Showing papers in "Expert Review of Anti-infective Therapy in 2013"
TL;DR: This review aims to consolidate clinically relevant background information on the ESKAPE pathogens and provide a contemporary summary of bacterial resistance, alongside pertinent microbiological considerations necessary to face the mounting threat of antimicrobial resistance.
Abstract: In recent years, the Infectious Diseases Society of America has highlighted a faction of antibiotic-resistant bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) - acronymically dubbed 'the ESKAPE pathogens' - capable of 'escaping' the biocidal action of antibiotics and mutually representing new paradigms in pathogenesis, transmission and resistance. This review aims to consolidate clinically relevant background information on the ESKAPE pathogens and provide a contemporary summary of bacterial resistance, alongside pertinent microbiological considerations necessary to face the mounting threat of antimicrobial resistance.
1,039 citations
TL;DR: The evidence that asymptomatic malaria infection plays an important role in malaria transmission is reviewed and that interventions to target this parasite reservoir may be needed to achieve malaria elimination in both low- and high-transmission areas.
Abstract: Scale-up of malaria control interventions has resulted in a substantial decline in global malaria morbidity and mortality. Despite this achievement, there is evidence that current interventions alone will not lead to malaria elimination in most malaria-endemic areas and additional strategies need to be considered. Use of antimalarial drugs to target the reservoir of malaria infection is an option to reduce the transmission of malaria between humans and mosquito vectors. However, a large proportion of human malaria infections are asymptomatic, requiring treatment that is not triggered by care-seeking for clinical illness. This article reviews the evidence that asymptomatic malaria infection plays an important role in malaria transmission and that interventions to target this parasite reservoir may be needed to achieve malaria elimination in both low- and high-transmission areas.
401 citations
TL;DR: Current microbiological and clinical evidences supporting combination therapy for CR-KP infections are revised to address some of the issues.
Abstract: The increasing incidence of carbapenem-resistant Klebsiella pneumoniae (CR-KP) fundamentally alters the management of patients at risk to be colonized or infected by such microorganisms. Owing to the limitation in efficacy and potential for toxicity of the alternative agents, many experts recommend using combination therapy instead of monotherapy in CR-KP-infected patients. However, in the absence of well-designed comparative studies, the best combination for each infection type, the continued role for carbapenems in combination therapy and when combination therapy should be started remain open questions. Herein, the authors revise current microbiological and clinical evidences supporting combination therapy for CR-KP infections to address some of these issues.
143 citations
TL;DR: Antimicrobial photodynamic therapy (aPDT) as discussed by the authors involves the combination of a nontoxic dye and low-intensity visible light which produces cytotoxic reactive oxygen species.
Abstract: Microbial biofilms are responsible for a variety of microbial infections in different parts of the body, such as urinary tract infections, catheter infections, middle-ear infections, gingivitis, caries, periodontitis, orthopedic implants, and so on. The microbial biofilm cells have properties and gene expression patterns distinct from planktonic cells, including phenotypic variations in enzymic activity, cell wall composition and surface structure, which increase the resistance to antibiotics and other antimicrobial treatments. There is consequently an urgent need for new approaches to attack biofilm-associated microorganisms, and antimicrobial photodynamic therapy (aPDT) may be a promising candidate. aPDT involves the combination of a nontoxic dye and low-intensity visible light which, in the presence of oxygen, produces cytotoxic reactive oxygen species. It has been demonstrated that many biofilms are susceptible to aPDT, particularly in dental disease. This review will focus on aspects of aPDT that are designed to increase efficiency against biofilms modalities to enhance penetration of photosensitizer into biofilm, and a combination of aPDT with biofilm-disrupting agents.
132 citations
TL;DR: The authors discuss carbapenem resistance in Acinetobacter baumannii, a bacterial isolate often implicated in nosocomial infections andTherapeutic options are exceedingly limited, relying on polymyxins in combinations with other antibiotics, with few, if any, new active agents in the pipeline.
