艾滋病相关卡氏肺孢子菌肺炎的诊断进展

正卡氏肺孢子菌肺炎(PCP)是由卡氏肺孢子菌引起的一种非典型肺炎,是艾滋病患者最为常见的机会性感染~([1])。过去卡氏肺孢子菌被归为原生生物,但是目前认为卡氏肺孢子菌属于真菌,科学家将其更名为jirovecii肺孢子菌,但是为了避免混淆,其缩写仍然沿用"PCP"~([2])。有研究表明,超过一半的免疫力正常的成人会再次感染卡氏肺孢子虫,但是绝大多数并不会     

艾滋病合并重症卡氏肺孢子菌肺炎患者的生存分析

目的 探讨医院住院艾滋病患者合并重症卡氏肺孢子菌肺炎(pneumocystis carinii pneumonia,PCP)的生存时间,为临床治疗时机及选用药物提供参考依据。 方法 对宁波市第二医院2007年3月至2012年6月收治的30例艾滋病合并重症PCP病例进行回顾性分析。将患者CD4+细胞计数及治疗方法采取分层的方法进行生存时间分析,绘制Kaplan-meier曲线,治疗随访时间为30 d。 结果 30例艾滋病合并重症PCP患者共死亡25例,存活5例,其中复方磺胺甲恶唑(TMP-SMZ)治疗16例,患者死亡14例,病死率为87.5%;TMP-SMZ联合强的松治疗14例,患者死亡11例,病死率为78.57%。按CD4+细胞计数分层,TMP-SMZ联合强的松治疗患者累计生存率明显高于单纯TMP-SMZ治疗组;按抗PCP治疗方法分层,CD4+细胞计数4+细胞>50个/μl患者。 结论 艾滋病合并重症PCP患者病死率高,应早发现、早诊断、早治疗。TMP-SMZ联合强的松治疗方案较单纯TMP-SMZ治疗效果更好。     

卡氏肺孢子菌肺炎二例报道及文献复习

卡氏肺孢子虫(pneumocystis carinii,PC)是一种机会感染性真菌,在使用免疫抑制剂患者及艾滋病等免疫缺陷患者,卡氏肺孢子虫所致的卡氏肺孢子菌肺炎(pneumocystis carinii pneumoni-a,PCP)是最常见的感染和致死原因之一[1].卡氏肺孢子虫黏附于肺泡I型上皮细胞而进行繁殖,损失上皮细胞,暴露基底膜[2],所致的肺泡炎是PCP重要的病理改变[3].我们介绍2例PCP患者的临床、胸部影像学及病理资料,并复习文献,以提高对PCP的认识.     

卡氏肺孢子菌肺炎的1例报告

卡氏肺孢子菌肺炎(pneumocystis carinii pneumonia,PCP)是由卡氏肺孢子菌感染引起的呼吸系统机会感染,最初常见于早产儿、器官移植及肿瘤、免疫缺陷的患者.PCP是AIDS患者最常见的机会感染和最主要的致死原因.近年来,由于免疫抑制剂广泛、长期、大剂量应用,恶性肿瘤放化疗以及器官移植患者数量增加迅速,本病发病率有所升高,PCP病情进展迅速,致死率极高,临床上应提高对其的警惕和认识.     

用双氢青蒿素防治卡氏肺孢子虫肺炎的实验研究

目的观察双氢青蒿素防治大鼠卡氏肺孢子虫肺炎(PCP)的效果.方法经皮下注射醋酸可的松诱导大鼠发生PCP.将受试大鼠随机分为实验组和对照组,双氢青蒿素防治方案分为小剂量长程预防、小剂量长程治疗及大剂量短程治疗三种.用肺重/体重、肺虫荷量及肺泡卡氏肺孢子虫(Pc)感染率3项指标考核防治效果.结果抽样检查证实大鼠已成功诱导PCP,均为重度感染.方差分析及卡方检验显示,用双氢青蒿素防治的三组大鼠的三项指标均明显低于两个未防治对照组(P＜0.05或0.01),与甲氧磺胺嘧啶-磺胺甲基异恶唑(TMP-SMZ)标准剂量治疗对照(G)组无显著性差异(P＞0.05).结论双氢青蒿素能有效防治大鼠的PCP,效果与标准剂量TMP-SMZ接近.     

