Australian Group on Antimicrobial Resistance Australian Enterobacteriaceae Sepsis Outcome Programme annual report, 2014.

The Australian Group on Antimicrobial Resistance performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric Gram-negative pathogens. The 2014 survey was the second year to focus on blood stream infections. During 2014, 5,798 Enterobacteriaceae species isolates were tested using commercial automated methods (Vitek 2, BioMérieux; Phoenix, BD) and results were analysed using the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (January 2015). Of the key resistances, non-susceptibility to the third-generation cephalosporin, ceftriaxone, was found in 9.0%/9.0% of Escherichia coli (CLSI/EUCAST criteria) and 7.8%/7.8% of Klebsiella pneumoniae, and 8.0%/8.0% K. oxytoca. Non-susceptibility rates to ciprofloxacin were 10.4%/11.6% for E. coli, 5.0%/7.7% for K. pneumoniae, 0.4%/0.4% for K. oxytoca, and 3.5%/6.5% in Enterobacter cloacae. Resistance rates to piperacillin-tazobactam were 3.2%/6.8%, 4.8%/7.2%, 11.1%/11.5%, and 19.0%/24.7% for the same 4 species respectively. Fourteen isolates were shown to harbour a carbapenemase gene, 7 blaIMP-4, 3 blaKPC-2, 3 blaVIM-1, 1 blaNDM-4, and 1 blaOXA-181-lke.

The changing epidemiology of bacteraemic osteoarticular infections in the early 21st century.

Osteoarticular infections (OAI), which are often associated with bacteraemia, seem to be increasing. We studied all patients with bacteraemia and concomitant OAI: septic arthritis (SA), vertebral osteomyelitis (VOM) or peripheral osteomyelitis (POM), which were seen at our institution (1985-2011). Data were extracted from a prospective protocol of bacteraemia cases recorded. Trends in main findings were considered in five periods. Major antibiotic resistance patterns were studied. A total of 601 cases of bacteraemic OAI, accounting for 1.8% of total bactaeremias, were studied: SA (48%), VOM (40%) and POM (17%). When comparing the 1985-91 and 2007-11 periods, the incidence of bacteraemic OAI increased from 2.34 to 5.78 episodes/100 000 inhabitants per year (p <0.001); and nosocomial and healthcare-related cases increased from 18% to 30% (p <0.001) and from 10% to 25% (p <0.001), respectively. Also, there was an increase of age (median, from 49 to 65 years, p <0.001), patients with comorbidities (23% to 59%, p <0.001), and device-related OAI (7% to 28%, p <0.001). Patterns of OAI were changing over time. Compared with younger patients, older adults (≥ 65 years) had more VOM, prosthetic-joint infections and enterococcal OAI. The percentage of OAI caused by methicillin-susceptible Staphylococcus aureus decreased, while those caused by methicillin-resistant S. aureus, streptococci, enterococci, and Gram-negative bacilli increased. There was a link between certain microorganisms with specific OAI and age of patients. Over the past three decades, bacteraemic OAI increased in association with aging and use of orthopaedic devices. Nosocomial and healthcare-related OAI increased, with a rise in multidrug-resistant bacteria. These trends should be considered when planning diagnostic and therapeutic guidelines for OAI.

Bacteria and vampirism in cinema.

A vampire is a non-dead and non-alive chimerical creature, which, according to various folklores and popular superstitions, feeds on blood of the living to draw vital force. Vampires do not reproduce by copulation, but by bite. Vampirism is thus similar to a contagious disease contracted by intravascular inoculation with a suspected microbial origin. In several vampire films, two real bacteria were staged, better integrated than others in popular imagination: Yersinia pestis and Treponema pallidum. Bacillus vampiris was created for science-fiction. These films are attempts to better define humans through one of their greatest fears: infectious disease.

Host innate immune responses to microbial pathogens.

Sepsis is among the leading causes of death worldwide and its incidence is increasing. Defined as the host response to infection, sepsis is a clinical syndrome considered to be the expression of a dysregulated immune reaction induced by danger signals that may lead to organ failure and death. Remarkable progresses have been made in our understanding of the molecular basis of host defenses in recent years. The host defense response is initiated by innate immune sensors of danger signals designated under the collective name of pattern-recognition receptors. Members of the family of microbial sensors include the complement system, the Toll-like receptors, the nucleotide-binding oligomerization domainlike receptors, the RIG-I-like helicases and the C-type lectin receptors. Ligand-activated pattern-recognition receptors kick off a cascade of intracellular events resulting in the expression of co-stimulatory molecules and release of effector molecules playing a fundamental role in the initiation of the innate and adaptive immune responses. Fine tuning of proinflammatory and anti-inflammatory reactions is critical for keeping the innate immune response in check. Overwhelming or dysregulated responses induced by infectious stimuli may have dramatic consequences for the host as shown by the profound derangements observed in sepsis. Unfortunately, translational research approaches aimed at the development of therapies targeting newly identified innate immune pathways have not held their promises. Indeed, all recent clinical investigations of adjunctive anti-sepsis treatments had little, if any, impact on morbidity and all-cause mortality of sepsis. Dissecting the mechanisms underlying the transition from infection to sepsis is essential for solving the sepsis enigma. Important components of the puzzle have already been identified, but the hunt must go on in the laboratory and at the bedside.

[The death of Goffredo Mameli in 1849]. / La morte di Goffredo Mameli a Roma nel 1849.

