肺结核患者合并肺部感染的病原菌分布及耐药性分析

目的探讨肺结核患者合并肺部感染的病原菌分布特点及耐药性,为临床合理用药和控制医院内感染提供依据。方法对2009年1月至2011年12月该院肺结核患者合并肺部感染时下呼吸道标本中分离出的阳性标本进行病原菌及耐药性分析。结果分离病原菌510株,其中革兰阴性杆菌占65.88%,真菌占19.02%,革兰阳性球菌占15.10%。感染前5位病原菌为铜绿假单胞菌(18.04%)、肺炎克雷伯菌(11.96%)、鲍曼不动杆菌(11.18%)、金黄色葡萄球菌(10.39%)和白假丝酵母菌(10.00%)。革兰阴性杆菌对氨苄西林、头孢唑啉耐药率大于97.00%。铜绿假单胞菌对亚胺培南耐药率(15.22%)最低,鲍曼不动杆菌对头孢哌酮/舒巴坦耐药率(21.05%)最低,肺炎克雷伯菌、阴沟肠杆菌、大肠埃希菌对亚胺培南全部敏感(100.00%),革兰阳性球菌对万古霉素敏感率为100.00%。结论革兰阴性杆菌、真菌是该院肺结核患者合并肺部感染的常见病原菌,多药耐药性较高,临床医生应根据药敏试验结果选择合理的抗菌药物。     

Treatment of vancomycin-resistant enterococcal infections in the immunocompromised host: quinupristin-dalfopristin in combination with minocycline

Between February 1994 and November 1998, 56 oncology patients infected with vancomycin-resistant enterococci (VRE) were treated with quinopristin-dalfopristin (Q-D) plus minocycline (MIN). Infections included bacteremia, urinary tract infection, pneumonia, and wound infection. The response rate was 68%, and the most frequent adverse event was arthralgia or myalgia (36%). Q-D-MIN is effective for VRE infection in cancer patients but is associated with a substantial frequency of arthralgia or myalgia.     

Two decades of imipenem therapy

Imipenem, the first carbapenem discovered, was developed more than two decades ago in response to an unmet need for a highly potent, broad-spectrum antimicrobial agent with a strong safety profile. It has since been used to treat more than 26 million patients. In an era where antibiotic use has driven antibiotic resistance, choosing appropriate initial therapy for serious infection is critical. Appropriate antibiotic regimens must cover all likely pathogens, be administered promptly at the correct dosage and dosing interval, be well tolerated and prevent the emergence of resistance. While imipenem was initially reserved for use in intractable, serious infections, the benefits of early aggressive therapy are now known, making imipenem a core agent in de-escalation therapy due to proven efficacy and safety for indications such as nosocomial pneumonia, intra-abdominal infection, sepsis and febrile neutropenia. De-escalation therapy with an agent such as imipenem minimizes resistance development by initiating aggressive initial treatment and then tailoring therapy based on patient response and culture results, switching to a less expensive, narrower spectrum antibiotic regimen or shortening the duration of therapy. Imipenem has maintained sustained clinical efficacy, tolerability and in vitro activity against important bacterial pathogens for two decades. We review the factors that continue to make imipenem as appropriate an agent for de-escalation therapy now as it was 20 years ago.     

老年重症肺炎患者的抗菌药物降阶梯治疗策略与利奈唑胺的临床应用

目的使用降阶梯方案治疗呼吸科重症监护病房（RICU）老年重症肺炎患者并评价其疗效。方法回顾性分析我院2009年11月至2010年11月RICU老年重症肺炎患者40例,分成传统治疗组和降阶梯治疗组,比较两组患者的初始治疗恰当率、感染控制率和感染控制所需时间等指标。结果降阶梯治疗组与传统治疗组的初始治疗恰当率分别为82.5%与50.5%,差异有统计学意义（P〈0.05）;治疗有效率分别为85.5%、50.0%,差异有统计学意义（P〈0.05）;感染控制所需天数分别为71、2 d,差异有统计学意义（P〈0.05）。结论对于RICU老年重症肺炎患者,使用降阶梯治疗可获得良好疗效。     