卡氏肺孢子菌肺炎6例的护理

目的探讨卡氏肺孢子菌肺炎(pneumocystis carinii pneumoniapneumocystis,PCP)患者的临床观察和护理,及早发现病情变化,掌握最佳治疗时机。方法选取6例并发卡氏肺孢子菌肺炎的患者根据护理问题采取适当护理措施。结果患者通过护理干预预后改善。结论所涉及的护理措施可应用于PCP患者的临床护理。     

肾移植术后合并卡氏肺孢子菌肺炎患者的护理

目的:探讨肾移植术后合并卡氏肺孢子菌肺炎患者的护理措施。方法:回顾性分析2011年6月~2013年2月我科12例肾移植术后合并肺部卡氏肺孢子菌肺炎的临床护理资料,总结护理方法。结果:本组12例患者均康复出院,救治成功率100%。结论:对肾移植术后并发卡氏肺孢子菌肺炎患者密切病情观察,积极改善缺氧,提供呼吸支持,预防药物不良反应的发生,严格消毒隔离,加强营养支持及心理护理是提高抢救成功率的关键。     

肺孢子菌肺炎2例报告并文献复习

肺孢子菌肺炎(pneumocystis pneumonia,PCP)是免疫功能妥协人群常见的急性、亚急性致命性肺炎,其病原体称为肺孢子菌或卡氏肺囊虫.PCP的临床症状和体征不典型,容易误漏诊.现将2例PCP结合文献报道如下.     

卡泊芬净联合复方磺胺甲噁唑治疗艾滋病合并肺孢子菌肺炎临床观察

目的探讨卡泊芬净联合复方磺胺甲噁唑(TMP-SMZ)治疗艾滋病合并肺孢子菌肺炎(PCP)的临床疗效。方法采集我科收治的102例接受卡泊芬净联合TMP-SMZ治疗的艾滋病合并PCP患者的临床资料,同时选取102例年龄、性别和入院病情相匹配的单独使用TMP-SMZ治疗的患者作为对照,分析两组治疗效果。结果经抗PCP治疗后,联合组动脉氧分压(PaO2)、血浆真菌β-(1,3)-D-葡聚糖和血清乳酸脱氢酶(LDH)的变化分别为(13.4±7.9)mmHg(1mmHg=0.133kPa)、(123.9±84.6)ng/L和(104.5±58.9)U/L,而单药组分别为(10.2±6.7)mmHg、(98.6±83.7)ng/L和(87.3±63.4)U/L,两组比较差异具有统计学意义(P=0.002、0.033、0.046),两组白细胞计数、肝肾功能比较差异无统计学意义(P0.05);联合组治疗有效率高于单药组(93.1%vs 82.4%,P=0.034)。结论卡泊芬净联合TMP-SMZ在艾滋病合并PCP治疗中疗效优于单独使用TMP-SMZ,值得在临床工作中进一步验证和推广。     

