Uwe Frank

Influence of an Infectious Disease Consulting Service on Quality and Costs of Antibiotic Prescriptions in a University Hospital

An infectious disease consulting service was set up at a large tertiary university hospital in 1996 to evaluate and to improve antibiotic prescription patterns. Treatment guidelines for the most common bacterial infections were implemented. On daily ward rounds antibiotic therapies without evidence of an infectious disease were stopped and inappropriate regimens were changed by an infectious disease specialist. During a 6-month prospective intervention period, 3,528 patients were studied on 13 wards of the department of internal medicine; 513 of these patients (14.5%) received antibiotic therapy. These treatment courses were evaluated as adequate in 394 cases (76.8%) and incorrect in 119 cases (23.2%). Inadequate antibiotic substances were chosen in 72 out of 119 cases (60.5%) and there was no indication for treatment in 38 out of 119 cases (32%). Pathogen-specific therapies were inadequate significantly more often than empirical antimicrobial therapies (p < 0.001). In addition, the duration of the perioperative prophylaxis could be limited to 1 d. Comparing the intervention period with a 3-month control interval without an infectious disease consulting service, a total of 31,510 Euro (including the costs for the infectious disease specialist) could be saved. No increase in infection-related mortality or length of stay was observed. These data show that an infectious disease consulting service optimizes antibiotic usage, and is cost-effective as a result of a significant cost reduction in hospitals, while not interfering with the quality of medical care.An infectious disease consulting service was set up at a large tertiary university hospital in 1996 to evaluate and to improve antibiotic prescription patterns. Treatment guidelines for the most common bacterial infections were implemented. On daily ward rounds antibiotic therapies without evidence of an infectious disease were stopped and inappropriate regimens were changed by an infectious disease specialist. During a 6-month prospective intervention period, 3,528 patients were studied on 13 wards of the department of internal medicine; 513 of these patients (14.5%) received antibiotic therapy. These treatment courses were evaluated as adequate in 394 cases (76.8%) and incorrect in 119 cases (23.2%). Inadequate antibiotic substances were chosen in 72 out of 119 cases (60.5%) and there was no indication for treatment in 38 out of 119 cases (32%). Pathogen-specific therapies were inadequate significantly more often than empirical antimicrobial therapies (p < 0.001). In addition, the duration of the perioperative prophylaxis could be limited to 1 d. Comparing the intervention period with a 3-month control interval without an infectious disease consulting service, a total of 31,510 Euro (including the costs for the infectious disease specialist) could be saved. No increase in infection-related mortality or length of stay was observed. These data show that an infectious disease consulting service optimizes antibiotic usage, and is cost-effective as a result of a significant cost reduction in hospitals, while not interfering with the quality of medical care.

Effect of skin disinfection with octenidine dihydrochloride on insertion site colonization of intravascular catheters.

Abstract.Background: We investigated the efficacy of two commercially available, alcohol-based antiseptic solutions in decontaminating the insertion site of central lines. One solution contained the bispyridine octenidine dihydrochloride.nPatients and Methods: Inpatients receiving either a central venous catheter (CVC) or a peripherally inserted central catheter (PICC) were alternately assigned to different skin disinfection regimens at the insertion site: (A) 0.1% octendine dihydrochloride with 30% 1-propanol and 45% 2-propanol, (B) 74% ethanol with 10% 2-propanol. Quantitative skin cultures were obtained from the insertion site at predetermined intervals.nResults: A total of 60 patients received 12 CVCs and 47 PICCs (no significant difference with respect to gender, age and catheter type). In total, 90 cultures were assessed in each group. The median colony-forming unit (cfu) counts per 24 cm2 (group A vs B) were 2,270 vs 2,950 before, 20 vs 40 following and 860 vs 1,210 24 h after catheter insertion, respectively. A statistically significant difference in the efficacy of skin decontamination was seen between groups in culture set (3) and in the difference between culture sets (2) and (3) (Wilcoxon rank sum test).nConclusion: Octenidine/propanol appears to be more effective than alcohol (ethanol/propanol) alone in reducing microflora of the skin at the PICC/CVC insertion site over a 24-h period.

