Outbreak of KPC-producing Klebsiella pneumoniae at a Portuguese university hospital: Epidemiological characterization and containment measures.

Background: KPC-producing K pneumoniae (KPC-Kp) is a public health problem with important clinical and epidemiological implications. We describe an outbreak of KPC-Kp at vascular surgery and neurosurgery wards in a central hospital in Porto, Portugal. Methods: A case of KPC-Kp was considered to be a patient positive for KPC-Kp with strong epidemiological plausibility of having acquired this microorganism in the affected wards and/or with genetic relationship ≥92% between KPC-Kp isolates. Active surveillance cultures (ASCs) and real-time polymerase chain reaction were used for the detection of carbapenemase genes through rectal swab in a selected population. Molecular analysis was performed using pulsed-field gel electrophoresis at the National Reference Laboratory. Patient risk factors were collected from the electronic medical record system. Information regarding outbreak containment strategy was collected from the Infection Control Unit records. Results: Of the 16 cases, 11 (69%) were identified through active screening, representing 1.4% of the total 766 ASCs collected. The most frequent risk factors identified were previous admission (63%), antibiotic exposure in the past 6 months (50%), and immunodepression (44%). The length of stay until KPC-Kp detection was high (0-121 days, mean 35.6), as was the total length of stay (5-173 days, mean 56.6). Three patients (19%) were infected by KPC-Kp, 2 of whom died. One previously colonized patient died later because of KPC-Kp infection. Conclusions: Multifactorial strategy based on contact precautions (with patient and healthcare professional cohorts) and ASC, as well as Antibiotic Stewardship Program reinforcement, allowed to contain this KPC-Kp outbreak.

Persuasive antimicrobial stewardship intervention in the context of a KPC outbreak: a controlled interrupted time series analysis.

INTRODUCTION: Antimicrobial resistance is a major public health threat. Antimicrobial stewardship (AMS) is one of the key strategies to overcome resistance, but robust evidence on the effect of specific interventions is lacking. We report an interrupted time series (ITS) analysis of a persuasive AMS intervention implemented during a KPC producing Klebsiella pneumoniae outbreak. METHODS: A controlled ITS for carbapenem consumption, total antibiotic consumption and antibiotic-free days, between January 2012 and May 2018 was performed, using segmented regression analysis. The AMS intervention was implemented in the Vascular Surgery ward starting on April 2016 in the context of a KPC outbreak. The General Surgery ward was taken as a control group. Data were aggregated by month for both wards, including 51 pre-intervention and 26 intervention points. RESULTS: The AMS intervention produced a level change in carbapenem consumption of - 11.14 DDDs/100 patient-days accompanied by a decreasing trend of total antibiotic consumption and stable rate of antibiotic-free days in Vascular Surgery ward. These differences were not apparent in the control group. No differences in mortality or readmission rates between pre-intervention and intervention periods were noticed in any of the groups. CONCLUSION: Persuasive AMS interventions on top of previously implemented restrictive interventions can reduce carbapenem consumption without increasing total antibiotic consumption. Starting persuasive AMS interventions in an outbreak setting does not compromise the sustainability of the intervention.

[Protocol for the Prevention of Infections Related to the Treatment of Hematological Malignancies]. / Protocolo de Prevenção de Infeções Relacionadas com o Tratamento de Neoplasias Hematológicas.

Patients with haematological malignancies have a higher incidence of infection compared with the general population. Several factors contribute to this but specially chemotherapy drugs carry different and specific infectious risks. This protocol discusses the prevention of infections in patients who will undergo chemotherapy for the treatment of haematological malignancies. It is divided into: study prior to the initiation of chemotherapy; vaccination and eradication prior to initiation of chemotherapy; antimicrobial prophylaxis during chemotherapy; special situations. The main aims of this protocol are to serve as support to a more systematic and individualized approach to patients undergoing chemotherapy for the treatment of haematological malignancies and by doing so prevent the infectious complications that may arise.