Abstract: Unprecedented levels of antimicrobial resistance in bacterial isolates have prompted great concerns globally. In 2012 the WHO released a publication outlining the evolving threat of antimicrobial resistance in order to raise awareness and to stimulate coordinated international efforts. The carbapenem class of antibiotics is largely considered as an antibiotic of last-resort when treating infections. Now carbapenem resistance further limits treatment options. In this article the authors discuss carbapenem resistance in Acinetobacter baumannii, a bacterial isolate often implicated in nosocomial infections. Virulence factors, intrinsic and acquired resistance mechanisms, together with laboratory challenges in the detection and antibiotic susceptibility testing of A. baumannii make this a truly problematic isolate. Therapeutic options are exceedingly limited, relying on polymyxins in combinations with other antibiotics, with few, if any, new active agents in the pipeline.
124 citations
TL;DR: Clinical evidence of the major drugs utilized in combination schemes and how they should be prescribed considering pharmacokinetic/pharmacodynamic characteristics against CR GNB will be reviewed in this article.
Abstract: The emergence of resistant to carbapenems Gram-negative bacteria (CR GNB) has severely challenged antimicrobial therapy. Many CR GNB isolates are only susceptible to polymyxins; however, therapy with polymyxins and other potentially active antibiotics presents some drawbacks, which have discouraged their use in monotherapy. In this context, along with strong pre-clinical evidence of benefit in combining antimicrobials against CR GNB, the clinical use of combination therapy has been raised as an interesting strategy to overcome these potential limitations of a single agent. Polymyxins, tigecycline and even carbapenems are usually the cornerstone agents in combination schemes. Optimization of the probability to attain the pharmacokinetic/pharmacodynamic targets by both cornerstone drug and adjuvant drug is of paramount importance to achieve better clinical and microbiological outcomes. Clinical evidence of the major drugs utilized in combination schemes and how they should be prescribed considering pharmacokinetic/pharmacodynamic characteristics against CR GNB will be reviewed in this article.
123 citations
TL;DR: This review focuses on infection control strategies for identification and control of A. baumannii, as well as the available therapeutic options.
Abstract: Carbapenem-resistant Acinetobacter baumannii pose a significant threat to hospitalized patients, as therapeutic options are scarse Alarmingly, rates of carbapenem-resistance in A baumannii are on the rise and are slowly becoming a routine phenotype for this organism This review focuses on infection control strategies for identification and control of A baumannii, as well the available therapeutic options
111 citations
TL;DR: Systemic infection is often revealed by or associated with brain dysfunction, which is characterized by alteration of consciousness, ranging from delirium to coma, seizure or focal neurological signs, and is associated with increased mortality, morbidity and long-term cognitive disability.
Abstract: Sepsis is often associated with CNS dysfunction that is frequently unrecognized. This dysfunction is not due to direct infection of the CNS, so is better termed ‘sepsis-associated encephalopathy’. An altered mental status may be present in the early stage of sepsis, even preceding common clinical signs of sepsis. EEG and other neurophysiologic techniques may help to detect sub-clinical alterations and to establish clinical outcome. The pathophysiological mechanism of sepsis-associated encephalopathy is not perfectly understood and is very likely multifactorial, involving direct toxicity of microorganisms or byproducts, and the effects of inflammatory mediators, metabolic alterations, and impaired cerebral circulation. There are no specific or symptomatic treatments for sepsis-associated encephalopathy.
103 citations
TL;DR: Current evidence regarding risk factors for mortality in patients with K. pneumoniae BSI are examined, the issue of a risk prediction model for CR-KP BSI is addressed and the importance of infection source control and early appropriate antimicrobial treatment have been associated with survival.