196株阴沟肠杆菌对抗菌药物的敏感性分析

目的了解全身感染和尿液感染的阴沟肠杆菌对抗菌药物的敏感性,为临床提供治疗依据。方法采用微量稀释法对196株临床送检的血液、尿液及其他标本分离的阴沟肠杆菌进行药敏试验,测定其最低抑菌浓度值。结果阴沟肠杆菌对亚胺培南的敏感率为96.9%,对哌拉西林/他唑巴坦、左氧氟沙星、环丙沙星、庆大霉素、妥布霉素的敏感率为60%～80%,对头孢他啶、氨曲南、头孢曲松、哌拉西林的敏感率为40%～60%,对氨苄西林/舒巴坦的敏感率为14.3%,对氨苄西林和头孢唑啉的敏感率仅为3.6%和1.5%;分离自尿液的阴沟肠杆菌对氨苄西林/舒巴坦、头孢唑啉的敏感性高于血液分离菌,分离自尿液的阴沟肠杆菌对氨苄西林、头孢他啶、头孢曲松、环丙沙星、庆大霉素、亚胺培南、左氧氟沙星、氨曲南、哌拉西林、哌拉西林/他唑巴坦、妥布霉素的敏感性低于血液分离菌。结论阴沟肠杆菌对不同的抗菌药物的敏感性差异较大,治疗时应根据耐药特点及菌种间的耐药性差异选择相应的药物和方案,目前亚胺培南仍然是治疗阴沟肠杆菌感染的有效药物。     

Ofloxacin versus standard therapy in treatment of community-acquired pneumonia requiring hospitalization. Pneumonia Study Group.

Community-acquired pneumonia occurs 3 to 4 million times per year in the United States, accounting for about 500,000 hospitalizations annually. Empiric treatment is usually instituted because of a lack of early organism-specific diagnostic tests. This study compared empiric therapy with ofloxacin to standard antibiotic regimens (usually a beta-lactam with or without a macrolide) for patients hospitalized for community-acquired pneumonia. Therapy was administered to 298 patients (146 receiving ofloxacin and 152 receiving standard therapy); 227 patients (ofloxacin, 109; standard treatment, 118) were evaluable for treatment efficacy. The most common pyogenic respiratory pathogens were Haemophilus influenzae (30 isolates) and Streptococcus pneumoniae (24 isolates). There was evidence of infection with either Mycoplasma pneumoniae (38 patients), Chlamydia pneumoniae (40 patients), or a Legionella sp. (8 patients) in a total of 79 patients (35%). The clinical success rates were similar in both groups among evaluable patients (92%, ofloxacin; 87%, standard therapy) and among patients with atypical respiratory pathogens (88%, ofloxacin; 81%, standard therapy). The mean numbers (+/- the standard deviations) of intravenous doses of antibiotics were 7.5 +/- 8.0 in the ofloxacin group and 18.4 +/- 18.5 in the standard therapy group (P < 0.001); the mean number of oral doses of ofloxacin per patient was 19.7 +/- 11.2, compared with 30.2 +/- 16.0 oral antibiotic doses in the standard therapy group (P < 0.001). All treatments were well tolerated and associated with no significant clinical or laboratory abnormalities. The findings of this study indicate that ofloxacin is active against traditional bacterial pathogens as well as the major atypical respiratory pathogens. When given as monotherapy for the empiric treatment of community-acquired pneumonia, ofloxacin is as effective as standard antimicrobial therapy.     

Risk factors of mortality for nosocomial pneumonia: importance of initial anti-microbial therapy

Nosocomial pneumonia is a common nosocomial infection and has high mortality rate. Risk factors of mortality of nosocomial pneumonia were studied in 132 hospitalised patients who developed nosocomial pneumonia. The overall mortality rate was 64/132, 48.5%. Of the 11 risk factors univariately associated with mortality due to nosocomial pneumonia, only the inappropriate initial anti-microbial therapy, high simplified acute physiology score and multiple organ failures remained significant after stepwise logistic regression. Gram-negative bacilli were still the most pre-dominant causative microbiologic agents of nosocomial pneumonia with Pseudomonas aeruginosa (20.3%), Acinetobacter baumannii (18.6%) and Escherichia coli (5.9%) being the three most predominant pathogens. A. baumannii were significantly more predominant among non-survivors than survivors (13.56 vs. 5.08%, p=0.0418). The incidence rate of methicillin-resistant Staphylococcus aureus was 19.5% higher than previous reports. We conclude that inappropriate initial anti-microbial therapy for nosocomial pneumonia is associated with the mortality rate of nosocomial pneumonia, and appropriate anti-microbial therapy improves outcome of nosocomial pneumonia.     

