Biomedical subjects
Publications and source records attributed to Stephan Harbarth.
At the beginning of the 21st century, antimicrobial resistance is common, has developed against every class of antimicrobial drug, and appears to be spreading into new clinical niches. We describe determinants likely to influence the future epidemiology and health impact of antimicrobial-resistant infections. Understanding these factors will ultimately optimize preventive strategies for an unpredictable future.
An elderly patient dies from septic shock in the intensive care unit. This is perhaps not an unusual scenario, but in this case the sepsis happens to have been due to methicillin-resistant Staphylococcus aureus, possibly related to a catheter, and possibly transmitted from a patient in a neighbouring room by less than adequate compliance with infection control procedures. The family decides to sue. We present how experts from four different countries assess the medicolegal issues involved in this case.
INTRODUCTION: Bacterial infection represents a serious risk in neonates and critically ill paediatric patients. Current clinical practice is characterized by frequent antibiotic treatment despite low incidence of true infection. However, some patients escape early diagnosis and progress to septic shock. Many new markers, including cytokines, have been suggested to improve decision making, but the clinical efficacy of these techniques remains uncertain. Therefore, we will test the clinical efficacy of a previously validated diagnostic strategy to reduce antibiotic usage and nosocomial infection related morbidity. METHODS: All patients admitted to the multidisciplinary neonatal and paediatric intensive care unit of a university children's hospital will be included. Patients will be allocated either to routine sepsis work up or to the intervention strategy with additional cytokine measurements. Physicians will be requested to estimate the pre-test probability of sepsis and pneumonia at initial suspicion. In the treatment arm, physicians will receive raw cytokine results, the likelihood ratio and the updated post-test probability. A high post-test probability will suggest that immediate initiation of antibiotic treatment is appropriate, whereas a low post-test probability will be supportive of watchful waiting or discontinuing prophylactic empirical therapy. Physicians may overrule the suggestions resulting from the post-test probability. CONCLUSION: This trial will ascertain the clinical efficacy of introducing new diagnostic strategies consisting of pre-test probability estimate, novel laboratory markers, and computer-generated post-test probability in infectious disease work up in critically ill newborns and children.
BACKGROUND: Oral combination therapy with fluoroquinolones plus rifampicin is a promising alternative to standard parenteral therapy for staphylococcal infections. METHODS: In a multicenter, randomized trial, we compared the efficacy, safety, and length of hospital stay for patients with staphylococcal infections treated either with an oral combination of a fluoroquinolone (fleroxacin) plus rifampicin or with standard parenteral treatment (flucloxacillin or vancomycin). Patients were included if cultures showed the presence of bacteremia or deep-seated infections with Staphylococcus aureus (104 patients) or catheter-related bacteremia due to drug-susceptible, coagulase-negative staphylococci (23 patients). RESULTS: The cure rate in the intention-to-treat analysis was 78% for the fleroxacin-rifampicin group (68 patients) and 75% for the standard therapy group (59 patients; 47 received flucloxacillin, and 12 received vancomycin); in the population of clinically evaluable patients (n=119), the cure rate was 82% and 80%, respectively; and in the population of microbiologically evaluable patients (n=103), the cure rate was 86% and 84%, respectively. Clinical and bacteriological failures after S. aureus infections were documented in similar proportions of patients. The median length of hospital stay after study entry was 12 days in the fleroxacin-rifampicin group, compared with 23 days in the standard treatment group (P=.006). More adverse events probably related to the study drug were reported in the fleroxacin-rifampicin group than in the standard therapy group (15 of 68 vs. 5 of 59 patients; P=.05). CONCLUSIONS: This study suggests that an oral regimen containing a fluoroquinolone plus rifampicin may be effective for treating staphylococcal infections, allowing earlier discharge from the hospital.
