Title: The microbiological spectrum of invasive bacterial infections in Cambodian adults and implications for standard treatment guidelines.
Other Titles: Het microbiologisch spectrum van invasieve bacteriële infecties bij volwassenen in Cambodia, en de implicaties voor behandelingsrichtlijnen.
Authors: Vlieghe, Erika; S0093746
Issue Date: 10-Feb-2014
Abstract: Invasive bacterial infections, including bloodstream infections, are a major cause of morbidity and mortality around the world. In order to choose the most adequate empiric antibiotic, clinicians require information on the most frequent bacteria causing invasive infections. This information can be obtained by culturing blood from patients suspect of invasive bacterial infections (i.e. blood cultures). Given the worldwide spread of antibiotic resistance, invasive bacterial infections have become more difficult-to-treat with commonly available antibiotics. Therefore it is also important to measure resistance rates among invasive bacteria. In addition, studying the (genetic) mechanisms behind antibiotic resistance and the genetic relations between bacteria can contribute to a better understanding of how bacteria become resistant and spread among people and in the environment. In high-income settings with a sufficient number of high-quality microbiological laboratories such as Europe and Northern America, information on the presence of (resistant) bacteria is widely available through surveillance systems, based on nationwide networks of quality-assured laboratories. In low- and middle income countries such as Cambodia, well-functioning laboratories are very scarce, and essential information on the causes and resistance patterns of invasive bacterial infections is often not available.In 2007, the Institute of Tropical Medicine, Antwerp (ITM) and Sihanouk Hospital Centre of HOPE (SHCH), Phnom Penh, Cambodia, started a joint study of blood cultures taken from all adult patients who presented with fever in the hospital between 2007 and 2010. During this study period, 5714 blood culture samples were taken from 4833 patients; in 8.8 % (n = 445) of these samples we detected pathogenic bacteria. Nearly one out of four patients with a bloodstream infection died. The most common and remarkable bacteria were Escherichia coli and other Enterobacteriaceae, Salmonella enterica, Burkholderia pseudomallei, Staphylococcus aureus and Streptococcus suis; for all of which we found high resistance rates to several commonly used antibiotics. Burkholderia pseudomallei is a bacterium living in soil and water, mainly in Southeast Asia and northern Australia. It is the cause of the disease melioidosis, which presents in many different ways such as a skin, lung, bone or bloodstream infection. The bacterium has intrinsic resistance against many commonly used antibiotics and requires treatment with expensive, broad spectrum antibiotics. We described 58 patients with melioidosis in Cambodia. The disease was mainly seen in patients with diabetes mellitus and during the rainy season. More than half of the patients died, especially those with a severe condition such as a bloodstream infection (RR 6.8 (1.82-25.5) and those who received inappropriate antibiotic treatment (RR 3.5 (2.07-5.90), p < 0.001). An earlier diagnosis and the availability of effective antibiotics would be a step forward in better outcomes for these patients.Salmonella bloodstream infections can be caused by Salmonella types which infect only humans (Salmonella Typhi and Salmonella Paratyphi which cause enteric fever), or by non-typhoid Salmonella types which cause illness in animals and only occasionally in humans. Between 2007-2010 we described 72 patients with Salmonella bloodstream infections. These were caused by Salmonella types of the first group – Salmonella Typhi (20 cases) and Salmonella Paratyphi (2 cases) – and by ‘non-typhoid’ Salmonella types, most commonly Salmonella Choleraesuis (50 cases). This bacterium causes fever in pigs and occasionally in humans with very low immunity. In patients with HIV/AIDS, Salmonella Choleraesuis caused multiple episodes of fever. All Salmonella presented with high resistance rates, especially for ciprofloxacin (in Salmonella Typhi) and azithromycin (in Salmonella Choleraesuis), two important antibiotics for the treatment of enteric fever. Therefore, a review of the guidelines for enteric fever treatment is warranted.Surprisingly, between 2011 and 2013, we observed a sudden and very sharp rise in the number of infections with Salmonella Paratyphi A, mostly in the capital Phnom Penh. As this coincides with an increased number of European travelers returning from Cambodia with enteric fever, we presume a local outbreak is ongoing which warrants prompt investigation and control measures.Escherichia coli is the most common cause of (complicated) intra-abdominal and genito-urinary infections. In our study, about 50% of these bacteria were highly resistant for a combination of first and second line antibiotics, mostly due to the presence of extended spectrum beta-lactamases (ESBL). Most of these highly resistant bacteria with ESBL carried a common mechanism (i.e. CTX-M) which is spreading quickly around the world, including in Cambodia. In our study, people who had recent exposure to antibiotics were at higher risk of having a ESBL-positive Escherichia coli bloodstream infection (RR 1.46 (1.03-2.09), p = 0.035). About 30% of all patients with Escherichia coli bloodstream infection died, especially those who suffered from many other illnesses (RR 2.75 (1.11-6.81), p = 0.028) such as chronic liver disease. Remarkably, inappropriate antibiotic choices did not increase mortality significantly (RR 1.16 ( 0.66-2.06), p = 0.669), in contrast with melioidosis patients.Staphylocccus aureus is the most common cause of skin infections worldwide. Its most famous resistance type is methicillin resistance (‘MRSA’), known as a typical nosocomial pathogen, but now frequently associated with community-acquired infections as well. In our study, 23% of invasive Staphylococcus aureus infections was of the MRSA-type. Older age, superficial skin infections and recent hospital contact were risk factors for infection with MRSA. About 15% of all patients died, especially those older than 50 years of age (RR 4.27 (1.14-15.9), p = 0.044). We observed a wide variety of genetic Staphylococcus aureus-types, but five main clones dominated, including 2 types which have been found in animals as well (i.e. ST 398 and ST 9).During the study period, we observed also 13 patients with invasive Streptococcus suis infection. Streptococcus suis usually infects pigs; people can acquire the pathogen through close contact with pigs or undercooked food. These 13 patients presented with meningitis with or without bloodstream infection and often required antibiotic treatment during several weeks. All patients survived, but one third had complications such as deafness. Interestingly, we noted important similarities with Streptococcus suis isolates circulating in southern Vietnam and found resistance problems associated with antibiotic use in animals.We conclude that bloodstream infections in Cambodian adults are often associated with high mortality and high levels of complex antibiotic resistance. Therefore, several urgent measures are to be taken. To contain antibiotic resistance we suggest a wide range of actions, from an improved availability of necessary drugs, adapted treatment guidelines and hand hygiene to updated education and international collaboration.
Publication status: published
KU Leuven publication type: TH
Appears in Collections:Laboratory for Clinical Infectious and Inflammatory Disorders

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