Nosocomial influenza in south-western Swiss hospitals during two seasonal epidemics: an observational study.

BACKGROUND: In Switzerland each year, influenza leads to between 112,000 and 275,000 medical consultations. Data on nosocomial influenza infection are limited. AIM: To describe nosocomial cases of seasonal influenza in south-western Switzerland. METHODS: This study was conducted during two seasonal influenza epidemics from 2016 to 2018 in 27 acute care public hospitals in south-western Switzerland. During these two time-periods, every patient hospitalized for >72 h who was positively screened by reverse transcription-polymerase chain reaction or antigen detection for influenza was included in the survey. Characteristics of patients included age, sex, and comorbidities. Included patients were followed up until discharge or death. Complications and administration of antineuraminidases and/or antibiotics were registered. FINDINGS: The median influenza vaccine coverage of healthcare workers was 40%. In all, 836 patients were included (98% with type A influenza virus in 2016-2017; 77% with type B virus in 2017-2018). Most patients (81%) had an unknown vaccine status. Overall, the incidence of nosocomial influenza was 0.5 per 100 admissions (0.35 per 1000 patient-days). The most frequent comorbidities were diabetes (20%), chronic respiratory diseases (19%), and malnutrition (17%). Fever (77%) and cough (66%) were the most frequent symptoms. Seventy-one percent of patients received antineuraminidases, 28% received antibiotics. Infectious complications such as pneumonia were reported in 9%. Overall, the all-cause mortality was 6%. CONCLUSION: The occurrence of nosocomial influenza underlines the importance of vaccinating patients and healthcare workers, rapidly recognizing community- or hospital-acquired cases, and applying adequate additional measures to prevent dissemination, including the timely administration of antineuraminidases to avoid antibiotic use (and misuse).

CSF lactate for accurate diagnosis of community-acquired bacterial meningitis.

CSF lactate measurement is recommended when nosocomial meningitis is suspected, but its value in community-acquired bacterial meningitis is controversial. We evaluated the diagnostic performance of lactate and other CSF parameters in a prospective cohort of adult patients with acute meningitis. Diagnostic accuracy of lactate and other CSF parameters in patients with microbiologically documented episodes was assessed by receiver operating characteristic (ROC) curves. The cut-offs with the best diagnostic performance were determined. Forty-five of 61 patients (74%) had a documented bacterial (n = 18; S. pneumoniae, 11; N. meningitidis, 5; other, 2) or viral (n = 27 enterovirus, 21; VZV, 3; other, 3) etiology. CSF parameters were significantly different in bacterial vs. viral meningitis, respectively (p < 0.001 for all comparisons): white cell count (median 1333 vs. 143/mm(3)), proteins (median 4115 vs. 829 mg/l), CSF/blood glucose ratio (median 0.1 vs. 0.52), lactate (median 13 vs. 2.3 mmol/l). ROC curve analysis showed that CSF lactate had the highest accuracy for discriminating bacterial from viral meningitis, with a cutoff set at 3.5 mmol/l providing 100% sensitivity, specificity, PPV, NPV, and efficiency. CSF lactate had the best accuracy for discriminating bacterial from viral meningitis and should be included in the initial diagnostic workup of this condition.

[Prosthetic hip infection due to Listeria monocytogenes: review of the literature and case report]. / Infection prothétique de hanche à Listeria monocytogenes.

With the ageing of the population, articular prosthetic replacements are becoming more and more frequent. One of the most feared complications is prosthetic infection, mostly due to bacteria of the cutaneous flora. Listeria monocytogenes is rarely the cause. This paper describes the management of a hip prosthetic infection due to Listeria monocytogenes. The patient was cured with antimicrobial therapy and a two-stage exchange. This case report creates an opportunity to review the literature in the aim of determining the risk factors and the optimal care.

Investigation of classical epidemiological links between patients harbouring identical, non-predominant meticillin-resistant Staphylococcus aureus genotypes and lessons for epidemiological tracking.

