The Dutch Working Party on Antibiotic Policy (SWAB) Recommendations for the Diagnosis and Management of Febrile Neutropenia in Patients with Cancer.

INTRODUCTION: This guideline was written by a multidisciplinary committee with mandated members of the Dutch Society for Infectious Diseases, Dutch Society for Hematology, Dutch Society for Medical Oncology, Dutch Association of Hospital Pharmacists, Dutch Society for Medical Microbiology, and Dutch Society for Pediatrics. The guideline is written for adults and pediatric patients. METHOD: The recommendations are based on the answers to nine questions formulated by the guideline committee. To provide evidence-based recommendations we used all relevant clinical guidelines published since 2010 as a source, supplemented with systematic searches and evaluation of the recent literature (2010-2020) and, where necessary, supplemented by expert-based advice. RESULTS: For adults the guideline distinguishes between high- and standard-risk neutropenia based on expected duration of neutropenia (> 7 days versus ≤ 7 days). Where possible a distinction has been made between pediatric and adult patients. CONCLUSION: This guideline was written to aid diagnosis and management of patients with febrile neutropenia due to chemotherapy in the Netherlands. The guideline provides recommendation for children and adults. Adults patient are subdivided as having a standard- or high-risk neutropenic episode based on estimated duration of neutropenia. The most important recommendations are as follows. In adults with high-risk neutropenia (duration of neutropenia > 7 days) and in children with neutropenia, ceftazidime, cefepime, and piperacillin-tazobactam are all first-choice options for empirical antibiotic therapy in case of fever. In adults with standard-risk neutropenia (duration of neutropenia ≤ 7 days) the MASCC score can be used to assess the individual risk of infectious complications. For patients with a low risk of infectious complications (high MASCC score) oral antibiotic therapy in an outpatient setting is recommended. For patients with a high risk of infectious complications (low MASCC score) antibiotic therapy per protocol sepsis of unknown origin is recommended.

Renal transplant patient survives a donor-derived abdominal invasive mucormycosis (Lichtheimia ramos a).

Mucormycosis is a life-threatening invasive fungal infection, most commonly described in severely immunocompromised patients. It is characterized by rapid invasive growth of the fungus and often with fatal outcome. We report a case of a renal transplant recipient diagnosed with a donor-derived invasive mucormycosis. In this patient, we used a step-wise approach of withdrawal of immunosuppressants, antifungal induction therapy, extensive surgical debridement of all (potentially) infected tissue, abdominal irrigation of liposomal amphotericin B and interferon gamma. Due to rapid diagnosis and intensive therapy the patient survived.

[Revised multidisciplinary guidelines 'Varicella'; broader indication for post-exposure prophylaxis]. / Herziene multidisciplinaire richtlijn 'Varicella'.

Post-exposure prophylaxis (PEP) with varicella zoster immunoglobulins (VZIG) should be administered as soon as possible after exposure to the virus, but always within ten days; in the previous guidelines this was within 96 hours. In cases of perinatal exposure, PEP with VZIG should be administered to neonates if the mother develops clinical chickenpox between seven days before delivery and seven days after delivery; in the previous guidelines this was between five days before delivery and two days after delivery. A new chapter on the treatment of chickenpox has been added to the guidelines.

Early discontinuation of empirical antibiotic treatment in neutropenic patients with acute myeloid leukaemia and high-risk myelodysplastic syndrome.

