungal infections in newborns are associated with significant morbidity and mortality and can cause endorgan dissemination such as endocarditis, endophthalmitis, septic arthritis, obstructive nephropathy and meningitis. Endocarditis requires aggressive systemic antifungal therapy and sometimes surgical intervention in neonates. We report a low birth weight premature infant with intracardiac vegetation that is rare and a life-threatening complication of invasive fungal infections. He was treated with caspofungin and recombinant tissue plasminogen activator in stead of surgical intervention.

Antifungal activity of caspofungin in experimental infective endocarditis caused by Candida albicans

BACKGROUND Infective endocarditis is a disease characterised by heart valve lesions, which exhibit extracellular matrix proteins that act as a physical barrier to prevent the passage of antimicrobial agents. The genus Candida has acquired clinical importance given that it is increasingly being isolated from cases of nosocomial infections. OBJECTIVE To evaluate the activity of caspofungin compared to that of liposomal amphotericin B against Candida albicans in experimental infective endocarditis. METHODS Wistar rats underwent surgical intervention and infection with strains of C. albicans to develop infective endocarditis. Three groups were formed: the first group was treated with caspofungin, the second with liposomal amphotericin B, and the third received a placebo. In vitro sensitivity was first determined to further evaluate the effect of these treatments on a rat experimental model of endocarditis by semiquantitative culture of fibrinous vegetations and histological analysis. FINDINGS Our semiquantitative culture of growing vegetation showed massive C. albicans colonisation in rats without treatment, whereas rats treated with caspofungin showed significantly reduced colonisation, which was similar to the results obtained with liposomal amphotericin B. CONCLUSIONS The antifungal activity of caspofungin is similar to that of liposomal amphotericin B in an experimental model of infective endocarditis caused by C. albicans.

Economic Evaluation of Caspofungin vs. Voriconazole in Initial Empirical Antifungal Therapy of Febrile Neutropenia / 中国药房

OBJECTIVE:To evaluate the economics of caspofungin vs. voriconazole in initial empirical antifungal therapy of fe-brile neutropenia(FN). METHODS:Based on two international multiple center clinical trials about caspofungin vs. voriconazole in initial empirical antifungal therapy of FN,combined with domestic clinical experts'opinions about drug selection,a decision tree model was developed. TreeAge Pro 2011 software was used to analyze the cost and effectiveness of 10-day therapy of caspofungin or voriconazole as initial empirical antifungal therapy. RESULTS:The direct medical cost of caspofungin group was lower than that of voriconazole group(52826.71 yuan vs. 58246.70 yuan). The success rate and survival rate were higher than voriconazole group(33.95% vs. 25.63%、92.36% vs. 91.87%). Whether the success rate or the survival rate of patients as the effect indicators, cost-effectiveness ratio of caspofungin group was lower than that of voriconazole group. Moreover,incremental cost effectiveness ra-tio and sensitivity analysis confirmed this conclusion. CONCLUSIONS:Caspofungin has more advantages than voriconazole in cost and effectiveness as initial empirical antifungal therapy in patients with FN.

Voriconazole plus caspofungin for treatment of invasive fungal infection in children with acute leukemia

BACKGROUND: Invasive fungal infections (IFIs) are a life-threatening problem in immunocompromised patients. Despite timely diagnosis and appropriate antifungal therapy, clinical outcomes of IFIs remain unsatisfactory, necessitating treatment with a combination of antifungal agents. Therefore, childhood leukemic patients treated with voriconazole plus caspofungin were evaluated for the safety and efficacy of the combination antifungal therapy to treat IFIs. METHODS: In this retrospective study, medical records were retrieved for patients admitted to the Pediatric Department of Yeungnam University Hospital, Daegu, South Korea, between April 2009 and May 2013. Medical records of 22 patients were analyzed. RESULTS: Of the 22 patients studied, nine (41%) had been diagnosed with probable IFI, and 13 (59%) with possible IFI. All patients, except one, were already receiving antifungal monotherapy for the treatment of neutropenic fever. After a diagnosis of IFI was confirmed, antifungal monotherapy was replaced with combination therapy. The study's overall response rate was 90.9%, with complete responses in 86.3% of the patients. Two patients experienced a side effect of a small increase in liver enzyme levels. CONCLUSION: Voriconazole plus caspofungin combination therapy is an effective and safe treatment for serious IFI in pediatric patients with acute leukemia.