血浆1,3-β-D葡聚糖对卡氏肺孢子菌肺炎的诊断价值

目的探讨应用血浆1,3-β-D葡聚糖(BG)用于诊断卡氏肺孢子菌肺炎的临床价值。方法选取确诊卡氏肺孢子菌肺炎(PCP)的患者50例,卡氏肺孢子菌(PC)定植的患者50例及同期非PC定植的患者50例,检测其血浆中的BG浓度。结果 PCP患者血浆BG的中位数是698.5pg/mL[四分位距(IQR):184.4~1 256.0pg/mL],高于PC定植患者和非PC定植患者的血浆BG中位数66.5pg/mL(IQR:50.0~91.0pg/mL)、135.9pg/mL(IQR:54.0~556.3pg/mL)。PCP患者血浆BG的平均水平是(1 022.8±982.6)pg/mL,明显高于PC定植[(74.7±33.6)pg/mL]和非PC定植[(562.7±934.9)pg/mL]患者血浆BG的平均水平,差异有统计学意义(P0.05)。以151.5pg/mL为阳性临界值时,血浆BG诊断PCP的敏感性、特异性、阳性预测值和阴性预测值分别是96.0%、74.0%、64.9%和97.4%。以血浆BG作为PCP的诊断方法时,AUC为0.89。结论血浆BG可以作为PCP的一个早期诊断指标,同时可以根据BG结果鉴别PCP或PC定植。     

Dapsone-induced methemoglobinemia in pediatric oncology patients: Case examples

Over the last 25 years, significant advances have been made in supportive care of the immunocompromised patient. One significant advance is the use of trimethoprim-sulfamethoxazole (TMP-SMZ) in the prevention of Pneumocystic carinii pneumonia (PCP). Although TMP-SMZ remains the drug of choice for PCP prophylaxis, children who develop or have a history of adverse reactions must be prescribed an alternative treatment. In these instances, medications such as dapsone, aerosolized pentamidine, or atovaquone are prescribed. This report discusses four children with sulfa allergy who were prescribed dapsone and later developed methemoglobinemia. Although methemoglobinemia is associated with dapsone, there was no reference found regarding this link in the pediatric oncology literature. The purpose of these clinical examples is to alert the pediatric nurse and advanced practitioner to the association of dapsone and methemoglobinemia.     

Efficacy of diaminodiphenylsulfone and other drugs in murine Pneumocystis carinii pneumonitis.

The purpose of this study was to identify new drugs for the prevention and treatment of Pneumocystis carinii pneumonitis (PCP) induced in rats by continuous daily dosage with dexamethasone. Initially, test drugs were administered prophylactically as a screen for efficacy. Drugs were selected because of their known activity against certain protozoa and their tolerance in human usage. Doses were based on previous studies in rats or estimated from usage in humans and lower animals. Allopurinol (50 mg/kg per day), ketoconazole (25 mg/kg per day), difluoromethylornithine (2.5 g/kg per day), diloxanide (125 mg/kg per day, nifurtimox (100 mg/kg per day), suramin (20 mg/kg per day), melarsoprol (20 mg/kg per day), gentian violet (0.5 mg/kg per week, 5 and 50 mg/kg per day), primaquine (5.6 mg/kg per day) and chloroquine (37.5 mg/kg per day) were ineffective, whereas diaminodiphenylsulfone (daspone) (25 mg/kg per day) was totally effective in preventing the infection. Diaminodiphenylsulfone was then evaluated at dose levels of 5, 25, and 125 mg/kg per day and compared with trimethoprim-sulfamethoxazole (TMP-SMZ), given at 50 per 250 mg/kg per day orally. The two highest dose levels of diaminodiphenylsulfone and TMP-SMZ prevented the infection in all of the animals, and the lowest dose of diaminodiphenylsulfone prevented it in 40% of the rats. All of the untreated controls developed PCP. To determine therapeutic efficacy, animals with extensive PCP were treated for 2.5 weeks with diaminodiphenylsulfone or TMP-SMZ. Based on residual extensive pneumonitis at the completion of treatment, the pneumonitis was reduced to 50% by TMP-SMZ and to 25% by diaminodiphenylsulfone, whereas 100% of untreated controls had extensive PCP. When treatment was begun earlier in the course of the pneumonitis, diaminodiphenylsulfone was totally effective in eradicating the infection. These results suggest that diaminodiphenylsulfone is an effective drug for the treatment and prevention of murine PCP and that it is at least as effective as TMP-SMZ.     