INTRODUCTION: Current guidelines advocate empirical antibiotic treatment (EAT) in haematological patients with febrile neutropenia. However, the optimal duration of EAT is unknown. In 2011, we have introduced a protocol, promoting discontinuation of carbapenems as EAT after 3 days in most patients and discouraging the standard use of vancomycin. This study assesses the effect of introducing this protocol on carbapenem and vancomycin use in high-risk haematological patients and its safety. METHODS: A retrospective before-after study was performed comparing a cohort from 2007 to 2011 (period I, before restrictive EAT use) with a cohort from 2011 to 2014 (period II, restrictive EAT use). Neutropenic episodes related to chemotherapy or stem cell transplantation (SCT) in patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) were analysed. The primary outcome was the use of carbapenems and vancomycin as EAT during neutropenia, expressed as days of therapy (DOT)/100 neutropenic days and analysed with interrupted time series (ITS). Also the use of other antibiotics was analysed. Safety measurements included 30-day mortality, ICU admittance within 30 days after start of EAT and positive blood cultures with carbapenem-susceptible microorganisms. RESULTS: Three hundred sixty-two neutropenic episodes with a median duration of 18 days were analysed, involving 201 patients. ITS analysis showed decreased carbapenem use with a step change of - 16.1 DOT/100 neutropenic days (95% CI - 26.77 to - 1.39) and an overall reduction of 21.6% (8.7 DOT/100 neutropenic days). Vancomycin use decreased with a step change of - 13.7 DOT/100 neutropenic days (95% CI - 23.75 to - 3.0) and an overall reduction of 54.7% (14.6 DOT/100 neutropenic days). The use of all antibiotics combined decreased from 155.6 to 138 DOT/100 neutropenic days, a reduction of 11.3%. No deaths directly related to early discontinuation of EAT were identified, also no notable difference in ICU-admission (9/116 in period I, 9/152 in period II) and positive blood cultures (4/116 in period I, 2/152 in period II) was detected. CONCLUSION: The introduction of a protocol promoting restrictive use of EAT resulted in reduction of carbapenem and vancomycin use and appears to be safe in AML or high-risk MDS patients with febrile neutropenia during chemotherapy or SCT.

A tailored implementation strategy to reduce the duration of intravenous antibiotic treatment in community-acquired pneumonia: a controlled before-and-after study.

We previously showed that 40 % of clinically stable patients hospitalised for community-acquired pneumonia (CAP) are not switched to oral therapy in a timely fashion because of physicians' barriers. We aimed to decrease this proportion by implementing a novel protocol. In a multi-centre controlled before-and-after study, we evaluated the effect of an implementation strategy tailored to previously identified barriers to an early switch. In three Dutch hospitals, a protocol dictating a timely switch strategy was implemented using educational sessions, pocket reminders and active involvement of nursing staff. Primary outcomes were the proportion of patients switched timely and the duration of intravenous antibiotic therapy. Length of hospital stay (LOS), patient outcome, education effects 6 months after implementation and implementation costs were secondary outcomes. Statistical analysis was performed using mixed-effects models. Prior to implementation, 146 patients were included and, after implementation, 213 patients were included. The case mix was comparable. The implementation did not change the proportion of patients switched on time (66 %). The median duration of intravenous antibiotic administration decreased from 4 days [interquartile range (IQR) 2-5] to 3 days (IQR 2-4), a decrease of 21 % [95 % confidence interval (CI) 11 %; 30 %) in the multi-variable analysis. LOS and patient outcome were comparable before and after implementation. Forty-three percent (56/129) of physicians attended the educational sessions. After 6 months, 24 % (10/42) of the interviewed attendees remembered the protocol's main message. Cumulative implementation costs were 5,798 (20/reduced intravenous treatment day). An implementation strategy tailored to previously identified barriers reduced the duration of intravenous antibiotic administration in hospitalised CAP patients by 1 day, at minimal cost.

Cause-specific long-term mortality rates in patients recovered from community-acquired pneumonia as compared with the general Dutch population.