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To determine the diagnostic accuracy of physicians' prior probability estimates of serious infection in critically ill neonates and children, we conducted a prospective cohort study in 2 intensive care units. Using available clinical, laboratory, and radiographic information, 27 physicians provided 2567 probability estimates for 347 patients (follow-up rate, 92%). The median probability estimate of infection increased from 0% (i.e., no antibiotic treatment or diagnostic work-up for sepsis), to 2% on the day preceding initiation of antibiotic therapy, to 20% at initiation of antibiotic treatment (P<.001). At initiation of treatment, predictions discriminated well between episodes subsequently classified as proven infection and episodes ultimately judged unlikely to be infection (area under the curve, 0.88). Physicians also showed a good ability to predict blood culture-positive sepsis (area under the curve, 0.77). Treatment and testing thresholds were derived from the provided predictions and treatment rates. Physicians' prognoses regarding the presence of serious infection were remarkably precise. Studies investigating the value of new tests for diagnosis of sepsis should establish that they add incremental value to physicians' judgment.
The Programme for International Student Assessment (PISA) 2000 study assessed a wide range of knowledge and skills attained by 265,000 15-year-olds in 32 industrialized countries. One survey unit of the scientific literacy section addressed infection control issues, based on Semmelweis' landmark research on the causes and prevention of puerperal fever. The present report describes the questions and student performance for this infection control exercise set and evaluates performance variability between countries.
OBJECTIVES: To investigate an outbreak of Pseudomonas aeruginosa pneumonia and bloodstream infection among four neonates, determine risk factors for infection, and implement preventive strategies. DESIGN: Retrospective case finding; prospective surveillance cultures of patients, personnel, and environmental sites; molecular typing by pulsed-field gel electrophoresis; and a matched case-control study. PATIENTS AND SETTING: Neonates in the level-III neonatal intensive care unit of a tertiary-care pediatric institution. INTERVENTIONS: Cohorting of patients with positive results for P. aeruginosa, work restrictions for staff with positive results, implementation of an alcohol-based hand product, review of infection control policies and procedures, and closure of the unit until completion of the investigation. RESULTS: Seven (4%) of 190 environmental cultures and 5 (3%) of 178 cultures of individual healthcare workers' hands grew P. aeruginosa. All four outbreak isolates and one previous bloodstream isolate were genotypically identical, as were the P. aeruginosa isolates from the hands and external auditory canal of a healthcare worker with intermittent otitis externa. Four of 5 case-patients versus 5 of 15 matched control-patients had been cared for by this healthcare worker (P = .05). The healthcare worker was treated and no further cases occurred. CONCLUSIONS: These findings suggest that a healthcare worker with intermittent otitis externa may have caused this cluster of fatal P. aeruginosa infections, adding the external ear to the list of colonized body sites that may serve as a source of potentially pathogenic organisms.
We evaluated the costs associated with a sustained and successful campaign for hand hygiene promotion that emphasized alcohol-based handrubs. The total cost of the hand hygiene promotion corresponded to less than 1% of the costs associated with nosocomial infections. Successful hand hygiene promotion is probably cost-saving.
OBJECTIVE: Examine whether a low serum level of apolipoprotein A-I at intensive care unit (ICU) admission is associated with a further increase of the number of systemic inflammatory response syndrome (SIRS) criteria. DESIGN: Prospective observational study. SETTING: A 20-bed, university-affiliated, surgical ICU. PATIENTS: Patients admitted after major surgery, multiple trauma, or acute pancreatitis without septic shock. INTERVENTIONS: We defined as the SIRS Exacerb group patients who presented a further increase of the number of SIRS criteria during their ICU stay or, in the presence of four SIRS criteria at ICU admission, those who presented a further aggravation of organ failure. Other patients were attributed to the SIRS No Exacerb group. From day 1 to 6, we measured apolipoprotein A-I, high-density lipoprotein and total cholesterol, triglycerides, C-reactive protein, procalcitonin, serum amyloid A, interleukin 6, interleukin-1 receptor antagonist, albumin, and other nutrition-linked variables. We looked at laboratory values or factors present at ICU admission according to the two groups. MEASUREMENTS AND MAIN RESULTS: From 63 patients analyzed, 29 (46%) were assigned to the SIRS Exacerb group. Age, sex, and SAPS II and SIRS scores at ICU admission did not differ between the groups. Patients in the SIRS Exacerb group presented more often a septic event (5/29 vs. 0/34, p =.02), had a higher hospital mortality (6/29 vs. 0/34, p =.007), and had a longer ICU stay (p =.0023). At admission, inflammatory variables such as the C-reactive protein, serum amyloid A, interleukin 6, interleukin-1 receptor antagonist plasma levels, and other lipid or nutrition-linked variables were similar between the two groups. Apolipoprotein A-I levels were lower in the SIRS Exacerb group (median [interquartile range]: 68 [56-81] vs. 84 [69-94] mg/dL, p =.028). CONCLUSION: A low serum level of apolipoprotein A-I at ICU admission is associated with an increase of the number of SIRS criteria during the ICU stay.