Os doentes com doença hematológica neoplásica apresentam uma incidência de infeções superior à da população geral. Vários fatores contribuem para este aumento de incidência destacando-se os fármacos quimioterápicos que acarretam riscos infeciosos diferentes e específicos. Este protocolo versa a prevenção de infeções em doentes que vão ser submetidos a quimioterapia para tratamento de neoplasias hematológicas. Divide-se em: estudo prévio ao início de quimioterapia; vacinação e erradicações prévias ao início de quimioterapia; profilaxias antimicrobianas durante a quimioterapia; situações especiais. Pretende-se com este protocolo uma abordagem sistematizada e individualizada da situação clínica de cada doente de forma a prevenir de forma a prevenir de infeções emdoentes sob quimioterapia para tratamento de neoplasias hematológicas.

Nocardia infections among immunomodulated inflammatory bowel disease patients: A review.

Human nocardiosis, caused by Nocardia spp., an ubiquitous soil-borne bacteria, is a rare granulomatous disease close related to immune dysfunctions. Clinically can occur as an acute life-threatening disease, with lung, brain and skin being commonly affected. The infection was classically diagnosed in HIV infected persons, organ transplanted recipients and long term corticosteroid treated patients. Currently the widespread use of immunomodulators and immunossupressors in the treatment of inflammatory diseases changed this scenario. Our purpose is to review all published cases of nocardiosis in immunomodulated patients due to inflammatory diseases and describe clinical and laboratory findings. We reviewed the literature concerning human cases of nocardiosis published between 1980 and 2014 in peer reviewed journals. Eleven cases of nocardiosis associated with anti-tumor necrosis factor (TNF) prescription (9 related with infliximab and 2 with adalimumab) were identified; 7 patients had inflammatory bowel disease (IBD), 4 had rheumatological conditions; nocardia infection presented as cutaneous involvement in 3 patients, lung disease in 4 patients, hepatic in one and disseminated disease in 3 patients. From the 10 cases described in IBD patients 7 were associated with anti-TNF and 3 with steroids and azathioprine. In conclusion, nocardiosis requires high levels of clinical suspicion and experience of laboratory staff, in order to establish a timely diagnosis and by doing so avoid worst outcomes. Treatment for long periods tailored by the susceptibility of the isolated species whenever possible is essential. The safety of restarting immunomodulators or anti-TNF after the disease or the value of prophylaxis with cotrimoxazole is still debated.

Nocardia-induced granulocyte macrophage colony-stimulating factor is neutralized by autoantibodies in disseminated/extrapulmonary nocardiosis.

BACKGROUND: Nocardia species cause infections in both immunocompromised and otherwise immunocompetent patients, although the mechanisms defining susceptibility in the latter group are elusive. Anticytokine autoantibodies are an emerging cause of pathogen-specific susceptibility in previously healthy human immunodeficiency virus-uninfected adults, including anti-granulocyte macrophage colony-stimulating factor (GM-CSF) autoantibodies with cryptococcal meningitis. METHODS: Plasma from patients with disseminated/extrapulmonary nocardiosis and healthy controls was screened for anticytokine autoantibodies using a particle-based approach. Autoantibody function was assessed by intranuclear staining for GM-CSF-induced STAT5 phosphorylation in normal cells incubated with either patient or normal plasma. GM-CSF-mediated cellular activation by Nocardia was assessed by staining for intracellular cytokine production and intranuclear STAT5 phosphorylation. RESULTS: We identified neutralizing anti-GM-CSF autoantibodies in 5 of 7 patients studied with central nervous system nocardiosis and in no healthy controls (n = 14). GM-CSF production was induced by Nocardia in vitro, suggesting a causative role for anti-GM-CSF autoantibodies in Nocardia susceptibility and dissemination. CONCLUSIONS: In previously healthy adults with otherwise unexplained disseminated/extrapulmonary Nocardia infections, anti-GM-CSF autoantibodies should be considered. Their presence may suggest that these patients may be at risk for later development of pulmonary alveolar proteinosis or other opportunistic infections, and that patients may benefit from therapeutic GM-CSF administration.