According to molecular epidemiology theory, two isolates belong to the same chain of transmission if they are similar according to a highly discriminatory molecular typing method. This has been demonstrated in outbreaks, but is rarely studied in endemic situations. Person-to-person transmission cannot be established when isolates of meticillin-resistant Staphylococcus aureus (MRSA) belong to endemically predominant genotypes. By contrast, isolates of infrequent genotypes might be more suitable for epidemiological tracking. The objective of the present study was to determine, in newly identified patients harbouring non-predominant MRSA genotypes, whether putative epidemiological links inferred from molecular typing could replace classical epidemiology in the context of a regional surveillance programme. MRSA genotypes were defined using double-locus sequence typing (DLST) combining clfB and spa genes. A total of 1,268 non-repetitive MRSA isolates recovered between 2005 and 2006 in Western Switzerland were typed: 897 isolates (71%) belonged to four predominant genotypes, 231 (18%) to 55 non-predominant genotypes, and 140 (11%) were unique. Obvious epidemiological links were found in only 106/231 (46%) patients carrying isolates with non-predominant genotypes suggesting that molecular surveillance identified twice as many clusters as those that may have been suspected with classical epidemiological links. However, not all of these molecular clusters represented person-to-person transmission. Thus, molecular typing cannot replace classical epidemiology but is complementary. A prospective surveillance of MRSA genotypes could help to target epidemiological tracking in order to recognise new risk factors in hospital and community settings, or emergence of new epidemic clones.

[Tick-borne encephalitis in the North part of the canton de Vaud]. / Méningo-encéphalite verno-estivate dans le Nord vaudois.

Tick-borne encephalitis (TBE) is described in Switzerland since 1969. More than 200 cases are reported every year to the Federal office of public health (FOPH) and new sites of endemic disease have been documented recently, in particular in the North part of the canton de Vaud. The aim of this article is to review the clinical pictures of 11 patients hospitalised in Yverdon-les-Bains with a diagnosis of TBE between 2003 and August 2007. The occurrence of 5 new cases exposed in the North part of the canton de Vaud over these last 18 months confirms the presence of endemic foci in this area and should prompt the vaccination against the MEVE which is recommended by the FOPH in endemic zones. The sequels of MEVE being observed mainly in the elderly, vaccination should be afforded also to this group of patients.

[Infection of a total knee prosthesis with Brucella spp]. / Infection d'une prothèse totale du genou par "Brucella spp".

Brucellosis, an "anthropophitic" disease of worldwide distribution can involve several organs and tissues but the osteoarticular disease is the most common complication. It can occur as sacroiliitis, bursitis, tenosynovitis or osteomyelitis. Prosthetic joint infection is a serious complication of total joint arthroplasty, with coagulase negative staphylococci and Staphylococcus aureus accounting for 50% of cases. Treatment of prosthetic infections remains complex. Prosthetic infections caused by Brucella spp are rarely described in the literature. We report a patient with a prosthetic joint infection due to Brucella spp, documented by a polymerase chain reaction. The patient has been cured after two-stage exchange of the prosthesis and long-term antimicrobial therapy.

[Evidence of new foci of tick-borne encephalitis in the French speaking part of Switzerland]. / Evidence de nouveaux foyers d'endémie de méningo-encéphalite verno-estivale en Suisse romande.

The incidence of tick-borne encephalitis (TBE) has more than doubled in Switzerland in recent years. In the French part of Switzerland several patients seem to have acquired the infection outside of known endemic foci. Thirty patients with TBE living or having acquired the infection in the French speaking part of Switzerland between 2000 and 2005 were identified. For one patient it wasn't possible to obtain precise information about the place of acquisition of the infection and 16 patients were infected in known endemic foci. Among the 13 remaining patients, 6 were infected on the southern shores of the lake of Neuchâtel and 7 in the plaine of Orbe. We conclude that there are new foci of TBE in the northern regions of the canton of Vaud. Vaccination should be proposed to the population at risk of these regions. In addition it is important that persons with outdoor activities in this regions respect the preventive

Piperacillin-tazobactam monotherapy in high-risk febrile and neutropenic cancer patients.

Combination therapy with a beta-lactam plus an aminoglycoside has been the standard approach for treating febrile neutropenia for many years. More recently, beta-lactam monotherapy has also been shown to be a reliable and safe approach. In the present study, 763 eligible patients with fever and neutropenia received piperacillin-tazobactam monotherapy. On day 3, according to the study protocol, 165 patients with persistent fever who fulfilled the study entry criteria were randomised to receive vancomycin or a placebo. The success rate was 51% in the intention-to-treat analysis and 62% in the per-protocol analysis. The overall mortality rate was 8% (58/763), with only 18 (2.4%) deaths attributed to the initial or subsequent infection. Randomisation had no influence on the study endpoints. The adverse event rate was evaluated only in the patient population not included in the randomised part of the study. Among these patients, adverse events probably or definitely related to piperacillin-tazobactam therapy were uncommon, confirming the favourable safety profile of piperacillin-tazobactam. It was concluded that piperacillin-tazobactam could be considered as monotherapy for patients with high-risk febrile neutropenia.

Cost-effectiveness of full-course oral levofloxacin in severe community-acquired pneumonia.

