Rapid species identification of Candida directly from blood culture broths by Sepsityper-MALDI-TOF mass spectrometry: impact on antifungal therapy.

Rapid identification of Candida species facilitates pathogen-directed therapy with either fluconazole or an echinocandin. METHOD: We applied Sepsityper matrix-assisted laser desorption ionisation time of flight mass spectrometry (MALDI-TOF-MS) technology on positive blood culture broths for rapid species identification. RESULTS: Of the 74 patients with candidaemia, 25 had the species identified on the day of the positive blood culture directly from the broth (rapid identification group) while the remaining 49 had the species identified from culture (conventional identification group). Three (13.6%) out of 22 treated patients in the rapid identification group received echinocandin compared to 20/45 (44.4%) in the conventional identification group. The appropriateness of therapy was 90.9% in the rapid identification group and 62.2% in the conventional identification group (p = 0.01). Cost savings were more than £10,000 in the first three days of treatment. CONCLUSION: Sepsityper-MALDI-TOF-MS is a useful tool in supporting antifungal stewardship programmes.

Diabetes, malignancy and age as predictors of Candida glabrata bloodstream infection: A re-evaluation of the risk factors.

OBJECTIVE: Echinocandins and azoles are widely used in the treatment of candidaemia. Guidelines of the Infectious Diseases Society of America recommend commencing treatment with an echinocandin in candidaemic patients with risk factors for Candida glabrata i.e. patients who are elderly, or who have diabetes or malignancy, or those with recent prescription of azoles. We attempted to validate whether age, diabetes and malignancy are associated with C. glabrata candidaemia. PATIENTS, MATERIALS AND METHODS: Information in relation to demographics, patient associated risk factors, and laboratory parameters were collected from the casenotes and the laboratory information system. We then analysed the distribution of the risk factors (age, diabetes, and malignancy) in candidaemic patients with C. glabrata and patients with species other than C. glabrata (excluding Candida krusei). RESULTS: Over a 42-month period (April 2011-September 2017), 124 patients had candidaemia. We analysed data for 119 patients of whom 33 (27.7%) had C. glabrata and the remaining 86 (72.2%) were infected with other species. Sixty-five patients were elderly (age≥65), 40 had some form of malignancy, 34 had diabetes, and 4 patients were prescribed azoles in the 30 days prior to candidaemia (many patients had multiple risk factors). Comparing patients with C. glabrata to patients infected with other species, we found no association with diabetes (39.3% vs. 24.4%, P=0.1), malignancy (36.3 vs. 32.5%, P=0.69), and age (54.5% vs. 54.6%, P=0.99). CONCLUSIONS: Diabetes, malignancy and age are not reliable predictors of candidaemia due to C. glabrata.

Future trends in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection: An in-depth review of newer antibiotics active against an enduring pathogen.

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a major public health problem. Vancomycin and teicoplanin have been in clinical use for several decades but their drawbacks are well described. In the last 10 years, several antibiotics have been made available for clinical use. Daptomycin and linezolid have been extensively used during this period. Other agents such as ceftaroline, ceftobiprole, dalbavancin, oritavancin, tedizolid and telavancin have been approved by regulatory agencies since 2009. Many others, such as the newer tetracyclines, fluoroquinolones, oxazolidinones and pleuromutilins, are in various stages of development. In addition, an ongoing multicentre trial is investigating the role of combination of vancomycin or daptomycin with ß-lactam antibiotics. This review discusses the role of the newer antibiotics, reflecting the views of the 6th MRSA Consensus Conference meeting of the International Society of Chemotherapy MRSA Working Group that took place in 2016.

Investigation of outbreaks of Pneumocystis jirovecii pneumonia in two Scottish renal units.

Pneumocystis jirovecii is recognized as an opportunistic pathogen. In recent years, human-to-human transmission of P. jirovecii has been demonstrated. However, outbreaks of P. jirovecii infections are not well defined because the epidemiological setting that facilitates transmission is not fully understood. This article describes two outbreaks of P. jirovecii pneumonia (PCP) in renal transplant patients in the West of Scotland. In total, 25 patients in two geographically contiguous locations were affected. Allele B was identified as the dominant type, along with allele A3. It was not possible to determine the exact reason for clustering of cases, although the outpatient clinic setting featured in one of the outbreaks. The outbreaks ceased with the use of trimethoprim-sulphamethoxazole prophylaxis; the target populations that received prophylaxis were different in the two outbreaks. Infection control teams should be alert to the possibility of outbreaks of PCP.