Eficacia y seguridad de la caspofungina en pediatría: revisión sistemática y metaanálisis / Efficacy and safety of caspofungin in children: systematic review and meta-analysis

Las infecciones fúngicas invasivas son una importante causa de morbimortalidad en pediatría. La caspofungina es una equinocandina utilizada como alternativa en la prevención y/o tratamiento de ciertas infecciones fúngicas invasivas en niños, aunque con poca evidencia sobre su eficacia y seguridad en comparación con el tratamiento habitual. Objetivos. Evaluar la eficacia y seguridad de la caspofungina comparada con otros antifúngicos en la prevención y/o tratamiento de infecciones fúngicas invasivas en pediatría. Material y métodos. La estrategia de búsqueda inicial tuvo como objetivo identificar estudios controlados aleatorizados de aceptable calidad metodológica (escala de Jadad > 3) mediante la palabra clave "caspofungin" realizados en pacientes de entre los 0 y los 18 años. Resultados. Solo 3 publicaciones cumplieron los criterios de inclusión. De ellas, 2 fueron en población pediátrica y una en neonatal. No se documentó una mayor incidencia de efectos adversos para la caspofungina y su eficacia no se diferenció de otros antifúngicos (RR típico 1,47; IC 95%: 0,78-2,79). Conclusiones. Esta revisión sistemática sugiere que la caspofungina podría considerarse como una alternativa para su indicación en pediatría en la prevención y tratamiento de las infecciones fúngicas invasivas. Sin embargo, dado el pequeño número de publicaciones existentes, se requieren más estudios para alcanzar conclusiones definitivas.

Invasive fungal infections are a significant cause of morbidity and mortality in children. Caspofungin is an echinocandin used as an alternative treatment in the prevention and/or treatment of certain invasive fungal infections in children, although compared to the standard treatment there is little evidence on its efficacy and safety. Objectives. To evaluate the efficacy and safety of caspofungin compared with other antifungal drugs for the prevention and/or treatment of invasive fungal infections in children. Material and methods. The objective of the initial search strategy was to identify randomized controlled studies of acceptable methodological quality (Jadad scale >3), through the key word "caspofungin", conducted in patients with an age range from 0 to 18 years old. Results. Only 3 publications met the inclusion criteria. Two of them were studies conducted in children and one in newborn infants. A higher incidence of adverse events was not documented for caspofungin and its efficacy was not different from that of other antifungal drugs (typical RR 1.47; CI 95%: 0.78-2.79). Conclusions. This systematic review suggests that caspofungin could be considered as an alternative drug in children for the prevention and treatment of invasive fungal infections. However, given the small number of existing publications, more studies are required to reach definite conclusions.

Clinical Observation of Caspofungin Acetate in the Treatment of Invasive Pulmoary Fungal Infection / 中国药房

OBJECTIVE:To observe the clinical efficacy and safety of caspofungin acetate in the treatment of invasive pulmo-nary fungal infection(IPFI). METHODS:70 patients with IPFI were selected and randomly divided into observation group(40 cas-es) and control group (30 cases). Control group was given Itraconazole injection with initial dose of 250 mg,bid,decreasing to 200 mg,qd,2 days later;observation group was given Caspofungin acetate injection 70 mg on the first day,decreasing to 50 mg, ivgtt,qd,within 1 h. Clinical efficacy,the rate of nacterial smear negative conversion and ADR were observed in 2 groups. RE-SULTS:The total effective rate of observation group was 92.50%,which was significantly higher than that of control group (76.67%);the rate of nacterial smear negative conversion was 72.00% in observation group,which was significantly higher than that of control group(42.10%);the incidence of ADR was 7.50%in observation group,which was significantly lower than that of control group (13.33%),with statistical significance (P<0.05). CONCLUSIONS:Caspofungin acetate is effective for IPFI with low incidence of ADR.