Oral levofloxacin is as efficient as sequential antibiotic treatment in community-acquired pneumonia (CAP). The current authors assessed whether oral levofloxacin treatment of patients with severe CAP, followed-up for 30 days, would save money. Over a 12-month period, 129 hospitalised patients with severe non-intensive care unit CAP were randomly assigned to receive either oral levofloxacin or sequential antibiotic treatment. Direct and indirect costs were compared over a 30-day period from several perspectives. CAP resolved in 71 out of 77 oral levofloxacin (92%) and in 34 out of 37 sequential antibiotic treatment patients (92%). Patients' characteristics, treatment duration, hospital length of stay and mortality were similar in both groups. Drug acquisition costs were 1.7-times smaller in oral levofloxacin patients, who were less often transferred to rehabilitation centres, but they used more physicians' visits during follow-up and their total costs were lower. As only a minority of patients was still active, inability to work and, hence, indirect costs were similar in both groups. In this study, oral levofloxacin for severe non-intensive care unit community-acquired pneumonia was equally effective as sequential antibiotic treatment, but did not lead to major costs savings except for drug acquisition costs. External factors linked with patients' characteristics and/or medical practice are likely to play a role and should be addressed.

[Treatment with oral antibiotics of febrile neutropenia in onco-haematology. The experience of the EORTC antimicrobial group]. / Traitement antibiotique oral des neutropénies fébriles en onco-hématologie. L'expérience du groupe antimicrobien de l'EORTC.

THE CONTEXT: Up until the nineties, the intravenous administration of a broad spectrum antibiotic was the classical treatment of any patient presenting with febrile neutropenia. Since then, in patients considered at low risk and with expected of neutropenia less than 7-10 days, oral antibiotherapy has become an attractive option. TWO LARGE STUDIES: A study by the antimicrobial group of the EORTC (European organisation for research and treatment of cancer) and a North American study have compared the efficacy of an oral combination of ciprofloxacine and amoxicillin/clavulanic acid with that of an intravenous antibiotherapy in low-risk patients presenting febrile neutropenia. In both studies, the success rate was the same in the group of patients treated with oral antibiotics and those treated with intravenous antibiotics. RESERVATIONS: These two studies were conducted in hospitalised patients. No conclusions can be drawn with regard to out-patient treatment. Out-patient management would only be possible after appropriate selection of patients at low risk.

Full-course oral levofloxacin for treatment of hospitalized patients with community-acquired pneumonia.

Most guidelines for the management of hospitalized patients with community-acquired pneumonia (CAP) recommend commencing therapy with intravenous antibiotics, primarily because of concern about absorption of oral antibiotics in acutely ill patients. However, patients who respond are rapidly switched to oral therapy, which has been shown to reduce costs and to shorten the length of stay. The aim of the present study was to determine whether a full course of oral antibiotics is as efficacious and as safe as intravenous-to-oral sequential antibiotic therapy for the treatment of hospitalized, non-ICU patients with CAP. In an open-labelled, controlled study, 129 hospitalized patients with CAP were randomly assigned in a 2:1 ratio to receive either a full course of oral levofloxacin (500 mg q12 h) or an intravenous-to-oral sequential therapy consisting of intravenous ceftriaxone (2 g q24 h) with or without clarithromycin (500 mg q12 h) followed by an oral antibiotic (a beta-lactam agent in the majority of patients). The primary study endpoint was the resolution of CAP; secondary endpoints included length of stay and overall mortality. CAP resolved in 72 of 79 (91.1%) patients in the levofloxacin group and in 34 of 37 (91.9%) patients in the intravenous-to-oral sequential therapy group (difference, -0.8%, 95%CI, -11.6-10.0). Median length of stay was 8 days (range, 2-74 days) in the levofloxacin group and 10 days (range, 3-29 days) in the intravenous-to-oral sequential therapy group ( P=0.28). Day 30 mortality rates were 1.3% (1 of 79) and 8.1% (3 of 37), respectively (difference, -6.8%, 95%CI, -16.0-2.3). Full-course oral levofloxacin is as efficacious and as safe as standard intravenous-to-oral sequential antibiotic therapy for the treatment of hospitalized patients with CAP.

Cefepime versus imipenem-cilastatin for treatment of nosocomial pneumonia in intensive care unit patients: a multicenter, evaluator-blind, prospective, randomized study.