Genomic insights into the emergence and spread of international clones of healthcare-, community- and livestock-associated meticillin-resistant Staphylococcus aureus: Blurring of the traditional definitions.

The evolution of meticillin-resistant Staphylococcus aureus (MRSA) from meticillin-susceptible S. aureus has been a result of the accumulation of genetic elements under selection pressure from antibiotics. The traditional classification of MRSA into healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) is no longer relevant as there is significant overlap of identical clones between these groups, with an increasing recognition of human infection caused by livestock-associated MRSA (LA-MRSA). Genomic studies have enabled us to model the epidemiology of MRSA along these lines. In this review, we discuss the clinical relevance of genomic studies, particularly whole-genome sequencing, in the investigation of outbreaks. We also discuss the blurring of each of the three epidemiological groups (HA-MRSA, CA-MRSA and LA-MRSA), demonstrating the limited relevance of this classification.

Pasteurella multocida infected total knee arthroplasty: a case report and review of the literature.

Pasteurella multocida is a rare cause of prosthetic joint infection. This infection generally follows significant animal contact, usually licks and scratches. We report a case of P multocida infection that was treated with linezolid with salvage of the implant. Linezolid is generally active against Gram-positive organisms only with the exception of Pasteurella, which is Gram-negative. We extensively review the previous reported cases of implant infection with P multocida.

Antifungal step-down therapy based on hospital intravenous to oral switch policy and susceptibility testing in adult patients with candidaemia: a single centre experience.

AIMS: Echinocandins are recommended for the treatment of candidaemia in moderately severe to severely ill patients. Step-down or de-escalation from echinocandin to fluconazole is advised in patients who are clinically stable but data in relation to step-down therapy are sparse. Using our hospital intravenous to oral switch therapy (IVOST) policy to guide antifungal de-escalation in patients with candidaemia, we aimed to determine what proportion of patients are de-escalated to fluconazole, the timescale to step-down, associated reduction in consumption of echinocandins and antifungal cost savings. METHODOLOGY: Patients with candidaemia were followed from April 2011 to March 2013. RESULTS: A total of 37 episodes of candidaemia were documented during the study period. Twenty-seven patients were commenced on an echinocandin or voriconazole and 19 (70.3%) were de-escalated to fluconazole based on the IVOST policy. The mean and median number of days to de-escalation of therapy was 4.6 and 5 days, respectively. One patient whose therapy was de-escalated relapsed. The overall 30 day crude mortality was 37.1%. The step-down approach led to significant saving in antifungal drug cost of £1133.88 per candidaemic episode and £2208.08 per de-escalation. CONCLUSION: Implementation of IVOST policy led to streamlining of antifungal therapy.

Candidaemia in the non-neutropenic patient: a critique of the guidelines.

Several guidelines have been published on the management of candidaemia. These guidelines vary in their recommendations, and the lack of consistency between the guidelines has implications for the management of candidaemia. We critiqued five guidelines, including the Infectious Diseases Society of America (IDSA) Guidelines for the Management of Candidiasis, the Canadian Clinical Practice Guidelines for Invasive Candidiasis in Adults, the Joint Recommendations of the German Speaking Mycological Society and the Paul-Ehrlich-Society for Chemotherapy, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Guideline for the Diagnosis and Management of Candida Diseases, and the Brazilian Guidelines for the Management of Candidiasis. The recommendations in these guidelines vary in all major areas of management, including choice of initial therapy, species-specific therapy (Candida glabrata and Candida parapsilosis), transition to oral therapy (3 days as per IDSA but 10 days as per ESCMID), catheter removal and specialty referrals. We found that too much emphasis has been placed on themes such as predicting the infecting species (and therefore fluconazole susceptibility) or the need for investigations such as echocardiography. We also stress that guidelines fail to provide adequate information (due to lack of evidence) on the most relevant issues that clinicians face when managing candidaemia, such as the place for fluconazole in the treatment of C. glabrata, the clinical relevance of dose-dependent susceptibility to fluconazole, and the timing of step-down therapy.

Vancomycin in the treatment of meticillin-resistant Staphylococcus aureus (MRSA) infection: End of an era?

Infection with meticillin-resistant Staphylococcus aureus (MRSA) continues to have significant morbidity and mortality. Vancomycin, which has been the mainstay of treatment of invasive MRSA infections, has several drawbacks related to its pharmacological properties as well as varying degrees of emerging resistance. These resistant subpopulations are difficult to detect, making therapy with vancomycin less reliable. The newer agents such as linezolid, daptomycin, ceftaroline, and the newer glycopeptides telavancin and oritavancin are useful alternatives that could potentially replace vancomycin in the treatment of certain conditions. By summarising the discussions that took place at the III MRSA Consensus Conference in relation to the current place of vancomycin in therapy and the potential of the newer agents to replace vancomycin, this review focuses on the challenges faced by the laboratory and by clinicians in the diagnosis and treatment of MRSA infections.