The efficacy and safety of caspofungin in the treatment of patients with acute exacerbation of chronic obstructive pulmonary disease and pulmonary fungal infections / 中国基层医药

Objective To study and analyze the efficacy and safety of caspofungin in the treatment of acute exacerbation of chronic obstructive pulmonary disease patients complicated with pulmonary fungal infections.Methods 62 patients of acute exacerbation of chronic obstructive pulmonary disease complicated with pulmonary fungal infec-tions were randomly divided into study group and control group,31 cases in each group.Study group was intravenously given caspofungin,with an initial dose of 70mg/d,follow 50mg/d.The control group was intravenously given liposomal amphotericin B,dose control in 3mg? kg-1 ? d-1 .After treatment lasted symptoms 5d,clinical efficacy and side effects of two groups were recorded.Results The effective rate of the study group was 67.74%,which was signifi-cantly higher than 41.93% of the control group, the difference was statistically significant ( χ2 =2.0251, P =0.0429).The incidence rate of adverse reactions of the study group was 16.13%,which was significantly lower than 48.39% of the control group,the difference was statistically significant(χ2 =2.6948,P =0.0070).After treatment, liver and kidney function parameters in the control group such as ALT,AST,BUN,Cr had significant differences com-pared with before treatment (P <0.05).Conclusion For chronic obstructive pulmonary disease patients complicated with acute exacerbation of pulmonary fungal infection,the treatment efficacy and the incidence of adverse reactions of caspofungin therapy are significantly better than liposomal amphotericin B,and has small renal damage,which is wor-thy of clinical application.

Practice of Clinical Pharmacists Participating in Anti-infective Treatment for A Patient with Tropical Candi-demia / 中国药房

OBJECTIVE:To explore the role of clinical pharmacists participating in drug therapy for patients with severe infec-tions. METHODS:Clinical pharmacists participated in drug treatment for a patient with tropical candidemia and assisted physicians to adjust anti-infective treatment plan. According to the results of blood culture,clinical pharmacists suggested Piperacillin sodium and tazobactam sodium for injection 3.75 g,ivgtt,q8 h+Caspofungin acetate for injection 50 mg (initial dose of 70 mg),ivgtt, qd,for symptomatic treatment;increased the daily dose of Caspofungin acetate for injection to 50 mg,ivgtt,bid due to plasma ex-change;Caspofungin acetate for injection 50 mg,ivgtt,qd+Amphotericin B for injection 0.1 mg/kg,ivgtt,qd for anti-infective plan due to the possible“contradiction”of echinocandins;closely monitored ADR,such as allergy,erythra,renal function injury. RE-SULTS:Physicians adopted the suggestions of clinical pharmacists,vital sign of patient kept stable,and tropical candidemia was not detected in the blood culture;the patient was transferred to general ward for further treatment. CONCLUSIONS:Based on the results of blood calture,clinical symptoms and the characteristics of drug effects,clinical pharmacists participated in the treatment for the patient with severe infection,retrieved related treatment guideline,assisted physicians to adjust anti-infective plan and close-ly monitored possible ADR so as to guarantee the effectiveness and safety of anti-infective treatment.