Abstract: The dramatic increase of antibiotic resistance in Klebsiella pneumoniae has been associated with fatal outcomes. First, bloodstream infections (BSIs) caused by extended-spectrum β-lactamases (ESBL) Enterobacteriaceae have been associated with treatment failure, more recently BSIs caused by carbapenem-resistant K. pneumoniae (CR-KP) have been reported to be fatal in approximately 50% of cases. Severity of underlying disease, intensive care unit stay at infection onset, infection with ESBL or CR-KP strain and delay in administration of appropriate therapy are among the most common risk factors for mortality in patients with K. pneumoniae BSI, while infection source control and early appropriate antimicrobial treatment have been associated with survival. Thus, risk assessment for ESBL and/or CR-KP is mandatory in patients with suspicion of K. pneumoniae BSI. Here, we examine current evidence regarding risk factors for mortality in patients with K. pneumoniae BSI and address the issue of a risk prediction model for CR-KP BSI.
85 citations
TL;DR: The intrinsic and acquired resistance mechanisms of A. baumannii are presented here, with special focus on β-lactam resistance, and the most up-to-date techniques for identification, including phenotypical and molecular tests, and screening of those emerging resistance traits are highlighted.
Abstract: Acinetobacter baumannii, recognized as a serious threat in healthcare facilities, has the ability to develop resistance to antibiotics quite easily. This resistance is related to either gene acquisition (horizontal gene transfer) or mutations in the genome, leading to gene disruption, over- or down-expression of genes. The clinically relevant antibiotic resistances in A. baumannii include resistance to aminoglycosides, broad-spectrum cephalosporins, carbapenems, tigecycline and colistin, which are the last resort antibiotics. The intrinsic and acquired resistance mechanisms of A. baumannii are presented here, with special focus on β-lactam resistance. The most up-to-date techniques for identification, including phenotypical and molecular tests, and screening of those emerging resistance traits are also highlighted. The implementation of early detection and identification of multidrug-resistant A. baumannii is crucial to control their spread.
84 citations
TL;DR: The in-hospital costs attributable to multidrug resistance are alarmingly high, justifying the application of strict infection control measures in medical institutions with increased rate of MDR infections.
Abstract: This article evaluates the in-hospital costs attributable to antimicrobial multidrug resistance, defined as the difference in averaged costs of the patients infected with a multidrug-resistant (MDR) versus a non-MDR organism. PubMed and Scopus databases were searched to identify relevant studies. Twenty four studies were included: four on carbapenem-resistant or MDR Gram negative nonfermenters, eight on extended-spectrum b-lactamase-producing Enterobacteriaceae and 12 on methicillin-resistant Staphylococcus aureus. In two studies on carbapenem-resistant nonfermenters, the attributable mean hospital charges were US$58,457 and 85,299, respectively. The attributable mean total costs were US$4484 in a study referring to MDR Acinetobacter baumannii, while that varied from US$1584 to 30,093 among studies on extended-spectrum b-lactamase-producing Enterobacteriaceae. With respect to methicillin-resistant S. aureus, the attributable mean total costs varied from US$1014 to 40,090. The in-hospital costs attributable to multidrug resistance are alarmingly high, justifying the application of strict infection control measures in medical institutions with increased rate of MDR infections.
TL;DR: A more evidence-based overview of possible drug treatment regimens and their outcomes for pulmonary nontuberculous mycobacterial infections is reconstructed.
Abstract: Pulmonary disease (PD) caused by nontuberculous mycobacteria is an emerging infection mainly in countries where the incidence of tuberculosis is in decline. It affects an elderly population, often with underlying chronic lung diseases, but its epidemiology shows significant regional variation. Guidelines and recommendations for treatment of these infections exist, but build strongly on expert opinion, as very few good quality clinical trials have been performed in this field. Only for the most frequent causative agents, the Mycobacterium avium complex, Mycobacterium kansasii and Mycobacterium abscessus, a reasonable number of trials and case series is now available. For the less frequent causative agents of pulmonary nontuberculous mycobacterial (NTM) disease (Mycobacterium xenopi, Mycobacterium malmoense, Mycobacterium fortuitum, Mycobacterium chelonae) data is mostly limited to a few very small case series. Within this review, we have collected and combined evidence from all available trials and case series. From the data of these trials and case series, we reconstruct a more evidence-based overview of possible drug treatment regimens and their outcomes.