PURPOSE OF REVIEW: There is growing concern that changes in nurse workforce and hospital-restructuring interventions negatively impact on patient outcomes. This review focuses on the association between understaffing and health-care-associated infections. RECENT FINDINGS: There is a large number of studies showing that overcrowding, understaffing or a misbalance between workload and resources are important determinants of nosocomial infections and cross-transmission of microorganisms. Importantly, not only the number of staff but also the level of their training affects outcomes. The nurse workforce is ageing, mainly due to fewer individuals' engaging in a nursing career. This phenomenon, combined with cost-driven downsizing, contributes to a nursing shortage, and this tendency is not expected to revert unless important system changes are implemented. The causal pathway between understaffing and infection is complex, and factors might include lack of time to comply with infection control recommendations, job dissatisfaction, job-related burnout, absenteeism and a high staff turnover. SUMMARY: The evidence that cost-driven downsizing and changes in staffing patterns causes harm to patients cannot be ignored, and should not be considered as an inevitable outcome. More research is needed to better define the optimal patient-to-nurse ratio in various hospital settings and to estimate the economical impact of the nursing shortage. All quality-improvement interventions should carefully take into account systems and processes to be successful, as the issue of staffing is essentially a structural problem.
OBJECTIVES: To assess the effect of a comprehensive, educational antibiotic management program designed to improve antibiotic use and reduce treatment costs in elderly patients with suspected urinary or respiratory tract infection. DESIGN: Interventional cohort study with 12 cross-sectional drug utilization reviews of antibiotic use before, during, and after the multifaceted intervention. SETTING: A 304-bed university hospital for geriatric patients. PARTICIPANTS: A total of 3,383 elderly patients. INTERVENTIONS: An educational program including distribution of guidelines on the diagnosis and treatment of urinary and respiratory tract infections; lectures on geriatric infectious diseases; weekly ward rounds for patients with suspected infection; and targeted, individual counseling on diagnosis and antibiotic treatment of infections. MEASUREMENTS: Antibiotic utilization data were collected from the patients' records. Antimicrobial costs were calculated using 1998 hospital wholesale prices. RESULTS: Of 3,383 screened patients, 680 (20%) received at least one antibiotic. During the study period, the mean number of prescribed drugs per patient increased from 5.9 to 7.6 (29%; P<.001). In contrast, a reduction of 15% was observed in the proportion of patients exposed to antibiotic agents (P=.08) and a drop of 26% in the number of antibiotics administered (P<.001). This resulted in a 54% decrease in cumulative daily antibiotic costs. In 83 (75%) of 110 surveyed patients, the guidelines were correctly implemented. The intervention had no measurable negative clinical effect. CONCLUSION: A comprehensive, multifaceted educational program for treating urinary and respiratory tract infections in the elderly was a safe and practical method to change physicians' antibiotic prescribing practice and significantly reduce the consumption and costs of antibiotics in a geriatric hospital.
We describe a novel procedure for rapid typing of the staphylococcal cassette chromosome mec element, a molecular marker allowing discrimination between community- and hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) strains. Oligonucleotides targeting the recombinase genes were type specific and used to type a collection of 399 MRSA isolates recovered during patient screening at admission. This novel assay constitutes a valuable tool for evaluating the molecular epidemiology of MRSA and adjusting infection control strategies against MRSA.