A non-controlled, multicenter open-label study to evaluate the safety, tolerability and efficacy of caspofungin in the treatment of invasive candidiasis and esophageal candidiasis / 中国感染与化疗杂志

Objective This study was designed to evaluate the safety ,tolerability and efficacy of intravenous caspofungin for treatment of invasive candidiasis and esophageal candidiasis in Chinese adults .Methods This was a non-controlled ,multicenter ,candidiasis .All the 63 patients were included in the safety set (SS) and the full analysis set (FAS) .In the SS ,19 SAEs occurred in 14 patients .All these SAEs were unrelated to caspofungin .There were 73 caspofungin-related non-serious AEs in 31 patients (49 .2% ) .Five patients (7 .9% ) had both clinical AEs and laboratory abnormalities .Eight patients (12 .7% ) had clinical AEs (mainly rashes) ,and 27 patients (42 .9% ) had laboratory abnormalities ,mainly increases in liver enzymes alanine transaminase and aspartate transaminase and reduction in blood potassium .About 91 .7% of the clinical AEs were mild to moderate .Treatment was discontinued in 1 patient (1 .6% ,1/63) due to AEs .The overall efficacy was 58 .1% (36/62) in the FAS and 70 .0% (35/70) in the per-protocol set (PPS) .In the FAS ,the therapeutic efficacy was 57 .6% (34/59) for invasive candidiasis and 66 .7% (2/3) for esophageal candidiasis .In the PPS , the therapeutic efficacy was 68 .8% (33/48 ) for invasive candidiasis and 100% (3/3 ) for esophageal candidiasis .Conclusions The AEs of caspofungin were mostly mild to moderate in the treatment of invasive candidiasis and esophageal candidiasis in Chinese adults .Only one patient terminated therapy due to drug-related AE .Caspofungin is safe and effective for the treatment of invasive candidiasis and esophageal candidiasis in Chinese adults .

Profilaxis antifúngica en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos / Prophylaxis against fungal infections in solid organ and hematopoietic stem cells transplantation

Invasive fungal infections are an important cause of morbidity and mortality in SOT and HSCT recipients. The main species involved are Candida spp. and Aspergillus spp, less frequently Cryptococcus spp., causal agents of mucormycosis and Fusarium spp. Usually occur within the first six months post-transplant, but they do it later, especially during episodes of rejection, which maintains the state of immune system involvement. Prophylaxis recommendations are specific to each type of transplant. In liver transplantation use of fluconazole is recommended only in selected cases by high risk factor for invasive fungal infections (A1). If the patient has a high risk of aspergillosis, there are some suggestions for adults population to use amphotericin B-deoxycholate, liposomal amphotericin B or caspofungin (C2) without being validated none of these recommendations in pediatric population. In adult lung transplant patients where the risk of aspergillosis is higher than in other locations, we recommend universal prophylaxis with itraconazole 200 mg/day, nebulised liposomal amphotericin B or voriconazole (C2), no validated recommendations for pediatrics. In HSCT, universal prophylaxis is recommended only in allogeneic and autologous selected cases. The most accepted indication is fluconazole (A1), and posaconazole (A1) or micafungin (A1) in selected cases with high risk of aspergillosis.

Las infecciones fúngicas invasoras constituyen una importante causa de morbilidad y mortalidad en los pacientes receptores de TOS y TPH. Los principales agentes involucrados son Candida spp. y Aspergillus spp, menos frecuentemente Cryptococcus spp., agentes causales de mucormicosis y Fusarium spp. Se presentan habitualmente dentro de los primeros seis meses posttrasplante, pero también lo hacen en forma más tardía, especialmente durante episodios de rechazo, en que se mantiene el estado de compromiso del sistema inmune. Existen recomendaciones de proilaxis especíicas para cada tipo de trasplante. En trasplante hepático se recomienda el uso de fluconazol sólo en casos seleccionados por factores de riesgo (A1). Si existe riesgo de asper-gilosis, hay algunas sugerencias en adultos para el uso de anfotericina B-deoxicolato, anfotericina liposomal o caspofungina (todo en categoría C2), sin estar validada ninguna de estas recomendaciones en pediatría. En trasplante pulmonar en paciente adulto, donde el riesgo de aspergilosis es superior a otras localizaciones, se recomienda proilaxis universal, con itraconazol 200 mg/día, anfotericina liposomal nebulizada o voriconazol (C2), sin recomendaciones validadas para pediatría. En TPH, se recomienda proilaxis universal en trasplante alogénico y sólo para casos seleccionados en trasplantes autólogos. La indicación más aceptada es fluconazol (A1), siendo alternativas a evaluar dependiendo del riesgo de aspergilosis, posaconazol (A1) y micafungina (A1).