Incidence and epidemiology of nosocomial infections in patients infected with human immunodeficiency virus

In a prospective study, we investigated the incidence, characteristics, and risk factors of nosocomial infections (NIs) in patients with human immunodeficiency virus disease. There was a total of 528 admissions of 405 eligible patients; 46 NIs (8.7% per discharge) were identified in 39 patients. The proportional frequencies of NIs were as follows: 16 skin and/or soft-tissue infections (including localized catheter-associated infections), 3.0%; 14 respiratory tract infections, 2.7%; 11 bloodstream infections, 2.1%; and 5 urinary tract infections, 0.9%. The most common etiologic agents were Staphylococcus aureus (27.6%), Pseudomonas aeruginosa (13.8%), and Enterobacter cloacae (13.8%). The duration of hospitalization was not significantly prolonged by NI in the cohort.

Control of the Spread of Vancomycin-Resistant Enterococci in Hospitals: Epidemiology and Clinical Relevance

BACKGROUNDnThe spread of vancomycin-resistant enterococci (VRE), particularly E. faecium, in hospitals leads to many cases of colonization, but only sporadic infections. Detailed and valid risk assessment is needed so that patients at risk can be protected from VRE infection. The principal aims of risk assessment must include not only lowering VRE-associated morbidity and mortality in patients at risk, but also refraining from unnecessary anti-infective measures among those who are not at risk.nnnMETHODSnWe selectively searched the PubMed database for pertinent articles on the epidemiology and clinical relevance of VRE in order to derive a uniform and practical hygiene strategy from the available scientific evidence.nnnRESULTSnOnly low-level evidence is available for the interventions studied to date, and most of the recommendations that have been issued can be characterized as expert opinion. As a rule, VRE are not highly pathogenic; they tend to have high rates of colonization, but low rates of infection. The risk factors for colonization with VRE include (among others) the administration of antibiotics and immunosuppressants, prior hospitalization, diarrhea, intubation, and other invasive treatments. The areas of highest risk are hematology/oncology wards, liver transplantation wards, dialysis units, and neonatology wards.nnnCONCLUSIONnThe chain of infection can be broken by improved and consistently applied standard hygienic measures (hand and surface disinfection). Some patients are nonetheless at elevated risk of VRE infection. In specific clinical situations, the optimal protection of these patients against VRE infection demands the obligatory enforcement of stricter hygienic measures (contact isolation).

The need for macrolides in hospitalised community-acquired pneumonia: propensity analysis

The present study compared β-lactam macrolide (“combination”) therapy versus β-lactam alone (“monotherapy”) for hospitalised community-acquired pneumonia, using propensity scores to adjust for the differences between patients. A prospective multinational observational study was carried out. Baseline patient and infection characteristics were used to develop a propensity score for combination therapy. Patients were matched by the propensity score (three decimal point precision) and compared with 30-day mortality and hospital stay. The propensity score was used as a covariate in a logistic model for mortality. Patients treated with monotherapy (nu200a=u200a169) were older (mean±sd age 70.6±17.3 versus 65.0±19.6u2005yrs), had a higher chronic diseases score and a different clinical presentation compared with patients treated with combination therapy (nu200a=u200a282). Unadjusted mortality was significantly higher with monotherapy (37 (22%) out of 169 versus 21 (7%) out of 282). Only 27 patients in the monotherapy group could be matched to 27 patients in the combination group using the propensity score. The mortality in these groups was identical, with three (11%) demises each. The multivariable odds ratio for mortality associated with combination therapy, adjusted for the propensity score and the Pneumonia Severity Index, was 0.69 (95% confidence interval 0.32–1.48). The benefit of combination therapy versus monotherapy cannot be reliably assessed in observational studies, since the propensity to prescribe these regimens differs markedly.