Insights into long-term mortality, especially into the cause of death after initial recovery from an episode of community-acquired pneumonia (CAP), may help in determining optimal preventive measures in such patients. Prospective observational cohort studies were conducted to compare cause-specific long-term mortality rates for 356 patients who had recovered from CAP with those of the general Dutch population (16.3 million) between 2003 and 2007. The Dutch Municipal Public Records Database and death certificates were used to determine cause-specific mortality rates up to 7 years after discharge. In patients who had recovered from CAP, cumulative 1-year, 5-year and 7-year mortality rates were 17%, 43% and 53%, respectively, as compared with 4%, 19% and 24% for an age-matched and sex-matched population reference cohort. Overall, patients who had recovered from CAP had significantly higher long-term mortality than matched population controls (rate ratio (RR) 3.6; p <0.001). In the years after an episode of CAP, malignancy (27%), chronic obstructive pulmonary disease (COPD) (19%) and cardiovascular disease (16%) were the most frequent causes of death. Only 6% died of pneumonia, as compared with 3.2% in the general population. After initial recovery from an episode of CAP, long-term mortality rates are more than three times as high as in the general population. The causes of long-term mortality were mostly comorbidity-related, and significantly different from those in the general population. After an episode of CAP, optimization of treatment of comorbidities, such as treatment for COPD, might improve long-term survival rates.

Time for first antibiotic dose is not predictive for the early clinical failure of moderate-severe community-acquired pneumonia.

The time to first antibiotic dose (TFAD) has been mentioned as an important performance indicator in community-acquired pneumonia (CAP). However, the advice to minimise TFAD to 4 hours (4 h) is only based on database studies. We prospectively studied the effect of minimising the TFAD on the early clinical outcome of moderate-severe CAP. On admission, patients' medical data and TFAD were recorded. Early clinical failure was expressed as the proportion of patients with clinical instability, admission to the intensive care unit (ICU) or mortality on day three. Of 166 patients included in the study, 27 patients (29.7%) with TFAD <4 h had early clinical failure compared to 23 patients (37.7%) with TFAD >4 h (odds ratio [OR] 0.69; 95% confidence interval [CI] 0.35-1.35). In multivariate analysis, the pneumonia severity index (OR 1.03; 95%CI 1.01-1.04), confusion (OR 2.63; 95%CI 1.14-6.06), Staphylococcus aureus infection (OR 7.26; 95%CI 1.33-39.69) and multilobar pneumonia (OR 2.40; 95%CI 1.11-5.22) but not TFAD were independently associated with early clinical failure. Clinical parameters on admission other than the TFAD predict early clinical outcome in moderate-severe CAP. In contrast to severe CAP necessitating treatment in the ICU directly, in the case of suspected moderate-severe CAP, there is time to establish a reliable diagnosis of CAP before antibiotics are administered. Therefore, the implementation of the TFAD as a performance indicator is not desirable.

Usefulness of consecutive C-reactive protein measurements in follow-up of severe community-acquired pneumonia.

Despite the introduction of new inflammatory markers, C-reactive protein (CRP) remains commonly used in patients hospitalised with severe infections. However, evidence on the usefulness of consecutive CRP measurements is still unclear. The clinical relevance of consecutive CRP measurements was studied in follow-up of antibiotic treatment in patients with severe community-acquired pneumonia (CAP). In a prospective multicentre trial, CRP levels were measured on admission, and on days 3 and 7. Patients were followed clinically for 28 days. Aetiology could be determined in 137 (47.4%) out of the 289 patients included. In 122 (38.8%) patients, initial antibiotic therapy was appropriate. A decline of <60% in CRP levels in 3 days and a decline of <90% in CRP levels in 7 days were both associated with an increased risk of having received inappropriate empiric antibiotic treatment (day 0-3, odds ratio (OR) 6.98, 95% confidence interval (CI) 1.56-31.33 and day 0-7, OR 3.74, 95% CI 1.12-13.77). In conclusion, consecutive C-reactive protein measurements are useful in the first week in follow-up of antibiotic treatment for severe community-acquired pneumonia when taking the causative microorganism and use of steroids into account. A delayed normalisation of C-reactive protein levels is associated with a higher risk of having received inappropriate antibiotic treatment.