绿脓杆菌制剂辅助治疗肺癌临床研究

目的:评价Ⅱ类新生物制品绿脓杆菌制剂(PA-MSHA)作为免疫调节剂的有效性和安全性。方法:采用非盲法随机对照试验。试验组肺癌患者20例,对照组20例。两组采用同样的化疗方案,试验组加用绿脓杆菌制剂。治疗结束后评价疗效和感染率,并在治疗前后分别检测患者免疫功能。结果:试验组有效率(CR PR)为65%,对照组45%(P<0.01);试验组感染率为15%,对照组为40%(P<0.05);试验组治疗后C3、C4、CD4/CD8比值、NK细胞活性和IL-2水平均高于对照组(P<0.05)。试验组中3例患者出现不良反应,均自行缓解。结论:绿脓杆菌制剂能明显提高肺癌患者的免疫功能,与化疗药物合用可提高疗效,并有预防感染作用。     

Treatment of scedosporiosis with voriconazole: clinical experience with 107 patients

The efficacy of voriconazole in 107 patients with scedosporiosis was analyzed. Principal infection sites were the lungs/sinuses (24%), central nervous system (CNS) (20%), and bone (18%), while 21% of patients had disseminated infection. Solid organ transplantation (22%), hematological malignancy (21%), and surgery/trauma (15%) were the predominant underlying conditions. A successful therapeutic response was achieved in 57% of patients (median, 103 therapy days), with > 98% of those responding receiving > or = 28 days of therapy. Patients receiving primary therapy showed a 61% response versus 56% for the others. The best therapeutic responses were seen for skin/subcutaneous (91%) or bone (79%) infections, and the lowest for CNS infections (43%). Patients without major immune suppression (72%) or those with solid organ transplantation (63%) or various hematological conditions (60%) showed the best responses by underlying condition. Median known survival time was 133 days (therapy successes, 252 days; failures, 21 days). In all, 43 (40%) patients died, 73% due to scedosporiosis. Patients with Scedosporium prolificans infection had significantly reduced survival times (P = 0.0259) and were more likely to die from fungal infection (P = 0.002) than were Scedosporium apiospermum-infected patients. In a subset of 43 patients where voriconazole baseline MICs were available, response to voriconazole was higher for S. apiospermum-infected patients (54% response; MIC(50), 0.25 microg/ml) than for S. prolificans-infected patients (40% response; MIC(50), 4.0 microg/ml). Voriconazole demonstrated clinically useful activity in the treatment of both S. apiospermum and S. prolificans infections and was well tolerated.     

Clinical and microbiological efficacy of tigecycline for complicated skin‐soft‐tissue and intra‐abdominal infections in a Turkish university hospital

Objective:  Tigecycline, a new glycylcycline antimicrobial agent, is indicated for the treatment of complicated skin structure infection (cSSTI), intra‐abdominal infection (cIAI) and community acquired pneumonia. We aimed to evaluate the clinical and microbiological data together about tigecycline therapy. Methods:  Patients with cIAIs and cSSTIs were included in a prospective, observational follow‐up. Patient follow‐up forms were developed and clinical and microbiological data were recorded. Results:  Of the 107 patients, 67 had cSSTIs, 40 had cIAIs. Tigecycline was used empirically in 37.5% of cIAIs and in 50.7% of cSSTIs. In 85.0% of the patients with cIAI and in 73.1% of the patients with cSSTI, clinical and/or microbiological response could be achieved. A drug change was made in 26.9% and 7.5% of the patients with cSSTI and cIAI respectively. Superinfection was detected in 14.9% of the cSSTI and 7.5% of the cIAI patients. Conclusion:  As a result, tigecycline can be safely used in the treatment of different infections. Compared with cSSTIs, the treatment response is better and the duration of treatment is shorter in cIAIs. However, MIC value must be determined at any rate if tigecycline is to be used in the treatment of Acinetobacter (MDR Acinetobacter, in particular) infections. Clinical cure and microbiological eradication rate of tigecycline therapy changes according to different clinical diagnosis and microorganism.     