TL;DR: A comprehensive overview about schistosomiasis including recent trends in the number of people treated with praziquantel and the latest developments in diagnosis and control is presented.
Abstract: In the current era of intensified and integrated control against schistosomiasis and other neglected tropical diseases, there is a need to carefully rethink and take into consideration disease-specific issues pertaining to the diagnosis, prevention, control and local elimination. Here, we present a comprehensive overview about schistosomiasis including recent trends in the number of people treated with praziquantel and the latest developments in diagnosis and control. Particular emphasis is placed on children. Identified research needs are offered for consideration; namely, expanding our knowledge about schistosomiasis in preschool-aged children, assessing and quantifying the impact of schistosomiasis on infectious and noncommunicable diseases, developing new antischistosomal drugs and child-friendly formulations, designing and implementing setting-specific control packages and developing highly sensitive, but simple diagnostic tools that are able to detect very light infections in young children and in people living in areas targeted for schistosomiasis elimination.
TL;DR: The pharmacokinetics and pharmacodynamics (PK-PD) characteristics of voriconazole and posaconazole are reviewed and some practical recommendations how to best perform TDM in clinical practice are provided.
Abstract: Voriconazole and posaconazole are extended-spectrum triazoles recommended for treatment, prophylaxis and salvage therapy of Aspergillus diseases. Over the past decade many papers have emerged supporting the use of therapeutic drug monitoring (TDM) for azole antifungals. TDM is used to tailor the exposure of a specific drug to the individuals to optimize treatment response and minimize side effects. We reviewed the pharmacokinetics and pharmacodynamics (PK-PD) characteristics of voriconazole and posaconazole. We present the available evidence on target concentrations defining maximal efficacy and minimal toxicity. Finally we provide some practical recommendations how to best perform TDM in clinical practice.
TL;DR: The authors will review the changing approaches to sepsis diagnosis and discuss some of the markers that seem most relevant at the present time.
Abstract: Sepsis is a common and serious complication in intensive care unit patients. An important factor in optimizing survival rates in septic patients is the ability to start treatment early in the course of disease; there is, therefore, a need for accurate diagnostic tests. In recent years, there has been a move away from the rather vague and nonspecific signs that were previously used to diagnose sepsis towards the possible adjunctive role of biomarkers. Many biomarkers have been proposed and assessed clinically, but none alone is specific enough to definitively determine diagnosis. The future direction of research is most likely a greater focus on the use of panels or combinations of markers with clinical signs. Some biomarkers may also be useful for prognosis and guiding therapy. Here, the authors will review our changing approaches to sepsis diagnosis and discuss some of the markers that seem most relevant at the present time.
TL;DR: Alternative treatments are used for pregnant women, young children and those who cannot tolerate doxycycline, but quinolones, rifampin and newer macrolides may also provide some benefit.
Abstract: Q fever is caused by the bacterium Coxiella burnetii and has both acute and chronic forms. The acute disease is a febrile illness often with headache and myalgia that can be self-limiting, whereas the chronic disease typically presents as endocarditis and can be life threatening. The normal therapy for the acute disease is a 2 week course of doxycycline, whereas chronic disease requires 18–24 months of doxycycline in combination with hydroxychloroquine. Alternative treatments are used for pregnant women, young children and those who cannot tolerate doxycycline. Doxycycline resistance is rare, but has been reported. Co-trimoxazole is a currently recommended alternative treatment, but quinolones, rifampin and newer macrolides may also provide some benefit.
TL;DR: The current global status of the elimination efforts, transmission control processes and strategies for measuring impact and continuing surveillance after MDA has ceased are described.