The pathogenetic significance of intestinal Candida colonization--a systematic review from an interdisciplinary and environmental medical point of view.

The etiological significance of intestinal Candida colonization continues to be controversial. This is a systematic review to determine the pathogenetic significance of intestinal Candida colonization. The search was essentially performed from 1990 to 12/7/2000 in Medline and the Cochrane-Library. The data source was restricted to articles in English and German. Selection criteria covered the topics Epidemiology, Infectious Diseases, Candida-Syndrome and Therapy and were essentially confined to in-vivo examination of immunocompetent adults. Two reviewers extracted independently data using predefined criteria. In total, 96 citations that proved suitable for use in the systematic review were found. Depending on the localization in the gastrointestinal tract, the recovery technique employed, and transport times, Candida colonization is frequently detected in healthy, immunocompetent adults (prevalence: 4-88%). None of the studies available so far furnish any evidence that nutritional factors, food additives, pollutants, anti-ovulants, other types of medication or diabetes mellitus might be predisposing factors for intestinal Candida colonization. However, therapeutic studies point to the possibility of Candida playing a role in antibiotic-associated diarrhea. On the other hand, antibiotics seem to favor bacterial dysbiosis, and this, like the direct side effects of drugs, offers a more plausible explanation for diarrhea or gastrointestinal symptoms. The role of intestinal colonization by Candida in Candida-associated vulvovaginitis and IgE-mediated disorders remains contradictory. Nevertheless, neither epidemiological nor therapeutic studies provide evidence for the existence of the so-called Candida-syndrome or Candida-hypersensitivity-syndrome. At present, there are no proven treatment indications for antifungal bowel decontamination.

Ceftriaxone versus Other Cephalosporins for Perioperative Antibiotic Prophylaxis: A Meta-Analysis of 43 Randomized Controlled Trials

The efficacy of ceftriaxone versus other cephalosporins in the perioperative prophylaxis of surgical wound, urinary tract and respiratory tract infections was compared in a meta-analysis of randomized controlled trials published between 1986 and 1996, identified from the Medline, Embase, SIGLE, ROPU, DHSS-Data and Medikat Cologne databases. Studies were grouped by type of infection, operative specialty, wound classification, study quality and other factors, and assessed for relative risk (RR). Forty-three studies with a total of 13,482 patients met our inclusion criteria. RR for surgical wound infection (n = 13,303 patients) was 30% lower in the ceftriaxone versus control groups [98.3% confidence interval (CI): 0.55–0.89; p = 0.0002]. In urinary tract infections (n = 8,865 patients), the primary analysis of all studies showed marked superiority for ceftriaxone (RR: 0.53; 98.3% CI: 0.43–0.67) but not in studies with CDC-defined infections (RR: 0.63; 98.3% CI: 0.36–1.12). In both types of infection, ceftriaxone was superior in contaminated operations. The data showed no advantage for ceftriaxone in other operations. In respiratory tract infections (n = 9,567 patients), there was no significant difference: the RR was 0.81 (98.3% CI: 0.61–1.09; p = 0.04).

Multicentre study of antimicrobial resistance and antibiotic consumption among 6,780 patients with bloodstream infections.