Observational study in a single institute in Japan: How many community-onset pneumonia patients would have Clostridioides difficile infections after treatment?

While community-onset pneumonia patients such as community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) have several risk factors of Clostridium difficile infection (CDI), prognostic guidelines for pneumonia never mention the occurrence of CDI following treatment for pneumonia. For the purpose of examining the occurrence and prevalence of CDI, we reviewed all community-onset pneumonia patients who were admitted to our institute during the study period.A total of 406 patients were enrolled in this study. Among them, 257 patients (63%) were male, and the median age was 79 years (range 19–103 years). Surprisingly, 155 CAP (88%) and all HCAP (100%) patients had one or more risk factors for CDI. Furthermore, 70 CAP (40%) and 157 HCAP (69%) patients had more than 3 risk factors for CDI. Despite these facts, probiotic medication for prevention of CDI were prescribed for 12 (7%) CAP and 15 (7%) HCAP patients as the initial treatment. Finally, 3% and 9% of CAP and HCAP patients had CDI after completing the treatment for pneumonia. Regarding the duration of antibiotic therapy, 146 CAP (82%) and 176 HCAP (77%) patients received it for longer than 8 days, even though bacteremia was not confirmed in those patients. In addition, 27 CAP (15%) and 26 HCAP (11%) patients received a combination antibiotic therapy as an initial treatment. They seemed to be unnecessary. Physicians should acknowledge community-onset pneumonia has several risk factors for CDI, and should avoid a longer than necessary antibiotic therapy and unnecessary combination antibiotic therapy for pneumonia patients with risk factors for CDI.     

Type III protein secretion is associated with poor clinical outcomes in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa

OBJECTIVE: Pseudomonas aeruginosa is a frequent cause of ventilator-associated pneumonia. Recent evidence suggests that production of type III secretion proteins is correlated with increased pathogenicity in both cellular and animal models of infection. The objective of this study was to determine whether this system contributes to disease severity in humans with ventilator-associated pneumonia. DESIGN: Retrospective pilot cohort study. SETTING: University hospital. PATIENTS: Thirty-five mechanically ventilated patients with bronchoscopically confirmed ventilator-associated pneumonia caused by P. aeruginosa. MEASUREMENTS AND MAIN RESULTS: Ventilator-associated pneumonia was categorized as severe (patients died or had a recurrence of their pneumonia despite appropriate antibiotic therapy) or mild (patients uneventfully recovered from their pneumonia). The type III secretion genotypes and phenotypes of isolates cultured from the patients with ventilator-associated pneumonia were determined. Whereas every examined isolate harbored type III secretion genes, only 27 (77%) were capable of secreting detectable amounts of type III proteins in vitro. Twenty-two (81%) of the patients infected with these 27 isolates had severe disease. Of the eight isolates that did not secrete type III proteins, only three (38%) were cultured from patients with severe disease. Thus, infection with a type-III-secreting isolate correlated with severe disease (p < .05). In vitro assays indicated that ExoU, the type III effector protein most closely linked to mortality in animal models, was secreted in detectable amounts in vitro by 10 (29%) of the 35 examined isolates. Nine (90%) of these 10 isolates were cultured from patients with severe disease (p < .05 when compared with the nonsecreting isolates). In contrast, ExoS was secreted by 16 (46%) of the 35 examined isolates. Twelve (75%) of these 16 isolates were cultured from patients with severe disease (p = .14 when compared with the nonsecreting isolates). CONCLUSIONS: In patients with ventilator-associated pneumonia, type-III-secreting isolates were associated with worse clinical outcomes, suggesting that this secretion system plays an important role in human disease. Our findings support the hypothesis that antibodies targeted against these proteins may be useful as adjunctive therapy in intubated patients with P. aeruginosa colonization or infection.     