Abstract: Lymphatic filariasis (LF) is an important public health problem endemic in 73 countries, where it is a major cause of acute and chronic morbidity and a significant impediment to socioeconomic development. It is targeted for elimination by 2020, through preventive chemotherapy using albendazole in combination with either ivermectin or diethylcarbamazine citrate. Preventive chemotherapy enables the regular and coordinated administration of safe, single-dose medications delivered through mass drug administration (MDA). Many countries are now scaling down MDA activities after achieving 100% geographic coverage and instituting monitoring and evaluation procedures to establish the impact of several consecutive rounds of MDA and determine if transmission has been interrupted. At the same time, countries yet to initiate MDA for elimination of LF will adopt improved mapping and coverage assessment protocols to accelerate the efforts for achieving global elimination by 2020. This review provides an update on treatm...
TL;DR: Current data from 43 clinical cases and results from various infection models on necrotizing pneumonia are summarized and the contribution of S. aureus PVL and a preceding influenza infection are discussed to present a concept of the pathogenesis of necrotized pneumonia.
Abstract: Only recently necrotizing pneumonia was defined as a specific disease entity that is caused by a Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus strain and is frequently preceded by an influenza infection. Necrotizing pneumonia is characterized by a sudden onset and rapid worsening of symptoms, leukopenia, airway hemorrhages, severe respiratory failure and a high mortality rate. Despite clear epidemiological data, the function of PVL in necrotizing pneumonia has been controversially discussed due to conflicting results from different disease models. Furthermore, there are many proposed mechanisms how a viral infection could facilitate and interact with a bacterial superinfection. In this review, we summarize current data from 43 clinical cases and results from various infection models on necrotizing pneumonia. We discuss the contribution of S. aureus PVL and a preceding influenza infection and present a concept of the pathogenesis of necrotizing pneumonia.
TL;DR: The genetic diversity of HIV-1 continues to increase overtime due to demographic factors such as travel and migration and frequent co/superinfections, which leads to an increasing number of drug-resistant strains, especially in resource limited countries.
Abstract: HIV-1 in humans resulted from at least four cross-species transmissions of simian immunodeficiency viruses (SIVs) from chimpanzees and gorillas in West Central Africa, while HIV-2 viruses resulted from at least eight independent transmissions of SIVs infecting sooty mangabeys in West Africa only, where one of these transmissions (HIV-1 group M) is responsible for the global epidemic. HIV-1 M is subdivided into nine subtypes and a wide diversity of circulating recombinant forms (CRFs) and unique recombinant forms. The heterogenic HIV-1 M subtype/CRF distribution is the result of founder effects. The genetic diversity of HIV-1 continues to increase overtime due to demographic factors such as travel and migration and frequent co/superinfections. In addition, the expanded access to antiretrovirals leads to an increasing number of drug-resistant strains, especially in resource limited countries.
TL;DR: Novel therapeutic approaches including CMX001, a new orally bioavailable lipid conjugate of cidofovir and the transfer of adenovirus-specific donor T cells in the context of allogeneic stem cell transplantation are discussed.
Abstract: In immunocompromised patients, human adenovirus (HAdV) infections can cause life-threatening multiorgan disease. This review summarizes the incidence and risk factors of invasive human adenovirus infections in immunocompromised patients as well as the recently developed standards for diagnostic methods and strategies according to the predominant risk factors in adults and children. Recommendations for preemptive and therapeutic treatment strategies and the outcome in different risk groups are presented. Novel therapeutic approaches including CMX001, a new orally bioavailable lipid conjugate of cidofovir and the transfer of adenovirus-specific donor T cells in the context of allogeneic stem cell transplantation are discussed.
TL;DR: Focusing limited global health resources towards dealing with the comorbidities associated with iNts disease, such as malaria and HIV infection, could be proposed as the solution to the problem of iNTS in sub-Saharan Africa.
