British infection association guidelines for the diagnosis and management of enteric fever in England.

Enteric fever (EF) is an infection caused by the bacteria called Salmonella Typhi or Paratyphi. Infection is acquired through swallowing contaminated food or water. Most EF in England occurs in people returning from South Asia and other places where EF is common; catching EF in England is rare. The main symptom is fever, but stomach pain, diarrhoea, muscle aches, rash and other symptoms may occur. EF is diagnosed by culturing the bacteria from blood and/or stool in a microbiology laboratory. EF usually responds well to antibiotic treatment. Depending on how unwell the individual is, antibiotics may be administered by mouth or by injection. Over the past several years, there has been an overall increase in resistance to antibiotics used to treat enteric fever, in all endemic areas. Additionally, since 2016, there has been an ongoing outbreak of drug-resistant EF in Pakistan. This infection is called extensively drug-resistant, or XDR, EF and only responds to a limited number of antibiotics. Occasionally individuals develop complications of EF including confusion, bleeding, a hole in the gut or an infection of the bones or elsewhere. Some people may continue to carry the bacteria in their stool for a longtime following treatment for the initial illness. These people may need treatment with a longer course of antibiotics to eradicate infection. Travellers can reduce their risk of acquiring EF by following safe food and water practices and by receiving the vaccine at least a few weeks before travel. These guidelines aim to help doctors do the correct tests and treat patients for enteric fever in England but may also be useful to doctors and public health professionals in other similar countries.

Nitroimidazole-refractory giardiasis: a growing problem requiring rational solutions.

BACKGROUND: Giardia intestinalis is microaerophilic diarrhoea-causing protozoan common in countries with suboptimal sanitation. Standard treatment is with nitroimidazoles, but a growing number of refractory cases is being reported. Treatment failure has become increasingly prevalent in travellers who contract giardiasis in Asia. Clinicians are increasingly falling back on second-line and less well-known drugs to treat giardiasis. AIMS: To review nitroimidazole-refractory G. intestinalis infection, examine the current efficacy of standard therapeutic agents, consider potential resistance mechanisms which could cause treatment failure and describe the practical aspects of managing this emerging clinical problem. SOURCES: A PubMed search was conducted using combinations of the following terms: refractory, Giardia, giardiasis, resistance and treatment. Articles on the pharmacotherapy, drug resistance mechanisms and use of alternative agents in nitroimidazole-refractory giardiasis were reviewed. CONTENT: We review the standard drugs for giardiasis, including their efficacy in initial treatment, mode of action and documented in vitro and in vivo drug resistance. We assess the efficacy of alternative drugs in nitroimidazole-refractory disease. Existing data suggest a potential advantage of combination treatment. IMPLICATIONS: An optimal treatment strategy for refractory giardiasis has still to be determined, so there is no standard treatment regimen for nitroimidazole-refractory giardiasis. Further work on drug resistance mechanisms and the use of drug combinations in this condition is a priority.

Enteric fever in India: current scenario and future directions.

Enteric fever is a major cause of morbidity and mortality in tropical areas worldwide. The Indian subcontinent bears the brunt of the disease, both in terms of absolute case numbers and drug-resistant strains. Recent phylogenetic studies suggest that the multidrug-resistant clade H58 originated in India and subsequently expanded through Asia and Africa. In Africa, it caused unrecognised outbreaks in areas previously considered free of the disease. In this study, we discuss the current status of enteric fever in India, the factors preventing its control and its future directions in this rapidly developing nation.

Combination therapy for carbapenem-resistant Enterobacteriaceae: increasing evidence, unanswered questions, potential solutions.

Carbapenem-resistant Enterobacteriaceae (CRE) are associated with a high mortality rate and are an increasing problem worldwide. In this mini-review, we consider the growing number of observational studies in favour of combination therapy but highlight the absence of randomised control trials. We discuss the importance of data on minimum inhibitory concentrations (MICs), both for surveillance and for individual patient management. We examine the issues surrounding the use of carbapenems, polymyxins and tigecycline in the treatment of CRE. When and how should we be using carbapenems? Which polymyxin is best? Is tigecycline much maligned? Further studies are urgently needed to validate drug combinations, doses and ratios to maximise efficacy whilst reducing drug exposure and adverse effects.

Increased incidence of nitroimidazole-refractory giardiasis at the Hospital for Tropical Diseases, London: 2008-2013.

Giardia intestinalis is the commonest gastrointestinal protozoal pathogen worldwide, and causes acute and chronic diarrhoea with malabsorption. First-line treatment is with a nitroimidazole, with a reported efficacy rate of 89%. Failure of treatment can occur in patients with hypogammaglobulinaemia or human immunodeficiency virus (HIV), or be due to nitroimidazole-resistant organisms. There is little evidence to guide the clinical management of nitroimidazole-refractory disease. We performed a retrospective audit of nitroimidazole-refractory giardiasis in returned travellers at the Hospital for Tropical Diseases, London between 2011 and 2013. Seventy-three patients with microscopy-proven or PCR-proven giardiasis in whom nitroimidazole treatment had failed were identified, and their management was investigated. In 2008, nitroimidazole treatment failed in 15.1% of patients. This increased to 20.6% in 2011 and to 40.2% in 2013. Patient demographics remained stable during this period, as did routes of referral. Of patients with giardiasis, 39.0% had travelled to India; this rose to 69.9% in patients with nitroimidazole-refractory disease. Of the patients with refractory disease, 44.6% had HIV serological investigations performed and 36.5% had immunoglobulin levels determined. Patients with refractory disease were treated with various agents, including albendazole, nitazoxanide, and mepacrine, alone or in combination. All 20 patients who received a mepacrine-containing regimen were cured. This data shows a worrying increase in refractory disease, predominantly in travellers from India, which is likely to represent increasing nitroimidazole resistance. Improved tools for the diagnosis of resistant G. intestinalis are urgently needed to establish the true prevalence of nitroimidazole-resistant giardiasis, together with clinical trials to establish the most effective second-line agent for empirical treatment regimens.