Impact of imipenem resistance on mortality in patients with Acinetobacter bacteraemia

OBJECTIVES: To investigate the impact of imipenem resistance on the mortality rate among patients with Acinetobacter bacteraemia. METHODS: A retrospective, pairwise-matched (1:1), risk-adjusted (age, Pitt bacteraemia score) cohort study was performed at three tertiary care hospitals in Korea from January 2000 to June 2005. RESULTS: Forty patients with imipenem non-susceptible Acinetobacter bacteraemia (INAB group) and 40 matched subjects (1:1 ratio) with imipenem-susceptible Acinetobacter bacteraemia (ISAB group) were included. Both groups had similar clinical features related to the severity of illness. The 30 day mortality rate was higher in the INAB group (57.5%) than the ISAB group (27.5%) (P = 0.007). The rate of discordant antimicrobial therapy was higher in the INAB group (65.0%) than the ISAB group (20.0%) (P < 0.001). The 30 day mortality rate was higher in the patients with discordant antimicrobial therapy (67.6%) than concordant antimicrobial therapy (23.9%) (P < 0.001). Multivariate analysis showed that age, the Pitt bacteraemia score, immunosuppressive status, and discordant antimicrobial therapy were independent risk factors for 30 day mortality among patients with Acinetobacter bacteraemia (P < 0.05). When discordant antimicrobial therapy was excluded in the multivariate analysis, the imipenem resistance was associated with 30 day mortality (P = 0.005). CONCLUSIONS: Imipenem resistance has a significant impact on the mortality rate among patients with Acinetobacter bacteraemia, and this is mainly attributable to the higher rate of discordant antimicrobial therapy.     

Ventilator-associated pneumonia: breaking the vicious circle of antibiotic overuse

OBJECTIVE: To assess the rate of appropriateness of empirical antimicrobial therapy for ventilator-associated pneumonia, to evaluate de-escalation in patients with ventilator-associated pneumonia treated according to local pathway, and to identify the bacteria responsible for recurrence of ventilator-associated pneumonia. DESIGN: Prospective observational study during a 36-month period. SETTING: Medical-surgical intensive care unit of a university hospital. PATIENTS: One hundred and fifteen patients hospitalized in an intensive care unit developing ventilator-associated pneumonia with positive cultures. The patients with ventilator-associated pneumonia were treated with limited-spectrum antibiotics (i.e., without activity against Pseudomonas aeruginosa) if they had no prior hospitalization (within 21 days) or prior administration of antibiotics (within 10 days). Quantitative cultures obtained by bronchoscopy or tracheal aspiration were used to reassess empirical therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A limited-spectrum therapy was used in 79 patients (69%). Empirical antimicrobial therapy was appropriate in 100 patients (85%). The mortality rate was significantly higher in the patients in whom empirical therapy was inappropriate than in those in whom treatment was appropriate (47 vs. 20%, p=.04). De-escalation was done in respectively 26% and 72% of patients with early- and late-onset ventilator-associated pneumonia, whereas treatment was escalated in 27 patients (23%). Ventilator-associated pneumonia episodes were recurrent in 22 cases, including eight episodes due to high-risk bacteria. CONCLUSIONS: A rational empirical antimicrobial therapy for ventilator-associated pneumonia using limited-spectrum antibiotics is possible if local ecology and patient medical history and clinical status are considered. In addition, de-escalation is feasible in 42% of patients. This integrative approach may reduce the emergence of resistant bacteria, which in turns reduces the need for broad-spectrum antibiotics, breaking the vicious circle of antibiotic overuse.     

Ampicillin versus cefamandole as initial therapy for community-acquired pneumonia.