Abstract: Despite recent high-profile articles [1–3], African invasive nontyphoidal Salmonella (iNTS) disease remains a major neglected infection responsible for large numbers of deaths across that continent. There are several reasons for this ‘neglected’ status that serve as compelling arguments to support the development of a vaccine against iNTS for Africa. By definition, neglected diseases fail to receive the level of support of better-known infectious diseases in Africa, such as HIV, malaria and tuberculosis. Consequently, progress toward a vaccine against iNTS has been slow. While Salmonella Typhi is the most common form of invasive Salmonella disease in southeast Asia, it is relatively uncommon in sub-Saharan Africa, where distinct types of iNTS dominate. Salmonella Typhimurium (and a monophasic variant that produces Phase I but not Phase II f lagella) and Salmonella Enteritidis are the most common serovars of iNTS throughout the region. Other serovars, such as Dublin and Stanleyville are found in a few percent of cases in certain countries [4]. Lacking a clear pathognomonic clinical presentation, iNTS disease most commonly kills without the patient, family or healthcare professional knowing or suspecting it. Fever is the most common clinical feature and gastrointestinal symptoms occur in under half of the patients. Indeed, a diagnosis is only possible where blood culture is available. This facility is rare in large parts of sub-Saharan Africa. A surprising clinical feature of iNTS disease is its ability to masquerade as severe pneumonia with rapid breathing. This is of concern since current empirical treatment algorithms for severe pneumonia involve therapy with penicillin, with added chloram phenicol or gentamicin for very severe pneumonia [5]. Many African isolates of iNTS are resistant to these antibiotics, particularly penicillin and chloramphenicol. In sub-Saharan Africa, high-risk hosts include young children and HIV-infected individuals, and casefatality rates in both groups are around 20–25%. By contrast, HIV infection does not appear to predispose to infection with Salmonella Typhi in those parts of Africa where typhoid fever is reported [6]. A number of clinical associations with iNTS disease in children in sub-Saharan Africa further confound diagnosis and treatment. Coinfection with iNTS and malaria can lead to the scenario where a child is successfully treated for malaria, yet dies from undiagnosed iNTS. The same can occur in children with severe anemia or malnutrition, as these are also risk factors for iNTS. In adults with HIV infection, recurrent iNTS disease has also been well documented and may arise through recrudescent or de novo infection. Focusing limited global health resources towards dealing with the comorbidities associated with iNTS disease, such as malaria and HIV infection, could be proposed as the solution to the problem of iNTS in sub-Saharan Africa. There is Invasive nontyphoidal Salmonella disease in Africa: current status
TL;DR: The authors summarize the current epidemiology, microbiology, diagnostic approach and management strategies for each type of LVADRI, and review current concepts regarding antibiotic prophylaxis for LVAD implantation.
Abstract: Left ventricular assist devices (LVAD) are increasingly being used both as a bridge to transplantation and for long-term myocardial surrogate destination therapy in patients with end-stage heart failure. Primarily owing to the presence of a driveline that connects the device to an external battery through an open skin incision, the rates of LVAD-related infections (LVADRIs) are high, ranging from 30 to 50%. LVADRIs can be broadly classified into driveline infection, pump pocket infection, bloodstream infection and endocarditis/pump or cannula infection. Diagnostic evaluation and management of these complicated infections can be quite challenging for clinicians involved in the care of these patients. Here, the authors summarize the current epidemiology, microbiology, diagnostic approach and management strategies for each type of LVADRI. The authors also review current concepts regarding antibiotic prophylaxis for LVAD implantation. Finally, the authors highlight the gaps in the knowledge of LVADRI and provide directions for future studies.
TL;DR: The laboratory tools that have been developed in this field since the discovery of the Toxoplasma gondii parasite are considered, with emphasis on the most recent tests and how they can or should be used in different clinical situations.