Isolation and antifungal susceptibility testing of Trichosporon asahii in Ceará, Brazil / Isolamento e teste de susceptibilidade aos antifúngicos de Trichosporon asahii no Ceará, Brasil

Trichosporon spp. are yeasts capable of causing invasive disease, which mainly affect immunocompromised patients. A clinical strain of T. asahii was isolated from the blood cultures of patients admitted to the General Hospital of Fortaleza. Susceptibility tests were conducted by disk diffusion and broth microdilution. The isolated strain of T. asahii was resistant to fluconazole. The patient used amphotericin B and caspofungin in order to facilitate the microbiological cure. It was the first isolation and identification of T. asahii in blood culture in Ceará, Brazil.

Trichosporon spp. são leveduras capazes de causar doença invasiva, que afetam principalmente pacientes imunocomprometidos. Uma cepa clínica de T. asahii foi isolada em hemocultura de paciente internado no Hospital Geral de Fortaleza. Os testes de suscetibilidade foram realizados por difusão em disco e microdiluição em caldo. A cepa isolada do T. asahii foi resistente ao fluconazol, o paciente fez uso de anfotericina B e caspofungina então a cura microbiológica ocorreu. Foi o primeiro isolamento e identificação de T. asahii em hemocultura no Ceará, Brasil.

Are Systemic Voriconazole and Caspofungin Ototoxic? An Experimental Study with Rats

OBJECTIVES: To determine whether systemic administration of voriconazole and caspofungin causes ototoxicity. METHODS: This study was conducted on 32 healthy male Wistar albino rats. The baseline auditory brainstem response (ABR) thresholds of all animals were obtained under general anesthesia. Then, the rats were randomly divided into 4 groups (groups I-IV), each group consisting of 8 rats. Rats in group I were injected intraperitoneally with voriconazole 10 mg/kg/day for 7 days, and the rats in the group II were injected intraperitoneally with caspofungin 5 mg/kg/day for 7 days. Group III received 120 mg/kg/day gentamicin for 7 days. Group IV received saline for 7 days. The animals were then observed for 7 days, and on 14th day of the trial, posttreatment ABRs of both ears were recorded. RESULTS: We did not find any significant differences between pretreatment and posttreatment median ABR thresholds in the voriconazole, caspofungin, or saline groups. In the gentamicin group, there was a statistically significant difference between pretreatment and posttreatment ABR thresholds. CONCLUSION: Caspofungin and voriconazole did not change ABR thresholds in speech frequencies after a 7-day-period of their administration. We believe that further animal studies must be performed after administration of these agents for a longer time period, and these findings must be consolidated with histopathological investigations.

Catheter-related Candidemia Caused by Candida haemulonii in a Patient in Long-term Hospital Care

Candida haemulonii, one of the non-albicans Candida species, is an emerging yeast pathogen that is known to be resistant to amphotericin B and other antifungal agents such as azoles. These anti-fungal agents have often been associated with clinical treatment failure, so no treatment regimen has been clearly established for invasive C. haemulonii infections. We investigated a catheter-related infection of C. haemulonii candidemia in an adult patient in long-term hospital care. In the early stages, the candidemia remained persistent despite treatment with fluconazole. However, after changing the antifungal agent to caspofungin, the candidemia was resolved. Fluconazole and amphotericin B are not reliable empirical antifungal agents for invasive C. haemulonii infections, as shown in previous case reports. An echinocandin such as caspofungin may be an appropriate empirical choice of antifungal agent for an invasive C. haemulonii infection.