One hundred seven patients with community-acquired pneumonia thought to be of bacterial etiology by the admitting physician but whose initial sputum Gram stain was inadequate to direct specific therapy were randomized to receive either intravenous ampicillin or cefamandole as empiric therapy. Patients were excluded if the initial sputum Gram stain was highly suggestive of infection with Streptococcus pneumoniae, Staphylococcus aureus, or an enteric gram-negative bacillus. The two study groups had comparable demographic and presenting clinical features. The mean age of the patients evaluable for determination of clinical efficacy was 69 years, and greater than 75% had at least one serious underlying medical disorder. In the 90 evaluable patients, there were 11 therapeutic failures (12%), including 5 deaths (5%). Cefamandole, a broad-spectrum antibiotic, was not more efficacious than ampicillin in producing a satisfactory clinical response or in shortening the duration of parenteral therapy. Patients received an average of only 4 days of intravenous antibiotics before changeover to oral therapy and were hospitalized for a mean of 7 days. No patient experienced a relapse of pneumonia following successful completion of parenteral drug therapy. We conclude that cefamandole is not a more effective agent than ampicillin for empiric therapy of community-acquired bacterial pneumonia of uncertain etiology.     

Evaluation of aztreonam in the treatment of severe bacterial infections.

We investigated the clinical efficacy and safety of aztreonam in the treatment of 50 episodes of infection in 46 adult patients. The clinical condition of patients at the beginning of treatment was critical or poor in 28 of the episodes of infection. Episodes treated were 39 urinary tract infections (12 of them with concomitant bacteremia), 2 soft tissue infections, 8 patients with osteomyelitis (1 with concomitant bacteremia), and one episode of pneumonia. Significant isolated microorganisms were aerobic or facultative gram-negative rods and were responsible for the following episodes of infection (number of episodes): members of the family Enterobacteriaceae (49), Pseudomonas aeruginosa (5), and Haemophilus influenzae (1). The overall rate of clinical response to aztreonam was 94% of the treated episodes. Colonization or superinfection or both occurred in 29 episodes, but only 8 episodes required antimicrobial therapy. Aztreonam seems to be an effective single agent therapy for many bacterial infections. Colonization and superinfection by Candida sp., Streptococcus faecalis or Staphylococcus aureus must be monitored.     

Modeling the response of pneumonia to antimicrobial therapy.

The response to antimicrobial therapy in patients with pneumonia was assessed by using a previously developed pneumonia scoring system. Patients from two different clinical trials were evaluated. The first group (n = 22) was treated with cefmenoxime. For these patients, doses were adjusted to achieve an area under the plasma concentration-versus-time curve (AUC) above the MIC of 140 microg x h/ml and pneumonia response scores were evaluated retrospectively. The second group (n = 21) were treated with either ciprofloxacin (CIP) or ceftazidime (TAZ) in a randomized clinical trial. Here, doses were adjusted to achieve AUC from 0 to 24 h/MIC values that were > 250 SIT(-1) x h (estimate of the area under the curve of inverse serum inhibitory titer versus time) and pneumonia response scoring was concurrent. In both studies eradication of the pathogen was determined by serial endotracheal cultures and clinical parameters were scored daily. A decrease in total score was indicative of an improving clinical condition. The percent change in clinical daily score was determined for each day of treatment. The rate of clinical response was determined by linear regression of the percent change in daily clinical score versus time during the course of antimicrobial therapy. Factors predictive of time to eradication were explored by interval analysis. Logistic regression was used to determine the earliest time point in therapy at which treatment scores predicted outcome. Kruskal-Wallis analysis of variance was used for statistical analysis, and significance was accepted at P < 0.05. There were no differences in baseline scores at day one for the patients treated with different antibiotics (P = 0.58). For patients with pathogen eradication, a significant difference between the two studies in time to eradication was found: 4.8 days for cefmenoxime-treated patients and 1.4 days for CIP- or TAZ-treated patients (P < 0.001). For patients experiencing bacterial eradication, the rates of clinical change for cefmenoxime and CIP or TAZ treatment were similar (P = 0.77). For patients with organisms that were not eradicated, the rates of change were similar (P = 0.14). There was a significant difference in the rate of change for patients experiencing eradication compared with that for patients in which the organism persisted (P << 0.01). Both treatment group and rate were found to be predictive of days to eradication. There was a significant difference in the percent change in clinical score on day 3 of therapy for patients with bacteria that were eradicated versus those with persistent organisms (P < 0.01). The percent change was more predictive of outcome with each subsequent day. Patients who demonstrated a > or = 10% reduction in clinical score after 72 h of treatment had an 88% probability of bacterial eradication. The clinical scoring system is a useful tool for modeling the response of pneumonia to antimicrobial therapy. The ability to predict outcome relatively early in therapy, by using a scoring system of clinical parameters which can be routinely monitored, will aid in assessing the response to antimicrobial therapy in clinical as well as in research settings.     