Epidemiology and management of candidaemia--a retrospective, multicentre study in five hospitals in the UK.

Candidaemia is associated with high mortality. Despite the fact that Candida species account for close to 10% of all nosocomial bloodstream infections, relatively few studies have investigated the management of candidaemia in hospitals. Our objective was to find out how candidaemia is managed in hospitals. Data relating to all episodes of candidaemia for the year 2008 were retrospectively collected in five centres in Scotland and Wales. A total of 96 candidaemic episodes were recorded in the year 2008, yielding 103 isolates of Candida. Fifty candidaemic episodes were caused by Candida albicans. Fluconazole was the most common agent prescribed for the treatment of candidaemia. There was great variation in the prescribed dose of fluconazole. Forty per cent of patients who survived received <2 weeks of systemic antifungal therapy. Central venous catheters (CVC) were removed in 57% of patients. CVC removal was not associated with better survival. The overall mortality was 40.4%. Management of candidaemia varies between the UK centres and is often inadequate. There is need to have consensus on the dosages of antifungal agents and the duration of therapy. The current guidance on removal of CVC in all cases of candidaemia should be reviewed.

Management of fungal infections in the intensive care unit: a survey of UK practice.

BACKGROUND: Candida species are a common cause of nosocomial bloodstream infection. Such infections commonly affect patients in the intensive care unit (ICU) and carry a high mortality. There are published guidelines for the management of fungal infections, but there are no data on the usual management of invasive Candida infections in UK ICUs. METHODS: An electronic survey was sent by email to a representative clinician in 236 ICUs, over 90% of units in the UK. Questions related to the institution of empirical therapy and to the management of proven candidaemia. RESULTS: There were 72 responses. A minority of units follow a policy regarding the management of these infections but the involvement of microbiologists is usual. Empirical therapy is used in 85.9% of units, often for patients perceived to be at high risk. Fluconazole is the most commonly used antifungal agent, both for empirical therapy and for the treatment of proven candidaemia. For candidaemic patients, 73.9% of ICUs frequently or always remove central venous catheters within 48 h, while 15.1% frequently or always arrange ophthalmology review. CONCLUSIONS: Management of fungal infections is relatively consistent among responding units. However, recent developments in the field have not yet been incorporated into standard practice. Adherence to published guidelines could be improved, potentially reducing morbidity and mortality from these common infections.

Antibiotic heterogeneity: from concept to practice.

Bacterial resistance to multiple antibiotics is a serious and emerging threat. Several measures have been proposed to curb this growing trend. These include prescribing restrictions, education, and infection control that target transmission, among several others. Antibiotic cycling has been a subject of debate, and although many investigators have studied the utility of antibiotic cycling with the help of theoretical models or as part of clinical investigations, several areas remain undefined and unclear. This review summarizes the available information on antibiotic heterogeneity (antibiotic cycling, antibiotic mixing, and other types of antibiotic protocols) with a critical analysis of the published studies.

The echinocandins: three useful choices or three too many?

Echinocandins act by inhibiting 1,3-beta-D-glucan synthesis in the fungal cell wall. The three licensed agents in this class, namely anidulafungin, caspofungin and micafungin, have a favourable pharmacological profile. These agents are narrow spectrum with clinically relevant activity against Candida and Aspergillus spp. Several trials have established the non-inferiority of these agents over existing agents in the treatment of invasive fungal infections. Caspofungin is also licensed for empirical antifungal therapy of presumed fungal infections in patients with febrile neutropenia. This paper reviews the literature on echinocandins.

Unusual clinical manifestations of leptospirosis.

Leptospirosis has protean clinical manifestations. The classical presentation of the disease is an acute biphasic febrile illness with or without jaundice. Unusual clinical manifestations may result from involvement of pulmonary, cardiovascular, neural, gastrointestinal, ocular and other systems. Immunological phenomena secondary to antigenic mimicry may also be an important component of many clinical features and may be responsible for reactive arthritis. Leptospirosis in early pregnancy may lead to fetal loss. There are a few reports of leptospirosis in HIV-infected individuals but no generalisation can be made due to paucity of data. It is important to bear in mind that leptospiral illness may be a significant component in cases of dual infections or in simultaneous infections with more than two pathogens.