Several lines of evidence suggest there is a causal association between the use of antimicrobial agents and the prevalence of antimicrobial resistance in hospitalacquired bacterial pathogens [1, 2]. However, recently published works have indicated the magnitude of the association may be lower than that previously observed and that many other variables, such as patient factors may be responsible for the development of antimicrobial resistance [3, 4]. The specific goals of this study were (1) to estimate antimicrobial resistance rates for four epidemiologically important pathogens causing bloodstream infections (BSI), (2) to compare the antimicrobial resistance rates with the hospital’s antibiotic consumption data, and (3) to determine a possible relationship between the use of antimicrobial agents and the prevalence of drug resistance in these microorganisms. The participating hospitals were partners in the TREAT project, financed by the European Community (EC, 5th Framework, 1999) and focusing on the application of an electronic decision support system to reduce antimicrobial resistance in hospitalised patients [5] This multicentre study was conducted at Freiburg University Hospital, Freiburg, Germany; Rabin Medical Center, Tel Aviv (Petah Tiqva), Israel; Aalborg Hospital, Aalborg, Denmark; and Catholic University Hospital, Rome, Italy. Data on consumption of antibiotics (from 1998 to 2001) were supplied by the hospital pharmacies and expressed in daily defined doses (DDD) per 1,000 bed-days, as outlined by the World Health Organisation. Data on consumption of the following drugs were provided (if included in the local formulary): clindamycin, trimethoprim-sulfamethoxazole, imipenem, ampicillin, ceftazidime, cefepime, piperacillin, piperacillin-tazobactam, and gentamicin. We prospectively included, from 1998 to 2001, all consecutive non-repeat blood isolates of patients with nosocomial BSI according to the definition given by the Centers for Disease Control and Prevention (Atlanta, GA, USA). Mixed cultures were excluded. Selected isolates from patients with bacteraemia included Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Microorganisms were identified using standard methods. Trends in resistance and the possible correlation between resistance and consumption were analysed using the logit regression line. Antimicrobial consumption patterns varied widely at the four sites. The most frequently prescribed drugs (>40 DDD per 1,000 bed-days) were ampicillin and gentamicin in Denmark and Israel and ceftazidime in Germany and Italy. Eur J Clin Microbiol Infect Dis (2006) 25:815–817 DOI 10.1007/s10096-006-0211-2

In vitro activity of sulbactam plus ampicillin against hospital isolates of coagulase-negative staphylococci and Acinetobacter species.

SummaryThe antimicrobial susceptibility of 54 recent clinical isolates of coagulase-negative slime- and non-slime-producing staphylococci and 52Acinetobacter spp. to sulbactam, ampicillin and the combination of both drugs with a 1:1 ratio was studied by means of an agar dilution test. The coagulase-negative staphylococci showed resistance against sulbactam alone, whereas ampicillin as a single agent was nearly as active as sulbactam plus ampicillin (mode of MIC and MBC 0.03 and 4 mg/l vs. 1 mg/l; geometric mean of MIC and MBC 0.38 and 0.56 vs. 0.26 and 0.38 mg/l, respectively). Among slime-producing or non-slime-producing strains, there was no difference in the susceptibility against ampicillin alone compared to the sulbactam/ampicillin combination, with the exception of the higher MBC (mode: 4 mg/l) for slime-producing strains. Both ampicillin and the sulbactam/ampicillin combination were more active against non-slime-producing than slime-producing strains with modes of MIC and MBC of 0.03 vs. 1 or 4 mg/l.Acinetobacter spp. were susceptible to sulbactam alone (mode of MIC and MBC 1 mg/l; geometric mean of MIC and MBC 1.51 and 2.98, respectively), but resistant to ampicillin. However, the sulbactam/ampicillin combination was highly active againstAcinetobacter spp. (mode of MIC and MBC 0.5 and 2 mg/l; geometric mean of MIC and MBC 0.74 and 2.08 mg/l, respectively).ZusammenfassungBei klinischen Isolaten von 54 koagulase-negativen schleimbildenden und nicht-schleimbildenden Staphylokokken und 52 Acinetobacter-Spezies wurde im Agardilutionstest das Resistenzverhalten gegenüber Sulbactam, Ampicillin und der 1:1-Kombination aus beiden Substanzen untersucht. Die koagulase-negativen Staphylokokken erwiesen sich als sulbactam-resistent, jedoch gleichsam ampicillin- wie sulbactam/ampicillin-empfindlich (MHK- bzw. MBK-Modalwert Ampicillin: 0,03 bzw. 4 mg/l; Sulbactam/Ampicillin: jeweils 1 mg/l; geometrischer MHK- bzw. MBK-Mittelwert Ampicillin: 0,38 bzw. 0,56 mg/l, Sulbactam/Ampicillin: 0,26 bzw. 0,38 mg/l). In der Empfindlichkeit schleimbildender oder nicht-schleimbildender Stämme bestand gegen Ampicillin im Vergleich zur Kombination kein Unterschied; eine Ausnahme hiervon machte nur die höhere Ampicillin-MBK (Modalwert: 4 mg/l) gegen die schleimbildenen Stämme. Ampicillin sowie Sulbactam/Ampicillin zeigten größere Wirksamkeit gegen nichtschleimbildende als gegen schleimbildende Stämme mit MHK- bzw. MBK-Modalwerten von 0,03 vs 1 mg/l. Acinetobacter-Spezies waren sulbactam-empfindlich (MHK- bzw. MBK-Modalwert 1 mg/l; geometrischer MHK- bzw. MBK-Mittelwert 1,51 bzw. 2,98 mg/l), jedoch ampicillin-resistent. Die Kombination Sulbactam/Ampicillin dagegen zeigte eine sehr gute Wirksamkeit gegen die Keime aus der Acinetobacter-Gruppe (MHK-bzw. MBK-Modalwert 0,5 bzw. 2 mg/l; geometrischer MHK- bzw. MBK-Mittelwert 0,74 bzw. 2,08 mg/l).