亚胺培南／西司他丁钠治疗重症肺炎的疗效观察

目的：观察亚胺培南／西司他丁钠治疗重症肺炎的临床疗效及安全评价。方法：将2008年6月-2012年12月收治90例重症肺炎患者随机分为A、B、C三组各30例,分别使用亚胺培南／西司他丁钠1000mg静脉滴注,每8小时一次;500mg静脉滴注,每6小时一次;500mg静脉滴注,每8小时一次治疗,比较其临床疗效、细菌清除率和安全性。结果：A组、B组的临床疗效、细菌清除率和安全性均明显优于c组,P均〈0．05;但A组、B组间无显著性差异。结论：亚胺培南／西司他丁钠对重症肺炎有良好疗效,使用方法以500mg,静脉滴注,每6小时一次为最适宜。     

Imipenem therapy of Pseudomonas aeruginosa and other serious bacterial infections

Imipenem is the first of a new class of beta-lactam antimicrobial agents with remarkable and extremely potent in vitro activity against most commonly isolated bacterial pathogens, including Staphylococcus aureus, enterococcus, members of the family Enterobacteriaceae, Pseudomonas aeruginosa, Bacteroides fragilis, and Hemophilus influenzae. The clinical efficacy and toxicity of imipenem were evaluated in 35 patients with 38 different infections. The overall clinical response was favorable (infections cured or improved) in 89% of the infections (34 of 38). Of the 17 infections with P. aeruginosa, 15 were cured or improved. However, P. aeruginosa isolates resistant to imipenem emerged during the therapy of six infections, and two cases of P. aeruginosa septicemia later relapsed after imipenem therapy. Gastrointestinal toxicity (nausea with or without emesis) occurred in 17% of the patients (6 of 35) but was ameliorated by slowing the rate of intravenous infusion or lowering the dose of imipenem. Except for certain severe P. aeruginosa infections, imipenem is effective and relatively safe therapy for infections caused by susceptible organisms.     

De-escalation therapy in ventilator-associated pneumonia

OBJECTIVE: To evaluate de-escalation of antibiotic therapy in patients with ventilator-associated pneumonia. DESIGN: Prospective observational study during a 43-month period. SETTING: Medical-surgical intensive care unit. PATIENTS: One hundred and fifteen patients admitted to the intensive care unit with clinical diagnosis of ventilator-associated pneumonia. All the episodes of ventilator-associated pneumonia received initial broad-spectrum coverage followed by reevaluation according to clinical response and microbiology. Quantitative cultures obtained by bronchoscopic examination or tracheal aspirates were used to modify therapy. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS: One hundred and twenty-one episodes of ventilator-associated pneumonia were diagnosed. Change of therapy was documented in 56.2%, including de-escalation (the most frequent cause) in 31.4% (increasing to 38% if isolates were sensitive). Overall intensive care unit mortality rate was 32.2%. Inappropriate antibiotic therapy was identified in 9% of cases and was associated with 14.4% excess intensive care unit mortality. Quantitative tracheal aspirates and bronchoscopic samples (58 protected specimen brush and three bronchoalveolar lavage) were associated with 32.7% and 29.5% intensive care unit mortality and 29.3% and 34.4% de-escalation rate. De-escalation was lower (p < .05) in the presence of nonfermenting Gram-negative bacillus (2.7% vs. 49.3%) and in the presence of late-onset pneumonia (12.5% vs. 40.7%). When the pathogen remained unknown, half of the patients died and de-escalation was not performed. CONCLUSION: De-escalation was the most important cause of antibiotic modification, being more feasible in early-onset pneumonia and less frequent in the presence of nonfermenting Gram-negative bacillus. The impact of quantitative tracheal aspirates or bronchoscopic techniques was comparable in terms of mortality.