Measuring the impact of multidrug resistance in nosocomial infection

PURPOSE OF REVIEW: The review examines potential confounders hampering measurement of the impact of multidrug resistance in nosocomial infections. Methodological techniques dealing with the problem of confounding are discussed and current findings in how multidrug resistance affects outcome in patients with nosocomial infection are highlighted. RECENT FINDINGS: Outcome comparisons between patients infected with multidrug-resistant pathogens and patients infected with susceptible microorganisms are hampered by confounders such as differences in disease severity, prolonged hospitalization prior to onset of infection (exposure time), the causative pathogen, the type of infection, and the rate of appropriate empirical antimicrobial therapy. The confounding effect can be countered by means of either multivariable regression techniques or matched cohort studies, or a combination of both. Recent literature on the impact of multidrug resistance (methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase producing Enterobacteriaceae, etc) is conflicting and highly dependable on the way disturbing variables are accounted for. SUMMARY: Recent data underscore that the impact of multidrug resistance on the outcome of nosocomial infection might differ depending on the study population, type of infection, type of pathogen and appropriateness of therapy, and hence, that any conclusion drawn prior to accurate accounting for imbalanced confounders is premature and potentially false.     

急性白血病化疗后医院感染及抗感染治疗分析

目的:探讨急性白血病(AL)化疗后医院感染(HAI)的易感因素、防治方法及预防措施。方法:对93例初治AL患者住院化疗后的医院感染发生及治疗情况进行回顾性分析。结果:中性粒细胞计数(ANC)降低、年龄>60岁、未能完全缓解(CR)患者医院感染率增高,抗生素联合粒细胞集落刺激因子(G-CSF)治疗使化疗后AL患者发热及ANC恢复天数分别缩短为(7.0±1.89)d和(6.0±1.3)d。结论:AL患者化疗后ANC降低、患者年龄>60岁及未获得CR是医院感染主要易感因素,抗生素加用G-CSF合理应用,能减少医院感染发生率及严重程度。     

The role of the microbiologist in the control of nosocomial infection and antibiotic therapy

The microbiologist is a key figure in the control of hospital infection and in antimicrobial policy. Some of the contributions to the area of documentation and information can be summarized as follows: information on the development of isolation of sentinel microorganisms and their distribution in services and areas, the development of resistance of the various microorganisms to the most commonly used antimicrobial agents, molecular characterization of the isolated microorganisms causing epidemic outbreaks and the control of environmental microorganisms posing a threat to hospitals.Concerning interventions, microbiologists make a substantial contribution to teaching activity and to the continuing education required to maintain optimal knowledge on infections and microbiology in hospitals. They also recommend therapeutic approaches to the presence of isolated microorganisms and specific situations, collaborate in the design of antimicrobial prophylaxis and illustrate the policy of patient isolation. Microbiologists play a key role in decisions to introduce new drugs in hospitals and in programs to limit their inappropriate use.Finally, microbiologists and microbiology services constitute a central element where all the activities required for the diagnosis, treatment and control of infection performed by the various hospital services converge.     

Treatment failure in pneumonia: impact of antibiotic treatment and cost analysis

The aim of this study was to investigate treatment failure (TF) in hospitalised community-acquired pneumonia (CAP) patients with regard to initial antibiotic treatment and economic impact. CAP patients were included in two open, prospective multicentre studies assessing the direct costs for in-patient treatment. Patients received treatment either with moxifloxacin (MFX) or a nonstandardised antibiotic therapy. Any change in antibiotic therapy after >72 h of treatment to a broadened antibiotic spectrum was considered as TF. Overall, 1,236 patients (mean ± SD age 69.6 ± 16.8 yrs, 691 (55.9%) male) were included. TF occurred in 197 (15.9%) subjects and led to longer hospital stay (15.4 ± 7.3 days versus 9.8 ± 4.2 days; p < 0.001) and increased median treatment costs (€2,206 versus €1,284; p<0.001). 596 (48.2%) patients received MFX and witnessed less TF (10.9% versus 20.6%; p < 0.001). After controlling for confounders in multivariate analysis, adjusted risk of TF was clearly reduced in MFX as compared with β-lactam monotherapy (adjusted OR for MFX 0.43, 95% CI 0.27-0.68) and was more comparable with a β-lactam plus macrolide combination (BLM) (OR 0.68, 95% CI 0.38-1.21). In hospitalised CAP, TF is frequent and leads to prolonged hospital stay and increased treatment costs. Initial treatment with MFX or BLM is a possible strategy to prevent TF, and may thus reduce treatment costs.     