Acute bacterial diarrhoea in the emergency room: therapeutic implications of stool culture results.

Empiric treatment with ciprofloxacin and norfloxacin has been recommended recently for patients with acute diarrhoeal disease. In a retrospective 6-month study period the results of stool cultures from 209 patients with acute diarrhoea admitted to the emergency room were analysed. Seventy-eight cultures (37%) were positive for one or more bacteria. Shigella was the most commonly isolated pathogen (68%). Shigella sonnei comprised 72% and Shigella flexneri 19% of all the bacterial isolates. While no antimicrobial resistance to ciprofloxacin was found for both Shigella species, only 36 and 26% of the Shigella isolates were sensitive to ampicillin and trimethoprim-sulfamethoxazole (TMP-SMZ), respectively. These findings point out to the emergence of drug resistance to commonly used antimicrobial drugs. Shigella's high sensitivity to the newer quinolones should make this the treatment of choice for the very sick patient, although physicians should be cautioned to the fact that indiscriminate use of this drug could result in the emergence of resistance similar to that noted with ampicillin and TMP-SMZ.     

Urinary tract infections and antibiotic resistance

Urinary tract infections (UTI) are diseases which differ considerably regarding pathogenesis, natural history and management. Complicated UTI as well as uncomplicated acute pyelonephritis in women are managed with pretherapy urine and, possibly, blood culture. This is not the case, however, with the most frequent UTI, acute uncomplicated cystitis in women. Empirical management strategies, without pretherapy culture, are well established and widely used. The treatment of choice is trimethoprim-sulfamethoxazole (TMP-SMZ) and fluoroquinolones. E. coli cause the vast majority of these infections, and resistance to TMP-SMZ has been observed to increase considerably during the last decade. Data from Europe and Switzerland regarding resistance of etiologic agents causing acute uncomplicated cystitis are very limited. Indeed, these empirical management strategies have resulted in poor microbiological information, since only selected groups of women with UTI undergo urine culture. Data derived from laboratory isolates usually lack the necessary clinical and epidemiological correlations. Preliminary data allow some estimates of the clinical and microbiological success rates when treating TMP-SMZ resistant uropathogens with TMP-SMZ. TMP-SMZ should probably no longer be used if the prevalence of TMP-SMZ resistance among uropathogens causing acute uncomplicated cystitis is 20% or higher. In these cases, a fluoroquinolone during three days, amoxicillin-clavulanate during three to five days or nitrofurantoin during seven days should be given empirically. Non-antibiotic means of preventing UTI, such as increasing colonization resistance with lactobacilli, or the use of vaccines which provide inhibition of adherence of uropathogens to uroepithelial cells, show very promising experimental results. In order to survey and correct the value of our empirical strategies, more appropriate data on antimicrobial resistance and risk factors in the community are needed. This data can only be produced by a strong collaboration effort with networks of general practitioners.     

Efficacies of atovaquone,pentamidine, and trimethoprim/sulfamethoxazole for the prevention of Pneumocystis jirovecii pneumonia in patients with connective tissue diseases

Background

Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients on steroid therapy for connective tissue diseases. The standard agent for primary PCP prophylaxis is trimethoprim/sulfamethoxazole (TMP-SMX), although this agent can cause common adverse reactions, including myelosuppression and renal toxicity, that result in cessation. Aerosolized pentamidine and oral atovaquone are alternatives for PCP prophylaxis. The efficacies of atovaquone, pentamidine, and TMP-SMX to prevent PCP in patients with connective tissue diseases have never been compared.