In a randomized, evaluator-blind, multicenter trial, we compared cefepime (2 g three times a day) with imipenem-cilastatin (500 mg four times a day) for the treatment of nosocomial pneumonia in 281 intensive care unit patients from 13 centers in six European countries. Of 209 patients eligible for per-protocol analysis of efficacy, favorable clinical responses were achieved in 76 of 108 (70%) patients treated with cefepime and 75 of 101 (74%) patients treated with imipenem-cilastatin. The 95% confidence interval (CI) for the difference between these response rates (-16 to 8%) failed to exclude the predefined lower limit for noninferiority of -15%. In addition, therapy of pneumonia caused by an organism producing an extended-spectrum beta-lactamase (ESBL) failed in 4 of 13 patients in the cefepime group but in none of 10 patients in the imipenem group. However, the clinical efficacies of both treatments appeared to be similar in a secondary intent-to-treat analysis (95% CI for difference, -9 to 14%) and a multivariate analysis (95% CI for odds ratio, 0.47 to 1.75). Furthermore, the all-cause 30-day mortality rates were 28 of 108 (26%) patients in the cefepime group and 19 of 101 (19%) patients in the imipenem group (P = 0.25). Rates of documented or presumed microbiological eradication of the causative organism were similar with cefepime (61%) and imipenem-cilastatin (54%) (95% CI, -23 to 8%). Primary or secondary resistance of Pseudomonas aeruginosa was detected in 19% of the patients treated with cefepime and 44% of the patients treated with imipenem-cilastatin (P = 0.05). Adverse events were reported in 71 of 138 (51%) and 62 of 141 (44%) patients eligible for safety analysis in the cefepime and imipenem groups, respectively (P = 0.23). Although the primary end point for this study does not exclude the possibility that cefepime was inferior to imipenem, some secondary analyses showed that the two regimens had comparable clinical and microbiological efficacies. Cefepime appeared to be less active against organisms producing an ESBL, but primary and secondary resistance to imipenem was more common for P. aeruginosa. Selection of a single agent for therapy of nosocomial pneumonia should be guided by local resistance patterns.

Vancomycin versus placebo for treating persistent fever in patients with neutropenic cancer receiving piperacillin-tazobactam monotherapy.

This prospective, double-blind trial assessed whether the addition of a glycopeptide would be able to reduce the time to defervescence in neutropenic patients with cancer who had persistent fever 48-60 h after the initiation of empirical piperacillin-tazobactam monotherapy. Of 763 eligible patients, 165 with persistent fever were randomized to receive piperacillin-tazobactam therapy plus either vancomycin therapy or placebo. Defervescence was observed in 82 (95%) of 86 patients in the vancomycin group and in 73 (92%) of 79 patients in the placebo group (P=.52). The distributions of the time to defervescence were not statistically significant between the 2 groups (estimated hazard ratio, 1.03; 95% confidence interval, 0.75-1.43; P=.75). The number of additional episodes of gram-positive bacteremia and the percentage of patients for whom amphotericin B was empirically added to their therapy regimen were also similar in both groups. This study failed to demonstrate that the empirical addition of vancomycin therapy to the treatment regimen is of benefit to persistently febrile neutropenic patients with cancer.

Thermal behavior of long wavelength absorption transitions in Spirulina platensis photosystem I trimers.

In photosystem I trimers of Spirulina platensis a major long wavelength transition is irreversibly bleached by illumination with high-intensity white light. The photobleaching hole, identified by both absorption and circular dichroism spectroscopies, is interpreted as the inhomogeneously broadened Q(y) transition of a chlorophyll form that absorbs maximally near 709 nm at room temperature. Analysis of the mean square deviation of the photobleaching hole between 80 and 300 K, in the linear electron-phonon frame, indicates that the optical reorganization energy is 52 cm(-1), four times greater than that for the bulk, short-wavelength-absorbing chlorophylls, and the inhomogenous site distribution bandwidth is close to 150 cm(-1). The room temperature bandwidth, close to 18.5 nm, is dominated by thermal (homogeneous) broadening. Photobleaching induces correlated circular dichroism changes, of opposite sign, at 709 and 670 nm, which suggests that the long wavelength transition may be a low energy excitonic band, in agreement with its high reorganization energy. Clear identification of the 709-nm spectral form was used in developing a Gaussian description of the long wavelength absorption tail by analyzing the changing band shape during photobleaching using a global decomposition procedure. Additional absorption states near 720, 733, and 743 nm were thus identified. The lowest energy state at 743 nm is present in substoichiometric levels at room temperature and its presence was confirmed by fluorescence spectroscopy. This state displays an unusual increase in intensity upon lowering the temperature, which is successfully described by assuming the presence of low-lying, thermally populated states.

[Review of infected total arthroplasties of the hip and knee--apropos of 28 cases]. / Revue des arthroplasties totales de la hanche et du genou infectées--à propos de 28 cas.