Sputum antibiotic concentrations: implications for treatment of cystic fibrosis lung infection

BACKGROUND: The success of antibiotic therapy may be predicted based on the achievement of pharmacodynamic indices (PDIs), which are determined by the susceptibility of the infecting bacteria and the concentrations of antibiotics achieved at the site of infection. The aim of this study was to determine whether PDIs associated with clinical effectiveness for ceftazidime and tobramycin were achieved at the site of infection in the lungs of cystic fibrosis (CF) patients following intravenous administration during treatment of an acute exacerbation. METHODS: Serum and sputum samples were collected from 14 CF patients and the concentration of both antibiotics in the samples determined. The susceptibility of bacteria cultured from sputum samples to both antibiotics alone and in combination was also determined. RESULTS: A total of 22 Pseudomonas aeruginosa isolates and 4 Burkholderia cepacia complex isolates were cultured from sputum samples with 55% and 4% of isolates susceptible to ceftazidime and tobramycin, respectively. Target PDIs for ceftazidime and tobramycin, an AUC/MIC ratio of 100 and a C(max)/MIC ratio of 10, respectively, were not achieved in serum or sputum simultaneously or even individually for any patient. Although the combination of ceftazidime and tobramycin was synergistic against 20 of the 26 isolates cultured, the concentrations of both antibiotics required for synergy were achieved simultaneously in only 38% of serum and 14% of sputum samples. CONCLUSION: Key PDIs associated with clinical effectiveness for ceftazidime and tobramycin were not achieved at the site of infection in the lungs of CF patients.     

流感样疾病的病原学与治疗及预后的关系

目的 了解北京地区"流感样疾病"的病原谱与抗菌药物治疗及预后的关系.方法 采用前瞻性队列研究方法 ,选取符合卫生部流感样疾病定义的发热门诊患者,留取咽分泌物进行细菌学和病毒学榆测,调查患者的年龄、基础疾病、呼吸道症状、肺外表现和实验室检查,分析治疗和预后的关系.采用SPSS 10.0统计软件进行汇总分析.计量资料采用t榆验或秩和检验,计数资料采用χ2检验,退热时间的影响因素采用Cox回归分析.结果 2006年12月至2007年4月共入选"流感样疾病"患者476例,最终资料完整的454例纳入分析.除副流感嗜血杆菌外,流感病毒是最主要的致病原(197例,43.4%),其他病原体少见.454例患者的平均年龄为(33 ±13)岁,男:女为1.1:1,1年内有流感疫苗接种史的24例(5.3%),接受抗菌约物治疗的288例(63.4%),无接受奥司他韦或金刚烷胺等抗流感病毒药物的患者.与流感病毒阴性组相比,流感病毒阳性组年龄较大、基础疾病较多,咳嗽、咽痛和全身症状的比例较高,但无统计学意义.流感病毒阳性组表现为流感综合征(体温≥39℃,同时伴有咳嗽、咽痛、头痛或全身肌肉酸痛)的比例显著高于流感病毒阴性组.流感病毒阳性组197例中用抗菌药物治疗的132例(67.0%),抗菌药物治疗组外周血白细胞总数、中性粒细胞比例、血小板计数高于未用抗菌药物组;应用抗菌药物组的医疗费用比不用抗菌药物组约高1倍,但平均退热时间、症状缓解时间及复诊率无统计学意义.Cox回归分析结果 显示,白细胞和中性粒细胞百分比增高是退热时间延长的独立危险因素(OR值分别为1.049和1.014),但抗生素使用不影响退热时间.结论 在冬春季节北京地区"流感样疾病"的主要病原体是流感病毒;对于单纯"流感样疾病",抗菌药物治疗不缩短病程,但费用却大大增加.因此,研究并制定流感样疾病诊断和治疗规范非常必要.     

Clinical implications of antibiotic impact on gastrointestinal microbiota and Clostridium difficile infection

The human gastrointestinal (GI) microbiota plays an important role in human health. Anaerobic bacteria prevalent in the normal colon suppress the growth of non-commensal microorganisms, thus maintaining colonic homeostasis. The GI microbiota is influenced by both patient-specific and environmental factors, particularly antibiotics. Antibiotics can alter the native GI microbiota composition, leading to decreased colonization resistance and opportunistic proliferation of non-native organisms. A common and potentially serious antibiotic-induced sequela associated with GI microbiota imbalance is Clostridium difficile infection (CDI), which may become recurrent if dysbiosis persists. This review focuses on the association between antibiotics and CDI, and the antibiotic-induced disruption leading to recurrent CDI. Promoting antibiotic stewardship is pivotal in protecting native microbiota and reducing the incidence of CDI and other GI infections.     