非人类免疫缺陷病毒感染的肺孢子菌肺炎患者的临床特征

【目的】探讨非人类免疫缺陷病毒(HIV)感染的肺孢子菌肺炎(PCP)患者的临床特征。【方法】收集2018年10月至2019年9月在本院呼吸与危重症医学科诊治的非HIV感染的PCP患者的临床资料,分析其临床特征。【结果】研究纳入45例患者,19例(42.2%)死亡。基础疾病中最常见的为自身免疫性疾病,其次为恶性肿瘤、实体器官移植术后及肾脏疾病;PCP患者主要表现为非特异性的发热、咳嗽、呼吸困难,典型的胸部CT影像为双肺多发或散在磨玻璃影。和住院期间存活的患者相比,死亡患者入院时白蛋白更低(33.9±5.0vs27.7±4.3),乳酸脱氢酶更高(390.7±189.1vs524.1±246.9),血浆尿素氮水平更高[6.1(5.2~8.0)vs9.4(5.0~15.5)],氧合指数更差[371.4(316.2~423.8)vs300.0(257.1~354.8)],其差异均有统计学意义(均P<0.05)。入院后44例均使用复方磺胺甲噁唑抗PCP治疗,其中31例联合使用卡泊芬净;41例(91.1%)患者在抗感染基础上接受糖皮质激素治疗。【结论】非HIV感染的PCP患者病死率较高,入院时低白蛋白、血浆乳酸脱氢酶和尿素氮升高及氧合指数差的患者预后不良。     

Safety and efficacy of reduced-dose pentamidine as second-line treatment for HIV-related pneumocystis pneumonia

ObjectivesParenteral pentamidine isethionate (PM) 4 mg/kg/day is recommended as an alternative therapeutic regimen after failure of first-line treatment for pneumocystis pneumonia (PCP). However, the dose is often reduced to 3 mg/kg/day in clinical settings because of high rates of adverse events and drug toxicity. Although considered equally efficacious, this lower dose has not been well evaluated.MethodsThis was a single-center, retrospective cohort study that analyzed 75 patients with HIV-PCP who were treated with trimethoprim-sulfamethoxazole, but discontinued treatment because of treatment failure or adverse events; they were then administered 3 mg/kg/day of intravenous PM as a salvage therapy. The primary outcomes were the regimen completion rate with the reduced PM dose.Results and conclusionsIn total, 40 (53.3%) of the eligible patients completed PCP therapy with reduced-dose PM salvage treatment. The overall survival rate of PCP was 73 (97.3%). The median duration of second-line PM treatment was 8.0 days (interquartile range: 6.0–10.0). Although, the adverse events with reduced-dose PM were observed in 41 (54.7%), including 35 treatment-limiting adverse events, grade 3 or 4 adverse events occurred in only three patients (thrombocytopenia, one patient; neutropenia, two patients). Life-threating adverse events, such as hypoglycemia and arrhythmia, were not observed with reduced-dose PM. Salvage therapy with reduced-dose PM for patients with HIV-PCP is relatively safe and effective; moreover, life-threating adverse events did not occur. This therapy could be recommended for patients with HIV-PCP who fail to respond to first-line treatment with trimethoprim-sulfamethoxazole.     

Therapy of Antimicrobial-Resistant Typhoid Fever

Antimicrobial-resistant typhoid fever in Saigon was studied by examining in vitro antimicrobial susceptibilities of Salmonella typhi strains and conducting a randomized clinical trial of ampicillin and trimethoprim-sulfamethoxazole (TMP-SMZ). Isolates of S. typhi were obtained from blood or stool cultures of 90 patients. Of 87 isolates tested for antimicrobial susceptibility, 65 (75%) were resistant (R) to chloramphenicol, streptomycin, sulfonamide, and tetracycline, and 22 (25%) were susceptible (S). The drug resistance was transferable to Escherichia coli and was found in 11 different Vi-phage types. All isolates were susceptible to ampicillin and to TMP-SMZ. Agar dilution studies of TMP and SMZ showed synergistic inhibition of growth in all 18 S isolates and in 12 of 48 R isolates tested. The clinical trial of ampicillin and TMP-SMZ showed that both drugs were equally effective. Treatment failure with both drugs was more frequent in patients with S isolates than in patients with R isolates. Therefore, in an area where antimicrobial-resistant typhoid fever exists, patients with R isolates should receive either ampicillin or TMP-SMZ, but patients with S isolates should be treated with chloramphenicol.     