Abstract: The Toxoplasma gondii parasite is a worldwide threat most particularly in fetal life and immunosuppression. In most clinical situations (except in some ocular cases), correct detection or identification of toxoplasmosis requires biological analysis. This article considers the laboratory tools that have been developed in this field since the discovery of the pathogen, with emphasis on the most recent tests and how they can or should be used in different clinical situations. The authors also discuss the requirements and pitfalls that one should be aware of when biologically investigating this intriguing parasitosis.
TL;DR: In this article, a vicious cycle of hyperglycemia (≥11.1 mmol/l) or other diabetes-associated factors facilitate or worsen the development of infections and vice versa, the infections deteriorate the glycemic control of the patients.
Abstract: The vicious cycle is that hyperglycemia (≥11.1 mmol/l) or other diabetes-associated factors facilitate or worsen the development of infections and vice versa, the infections deteriorate the glycemic control of the patients. Diabetic patients are prone to some infections, infection recurrences and poor outcomes. Immunocompromised state and frequent antibiotic use are associated with antibiotic resistance of the bacterial pathogens, such as Mycobacterium tuberculosis (in some studies), methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii, bacteria in diabetic foot infections and different opportunistic and rare pathogens or multidrug-resistant strains. Prompt diagnostics and susceptibility testing, early and aggressive surgical and/or antibiotic therapy, and, importantly, good glycemic control are of utmost importance for treatment of antibiotic-resistant infections in diabetic patients.
TL;DR: Identification of asymptomatic cases, vector control and treatment of post-kala-azar dermal leishmaniasis would allow new perspectives in VL control and management.
Abstract: Human visceral leishmaniasis (VL) continues to be a life-threatening neglected tropical disease, with close to 200 million people at risk of infection globally. Epidemics and resurgence of VL are associated with negligence by the policy makers, economic decline and population movements. Control of the disease is hampered by the lack of proficient vaccination, rapid diagnosis in a field setting and severe side effects of current drug therapies. The diagnosis of VL relied largely on invasive techniques of detecting parasites in splenic and bone marrow aspirates. rK39 and PCR, despite problems related to varying sensitivities and specificities and field adaptability, respectively, are considered the best options for VL diagnosis today. No single therapy of VL currently offers satisfactory efficacy along with safety. The field of VL research only recently shifted toward actively identifying new drugs for safe and affordable treatment. Oral miltefosine and safe AmBisome along with better use of amphotericin B have been rapidly implemented in the last decade. A combination therapy will substantially reduce the required dose and duration of drug administration and reduce the chance of the development of resistance. In addition, identification of asymptomatic cases, vector control and treatment of post-kala-azar dermal leishmaniasis would allow new perspectives in VL control and management.
TL;DR: The experience and recommendations of combinational antifungal therapy for cryptococcal infections, systemic candidiasis, invasive aspergillosis and other rare mold infections have been presented, giving some information on mechanism of action and principles in combined use of mycotic anti-infectives.
Abstract: Although therapeutic first-line approaches have been established in severely immunosuppressed patients with a high risk of invasive fungal infections, treatment modalities for cases with unsatisfactory outcome have not been well defined, especially for the pediatric age gap. Therapy with coadministration of two or three antifungals has been applied by clinicians in difficult-to-treat infections, which still have no support from randomized, controlled clinical trials. The most prevailing reason for a combination regimen is to broaden the antimycotic spectrum, which may even result in antagonistic interaction. The experience and recommendations of combinational antifungal therapy for cryptococcal infections, systemic candidiasis, invasive aspergillosis and other rare mold infections have been presented in this review, giving some information on mechanism of action and principles in combined use of mycotic anti-infectives. Most experience of combination therapy approaches are in adult patients; but in fact, there is no conclusive data documenting definite benefits of this approach, either in adults or children.
TL;DR: More data on disease progression depending on conversion and reversion in IGRA is needed and a better test, which is able to distinguish recent from remote latent TB infection, would be desirable in the future.