Fidaxomicin: a novel macrocyclic antibiotic approved for treatment of Clostridium difficile infection

Fidaxomicin, a nonabsorbed macrocyclic compound, is the first antimicrobial agent approved by the FDA for the treatment of Clostridium difficile infection (CDI) in adults over the last 25 years. It is bactericidal, and its mechanism of action relates to inhibition of a RNA polymerase at a site distinct from where rifamycins interact. Fidaxomicin, 200?milligrams by mouth twice daily, is not inferior to vancomycin, 125?milligrams by mouth 4 times daily, for treatment of CDI as determined by clinical response after 10 days of treatment and is superior to vancomycin for sustained response without recurrence 25 days after treatment completion. These results are a significant advance in the treatment of CDI and herald the development of narrow-spectrum anti-C. difficile agents that relatively spare the indigenous fecal microbiota. Continued vigilance for the development of resistance and unanticipated side affects will be important as the drug is introduced into clinical practice.     

Differential risks of nosocomial infection

Our ability to interpret apparent differences in findings among surveys of nosocomial infection is limited by differences in the methods used, and differences among the study populations themselves. Methodologic areas in which there are substantial differences include definitions of rates of infection, criteria for infection and methods of case-finding. The studies themselves differ with respect to the characteristics of hospital populations, their underlying diseases, clinical procedures, patterns of lengths of hospital stay and efforts at prevention of infection. There are three separate concerns for constructing and interpreting comparisons: the choice of comparison or reference subjects, the control of confounding variables and the adjustment for variations in hospital stay. In order for studies to be credible, they must be accompanied by convincing evidence that the confounding effects of variables extraneous to the study have been identified and appropriately controlled in the analysis. It has been found that the day-specific incidence of nosocomial infection rises from near zero on the first hospital day to maximal during the fourth through the seventh weeks of hospital stay. Thus, the risk of nosocomial infection for a specific patient also depends on the hospital day. It may be possible to make better use of limited infection control resources by concentrating efforts to prevent infections on the patients who are at greatest risk, during the time when the dayspecific incidence is highest.     

Adverse effects of nosocomial infection

The effects of noscomial infection on duration of hospital stay and outcome of hospitalization were measured by matching two control patients to each of 85 patients found to have qctive nosocomial infection during a prevalence survey at Boston City Hospital in 1973. The control patients were selected from all patients discharged from this hospital during the same time period; they were matched by exact primary discharge diagnosis, similar operative procedure, and age. Patients with a single infection remained in hospital on average 13.0 days longer than their matched controls, and those with two such infections stayed on average 35.4 days longer. This effect of extra stay associated with nosocomial infection was consistent when data were stratified by primary discharge diagnosis, hospital service, site of infection, or outcome of hospitalization. The outcome of hospitalization for these infected patients was slightly, but not significantly, worse than for their matched controls.     

Chronic hepatitis C and Crohn's disease: nosocomial infection treatment with PEG-interferon plus ribavirin

We describe the case of a patient with a diagnosis of Crohn's disease and accidental infection during abdominal surgery by hepatitis C virus (HCV) who received combination therapy with pegylated interferon-alpha2b (1.5 microg/kg weekly) plus ribavirin (10.6 mg/kg daily) for histologically demonstrated chronic hepatitis C. After 48 weeks treatment, serum transaminase levels were normal and viremia (HCV RNA) was negative (end-of-treatment response); 24 weeks later (follow-up period), a sustained virological response was demonstrated. The tolerance to combination antiviral therapy was good, without intestinal symptoms of inflammatory bowel disease recurrence. We conclude that current antiviral therapies with immunomodulatory effects may be helpful and safe for patients with inflammatory bowel disease infected by hepatitis C virus.     

Cost of nosocomial infection: Relative contributions of laboratory,antibiotic, and per diem costs in serious Staphylococcus aureus infections

This study reports an analysis of the relative importance of laboratory antibiotic, and per diem costs of caring for 58 patients with serious Staphylococcus aureus nosocomial infections. Laboratory costs accounted for 2%, antibiotics for 21%, and per diem costs for 77% of total infection-related costs. Only 45% of patients were hospitalized for additional days specifically because of infection, but these patients stayed an average of 18 extra days. Nosocomial infections with S. aureus resistant to penicillinase-resistant penicillins (PRP) were more frequently associated with additional infection-related days of hospitalization than were PRP-susceptible infections. The cost of PRP-resistant infections was also significantly greater than PRP-susceptible infections, primarily because of the costs of additional days of hospitalization. Rational strategies to control costs of nosocomial infection should focus on two approaches: (1) prevention and (2) reduction of acute hospital days attributable to infections.