Efficacy of MK-991 (L-743,872), a Semisynthetic Pneumocandin,in Murine Models of Pneumocystis carinii

In addition to its potent efficacy in animal models against Candida sp., Aspergillus fumigatus, and Histoplasma capsulatum, the clinical candidate pneumocandin MK-991 (formerly L-743,872) was also extremely potent against Pneumocystis carinii in models of immune-compromised animals. MK-991 was approximately 14 times more potent than the original natural product lead, pneumocandin B₀. The 90% effective dose (ED₉₀) of MK-991 for cyst clearance in the rat model for pneumocystis was 0.011 mg/kg of body weight when delivered parenterally for 4 days twice a day (b.i.d.). In a mouse model, under the same experimental parameters, the ED₉₀ was 0.02 mg/kg. MK-991 was also effective orally, with an ED₉₀ for cyst clearance of 2.2 mg/kg against acute infection in rats (b.i.d. for 4 days). Complete prevention of P. carinii development was achieved in immunocompromised mice at a daily oral dose of 2.25 mg/kg. As reported previously for other pneumocandins and echinocandins, MK-991 selectively prevented the development of P. carinii cysts. When used as a prophylactic agent, neither stage of the organism appeared in the lungs of animals. In response to an acute infection, cysts were eliminated rapidly, while trophozoite forms persisted. Despite good efficacy as an oral agent in murine models, the low oral absorption of this class may limit the use of MK-991 to parenteral therapy.Pneumocystis carinii is one of the most common and serious opportunistic infections in patients with AIDS, as well as in those receiving immunosuppressive therapy as a result of organ transplantation or cancer chemotherapy. The most widely used agent for the treatment and prevention of P. carinii pneumonia (PCP), trimethoprim-sulfamethoxazole (TMP-SMZ), has a high incidence of adverse reactions in AIDS patients (2). Rapid oral desensitization to TMP-SMZ has been attempted (5, 8, 10), and while initial results are positive, studies have been limited to small numbers of patients, and there is clearly a need for a new class of compounds to treat PCP.A novel natural product, pneumocandin B₀, originally isolated from a fermentation of Glarea lozoyensis, was found to have activity in an experimental rat model for PCP (13). Synthetic chemical modifications of the parent structure have resulted in more potent and soluble compounds (12). The pneumocandins act by inhibiting the synthesis of β- 1,3-glucan, a major component of the cyst wall of P. carinii (7). The lack of a mammalian β-1,3-glucan synthase counterpart should provide a superior therapeutic window over standard PCP treatments, such as TMP-SMZ and pentamidine.While β-1,3-glucan represents a major portion of the wall of the cyst, it is not found in great abundance in the trophozoite form of the organism. From previous studies (13), we know that short-term treatment (4 days) with pneumocandin analogs does not have a significant effect on trophozoites. Treatment over a period of 2 weeks (the standard length of treatment for known PCP agents) results in no significant increase or decrease in the level of trophozoites. This result suggests that inhibition of cyst proliferation has an effect on the ability of the trophozoites to multiply. Finally, when prophylactic effects of the pneumocandins were evaluated, inhibition of the cyst form of the organism was found to result in inhibition of the trophozoite form as well, implying that the cyst stage is required for trophozoite proliferation (11).The efficacy of one of the most potent semisynthetic pneumocandins, MK-991, against PCP is evaluated here. This compound was evaluated orally (p.o.) and parenterally in murine models for PCP. Short-term (4 day) and long-term (as much as 21 days) uses, as well as prophylactic use, were evaluated. In addition, the effects of the drug on the organization of the cyst and localization of the drug in the cyst wall after 2 days of drug treatment were evaluated.