We correlated outpatient antibiotic use with prevalence of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP), macrolide-resistant S. pneumoniae (MRSP), and macrolide-resistant S. pyogenes (MRGAS) in 20 countries. Total antibiotic use was correlated with PNSP (r = 0.75; p < 0.001), as was macrolide use with MRSP (r = 0.88; p < 0.001) and MRGAS (r = 0.71; p = 0.004). Streptococcal resistance is directly associated with antibiotic selection pressure on a national level.
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To determine whether acute respiratory distress syndrome (ARDS) complicating bacteremic sepsis independently affects mortality in critically ill patients, we conducted a 3-year retrospective cohort study in a surgical intensive care unit. We included all consecutive patients with blood culture-positive sepsis and measured organ dysfunctions and mortality. Among 4,530 admissions, 196 cases of bacteremic sepsis were recorded. ARDS occurred in 31 (16%) of these patients. The case fatality rate was 58% in patients with ARDS compared with 31% in patients without ARDS. Using Cox proportional hazards regression with time-dependent variables, the unadjusted hazard ratio for death was 1.8 (95% confidence interval [CI], 1.0-3.2). After adjusting for comorbid factors that were present before the onset of sepsis, the hazard ratio was 2.2 (95% CI, 1.2-3.9). After further adjustment was made for nonpulmonary organ dysfunctions and microbiologic factors that were independently associated with mortality, the adjusted hazard ratio for ARDS was 0.6 (95% CI, 0.3-1.2). Among critically ill surgical patients, ARDS complicating bacteremic sepsis remains common, but it is not independently associated with short-term mortality, after adjusting for severity of illness and nonpulmonary organ dysfunctions evolving after the onset of sepsis.
PURPOSE: To examine the effect of inappropriate initial antimicrobial therapy on the prognosis of patients with sepsis who were enrolled in a clinical trial of an immunomodulating agent conducted in 108 hospitals in North America and Europe. METHODS: We assessed initial antimicrobial choice and results of microbiologic cultures in 904 patients who had microbiologically confirmed severe sepsis or early septic shock. If a patient did not receive at least one antimicrobial agent to which the causative microorganisms were susceptible within 24 hours from the diagnosis of severe sepsis, then the initial antimicrobial treatment was considered to be inappropriate. A propensity score that adjusted for factors associated with inappropriate antimicrobial treatment was calculated and included in multivariable models to adjust for confounding. RESULTS: A total of 468 patients (52%) had documented bloodstream infection, and 211 patients (23%) received inappropriate initial antimicrobial therapy. Characteristics associated with inappropriate treatment were study enrollment in Europe, admission to surgery, nosocomial infection, infection with multiresistant microorganisms, and fungal or polymicrobial infection (all P <0.05). The 28-day mortality was 24% (168/693) for patients in the adequately treated group versus 39% (82/211) for patients receiving inappropriate initial antimicrobial therapy (P <0.001). After adjusting for comorbid conditions, severity of illness, site of infection, and the propensity score, inappropriate antimicrobial therapy was independently associated with increased mortality (odds ratio = 1.8; 95% confidence interval: 1.2 to 2.6). CONCLUSION: In a large cohort of patients with microbiologically confirmed severe sepsis, appropriate initial antimicrobial therapy was an important determinant of survival. New approaches aimed at improving detection and treatment of early sepsis are needed.
A six-year retrospective study was undertaken to examine the effect of the recent penicillin G (penG) shortage on antibiotic prescribing practices at a tertiary care centre in the US. Prior to the shortage, penG was predominantly used for intrapartum prophylaxis of group B streptococcal disease. As the supply of penG ended temporarily in October 1999, penG use declined dramatically, ampicillin replaced penG in obstetrics and a shift to broad-spectrum agents was noted in non-obstetric patients potentially eligible for penG treatment. Shortage-triggered treatment changes had a negative effect on prescribing patterns, which may contribute to antibiotic resistance.