Abstract: Healthcare workers (HCW) are a risk group for TB. Even in countries with low TB incidence, the risk of TB in HCW is elevated for a wide range of tasks in healthcare, and the prevention of nosocomial infection of HCW remains as a challenge. IFN-γ release assays (IGRA) facilitate the screening of HCW for latent TB infection. In comparison with the tuberculin skin test, the IGRA reduces the number of x-rays and the amount of chemoprevention needed. However, a borderline zone should be introduced for the interpretation of IGRA results in the serial testing of HCW. More data on disease progression depending on conversion and reversion in IGRA is needed and a better test, which is able to distinguish recent from remote latent TB infection, would be desirable in the future.
TL;DR: Clinical trials in otitis, of dogs and of human patients have provided some encouraging results and phage has potential in the treatment of antibiotic resistant infection by P. aeruginosa, but full scale clinical trials are needed.
Abstract: Phage therapy for Pseudomonas aeruginosa infections has been used for more than 50 years. Controlled investigation into its use dates from the early 1990s when positive laboratory studies of local and systemic infection were followed by clinical studies: symptomatic improvement and phage multiplication were seen in a pet dog with otitis and a human with an infected burn. Antibiotic resistance has renewed interest in this approach. There have been recent positive reports in the treatment of experimental animal infection including systemic and respiratory infections. Phages have shown promise against experimental biofilms. Two small recent clinical trials in otitis, of dogs and of human patients have provided some encouraging results. Phage has potential in the treatment of antibiotic resistant infection by P. aeruginosa. Hence, full scale clinical trials are needed.
TL;DR: Current knowledge on the severity and long-term sequelae of meningococcal disease specifically is described and should be recognized by physicians treating patients with this disease and lends support for the implementation of preventative measures such as vaccination.
Abstract: This review describes current knowledge on the severity and long-term sequelae of meningococcal disease (MD) specifically. The literature databases Medline and Embase were used by combining search terms for MD and Neisseria meningitidis with terms for severity, mortality and sequelae. Case fatality for sufferers of MD remains high, typically 5-10%, despite the best medical care. Long-term sequelae in survivors may include physical, neurological, cognitive, behavioral and psychological consequences, such as hearing loss, amputations, skin scarring and neurodevelopmental deficits. A significantly lower quality of life is seen in survivors of MD compared with unaffected controls, with detrimental effects of childhood MD continuing into adulthood. MD carries a substantial risk of long-term sequelae and mortality. This should be recognized by physicians treating patients with this disease and lends support for the implementation of preventative measures such as vaccination.
TL;DR: The usefulness of various types of blood-derived biomarkers that are currently being studied to predict the progression of Chagas disease in patients with the indeterminate form, to assess the efficacy of antiparasitic drugs and to identify early cardiac and gastrointestinal damage is reviewed.
Abstract: This article reviews the usefulness of various types of blood-derived biomarkers that are currently being studied to predict the progression of Chagas disease in patients with the indeterminate form, to assess the efficacy of antiparasitic drugs and to identify early cardiac and gastrointestinal damage. The authors used a search strategy based on MEDLINE, Cochrane Library Register for systematic review, EmBase, Global Health and LILACS databases. Out of 1716 screened articles, only 166 articles were eligible for final inclusion. The authors classified the biomarkers according to their biochemical structure and primary biological activity in four groups: i) markers of inflammation and cellular injury, ii) metabolic biomakers, iii) prothrombotic biomarkers and iv) markers derived from specific antigens of the parasite. Several potential biomarkers might have clinical potential for the detection of early cardiopathy. Such capacity is imperative in order to detect high-risk patients who require intensive monitoring and earlier therapy. Prospective studies with longer follow-ups are needed for the appraisal of biomarkers assessing clinical or microbiological cure after therapy. At the same time, studies evaluating more than one biomarker are useful to compare the efficacy among them given the lack of a recognized gold standard.