This study is a long-term analysis of a group of patients with infected arthroplasties of the hip or the knee. We identified 28 patients with an infected arthroplasty (22 hips, 6 knees) documented by bacterial culture or on direct examination. At the time of diagnosis and on follow-up (a mean of 46 months after treatment) we evaluated the clinical picture, the radiological appearances of the articulation and the biological parameters. 19/28 patients showed a typical clinical picture, whereas in 9 others the picture was more doubtful. The treatments were 14 two-stage replacements of the arthroplasties, 7 simple resections, 5 conservative treatments and 2 one-stage replacements. On follow-up, 25 patients were considered as cured of their infection and 3 as failures. From a functional viewpoint, 9 patients showed no limitation, whereas 19 were limited in the daily activity. Half of the patients had no pain. Radiology showed that 20/26 evaluated patients had no signs of recurrence. Paraclinical examinations are important in the diagnosis of persistent low grade infections, particularly the demonstration of bacteria by pre-surgical sampling (fine needle aspiration, culture from draining sinuses). In spite of the cure of infection, the functional and painful sequellae are often considerable. As a result of our experience, we recommend a two-stage surgical procedure. Only when the general condition of the patient is poor, or when the infection is not under control, would we envisage an alternative procedure (arthrodesis, girdelstone, conservative).

[Evaluation of antibiotic prophylaxis in neutropenic patients with hematologic malignancies]. / Evaluation de la prophylaxie antibiotique chez les patients neutropéniques avec hémopathie maligne.

The benefits of oral prophylaxis for neutropenia have remained controversial up to now. We evaluated retrospectively the effect of antibiotic prophylaxis with ciprofloxacin and penicillin on the prevention of bacterial infections in 112 cases of prolonged neutropenia in adult patients treated for haematological malignancies. 41 patients received prophylaxis between December 1993 and November 1994 while 71 patients did not receive prophylaxis between December 1994 and November 1995. There were no significant differences between groups in age, sex, type or stage of haemopathy, type of chemotherapy and duration of neutropenia. The antibiotic prophylaxis reduced the number of overall infections (p = 0.05) and the number of gram-negative bacteraemias (p = 0.02). The median time to the onset of fever, the duration of fever, the duration of antibiotic treatment, the duration of hospitalization or admission to the intensive care unit, the number of serious complications or death were not influenced by antibiotic prophylaxis. The prophylaxis did not reduce the overall incidence of bacteraemia, of clinically documented infections or of fever of unknown origin. This retrospective study confirms that oral prophylaxis with ciprofloxacin and penicillin decreases the incidence of infections and, in particular, of gram-negative bacteraemia, but does not modify the overall morbidity and mortality in our patients. In view of the risk of emergence of bacterial resistance, these data do not support the routine use of oral antibiotic prophylaxis in neutropenic patients with haematological malignancies.

Oral versus intravenous empirical antimicrobial therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.

BACKGROUND: Intravenously administered antimicrobial agents have been the standard choice for the empirical management of fever in patients with cancer and granulocytopenia. If orally administered empirical therapy is as effective as intravenous therapy, it would offer advantages such as improved quality of life and lower cost. METHODS: In a prospective, open-label, multicenter trial, we randomly assigned febrile patients with cancer who had granulocytopenia that was expected to resolve within 10 days to receive empirical therapy with either oral ciprofloxacin (750 mg twice daily) plus amoxicillin-clavulanate (625 mg three times daily) or standard daily doses of intravenous ceftriaxone plus amikacin. All patients were hospitalized until their fever resolved. The primary objective of the study was to determine whether there was equivalence between the regimens, defined as an absolute difference in the rates of success of 10 percent or less. RESULTS: Equivalence was demonstrated at the second interim analysis, and the trial was terminated after the enrollment of 353 patients. In the analysis of the 312 patients who were treated according to the protocol and who could be evaluated, treatment was successful in 86 percent of the patients in the oral-therapy group (95 percent confidence interval, 80 to 91 percent) and 84 percent of those in the intravenous-therapy group (95 percent confidence interval, 78 to 90 percent; P=0.02). The results were similar in the intention-to-treat analysis (80 percent and 77 percent, respectively; P=0.03), as were the duration of fever, the time to a change in the regimen, the reasons for such a change, the duration of therapy, and survival. The types of adverse events differed slightly between the groups but were similar in frequency. CONCLUSIONS: In low-risk patients with cancer who have fever and granulocytopenia, oral therapy with ciprofloxacin plus amoxicillin-clavulanate is as effective as intravenous therapy.