Concentrations of sulbactam/ampicillin in serum and lung tissue

SummaryThe penetration of sulbactam plus ampicillin into lung tissue was studied in 15 patients undergoing thoracic surgery for pneumonectomy after the administration of 1 g of sulbactam plus 2 g of ampicillin as a 15 min intravenous short infusion. Ampicillin serum concentrations declined from 40.8 mg/l at 1 h to 18.8 mg/l 2–4 h after administration. Concomitant serum concentrations of sulbactam were 25.5 mg/l and 11.8 mg/l, respectively. In lung tissue, peak ampicillin concentrations of 35.6 mg/kg were reached 1.5 h after administration declining slowly to 26.8 mg/kg after 2–4 h. The respective sulbactam concentrations were 8.6 and 5.5 mg/kg. In our study sufficient sulbactam and ampicillin levels active against important pathogenic organisms causing community-and hospital-acquired respiratory tract infections have been achieved in lung tissue, suggesting that the combination sulbactam/ampicillin is suited for the treatment of most community- and hospital-acquired respiratory tract infections as well as for chemoprophylaxis and treatment of postoperative lung infections after thoracic surgery.ZusammenfassungDie Antibiotika-Wirkstoffkonzentrationen von Sulbactam/Ampicillin in Lungengewebe wurden bei 15 lungenchirurgischen Patienten untersucht, denen präoperativ vor Pneumonektomie eine i. v. Kurzinfusion von 1 g Sulbactam plus 2 g Ampicillin verabreicht wurde. Die Serumkonzentration von Ampicillin betrug 1 Stunde nach Antibiotikagabe 40,8 mg/l und fiel nach 2–4 Stunden auf 18,8 mg/l ab. Die entsprechenden Serumkonzentrationen von Sulbactam betrugen 25,5 mg/l nach 1 Stunde und 11,8 mg/l nach 2–4 Stunden. Der Spitzenspiegel von Ampicillin in Lungengewebe wurde nach 1,5 Stunden bestimmt und betrug 35,6 mg/kg; nach 2–4 Stunden wurden noch 26,8 mg/kg gemessen. Die Lungengewebespiegel von Sulbactam sanken von 8,6 mg/kg nach 1 Stunde auf 5,5 mg/kg nach 2–4 Stunden. Die gemessenen Wirkstoffkonzentrationen von Sulbactam und Ampicillin waren ausreichend, um die wichtigsten Erreger ambulant- und krankenhaus-erworbener Atemwegsinfektionen zu hemmen. Die Kombination Sulbactam/Ampicillin ist daher geeignet für die Behandlung ambulanter und nosokomialer Atemwegsinfektionen sowie für die Antibiotikaprophylaxe und Behandlung von postoperativen Lungeninfektionen nach thoraxchirurgischen Eingriffen.