After the introduction of firearms, which became increasingly efficient over time, the number of seriously injured soldiers increased considerably during the nineteenth century. As a consequence, surgeons were called upon to broaden their activity, performing operations which had hitherto been considered too hazardous, since they were deemed to be too extensive, or were contraindicated by the risk of complications during surgery (haemorrhage, heart and circulatory failure). From 1846 onwards, the introduction of anaesthetic techniques carried out with ether had expanded surgical perspectives in anatomical districts like the abdomen, which were previously considered a sort of taboo, such that few surgeons ventured into the realm of this internal surgery. In the mid nineteenth century the possibility of suffering from severe infections, as an immediate complication after a firearm injury or after surgical intervention, was very high, ranging between 23% in London, up to 80% in Munich, according to the available records; in Zurich a 46% mortality is reported, and a similar 43% rate came from Edinburgh. The situation worsened during war time, since injured soldiers were recovered in extremely precarious conditions, ad hoc hospitals were located in dilapidated old buildings, and the physicians and health care providers were unaware of the minimum hygiene conditions required, and performed both operations and medications without taking sterility measures into consideration. The author reports and comments on the most significant parts on the documents written by Agostino Bertani, who described in full detail the clinical evolution of the wound suffered by Goffredo Mameli, the poet and patriot of the Italian Risorgimento who wrote the Italian national anthem. The clinical evolution of Mameli's disease was unfavourable: he underwent amputation of the left lower limb after the firearm injury suffered during the defence of the Roman Republic, since a gangrenous complication had become apparent. The poet died of septicaemia on July 6, 1849, 17 days after the surgical operation.

Listerine: past, present and future--a test of thyme.

Listerine, a mouthrinse composed of a mixture of essential oils, was created in 1879 and was originally formulated as a surgical antiseptic. In spite of its known antimicrobial properties it was thought of as a product in search of a use and promoted as a deterrent for halitosis and as a floor cleaner. In the last several years Listerine has emerged as a bona fide therapeutic agent for reduction of plaque induced oral diseases. In contrast to the inconsistent history of Listerine, systemic antibiotics discovered in the 1940's were heralded as miracle drugs. However, the value of prophylactic usage of antibiotics has come under scrutiny as a result of increasing resistance and adverse reactions. Moreover, reports by both American and British professional societies have led to a re-evaluation of the relative risks associated with plaque induced bacteremia when twice-yearly visits to dental professionals are compared to daily activities. These new recommendations and revelations open the door for local antimicrobial approaches to reduce the challenge of plaque-induced bacteremias. These issues will be discussed in the context of Listerine, its intricate and complicated past, and its connection to current uses in oral health and beyond.

Emergence and disappearance of a virulent clone of Haemophilus influenzae biogroup aegyptius, cause of Brazilian purpuric fever.

SUMMARY: In 1984, children presented to the emergency department of a hospital in the small town of Promissão, São Paulo State, Brazil, with an acute febrile illness that rapidly progressed to death. Local clinicians and public health officials recognized that these children had an unusual illness, which led to outbreak investigations conducted by Brazilian health officials in collaboration with the U.S. Centers for Disease Control and Prevention. The studies that followed are an excellent example of the coordinated and parallel studies that are used to investigate outbreaks of a new disease, which became known as Brazilian purpuric fever (BPF). In the first outbreak investigation, a case-control study confirmed an association between BPF and antecedent conjunctivitis but the etiology of the disease could not be determined. In a subsequent outbreak, children with BPF were found to have bacteremia caused by Haemophilus influenzae biogroup aegyptius (H. aegyptius), an organism previously known mainly to cause self-limited purulent conjunctivitis. Molecular characterization of blood and other isolates demonstrated the clonal nature of the H. aegyptius strains that caused BPF, which were genetically distant from the diverse strains that cause only conjunctivitis. This led to an intense effort to identify the factors causing the unusual invasiveness of the BPF clone, which has yet to definitively identify the virulence factor or factors involved. After a series of outbreaks and sporadic cases through 1993, no additional cases of BPF have been reported.

The evolution of methicillin resistance in Staphylococcus aureus: similarity of genetic backgrounds in historically early methicillin-susceptible and -resistant isolates and contemporary epidemic clones.

The key genetic component of methicillin resistance, the mecA determinant, is not native to Staphylococcus aureus. Thus, the evolution of methicillin-resistant S. aureus (MRSA) must have begun with the acquisition of the mecA determinant from an unknown heterologous source some time before the first reported appearance of MRSA isolates in clinical specimens in the U.K. and Denmark (in the early 1960s). We compared the genetic backgrounds and phenotypes of a group of methicillin-susceptible S. aureus (MSSA) isolates to the properties of MRSA strains isolated in Denmark and the U.K. during the same time period, and also to the genetic profiles of contemporary epidemic clones of MRSA. All early MRSA isolates resembled a large group of the early MSSA blood isolates in phenotypic and genetic properties, including phage group, antibiotype (resistance to penicillin, streptomycin, and tetracycline), pulsed-field gel electrophoresis pattern, and spaA type and multilocus sequence type, strongly suggesting that the early MSSA examined here represented the progeny of a strain that served as one of the first S. aureus recipients of the methicillin-resistance determinant in Europe. The genetic background of this group of early MSSA isolates was also very similar to that of the widely disseminated contemporary "Iberian clone" of MRSA, suggesting that genetic determinants present in early MSSA and essential for some aspects of the epidemicity and/or virulence of these strains may have been retained by this highly successful contemporary MRSA lineage.

Molecular evidence of bacteremia by gastrointestinal pathogenic bacteria in an infant mummy from ancient Egypt.

In this study, we describe an infant mummy from ancient Egypt that showed macromorphologic signs of chronic anemia and vitamin C deficiency. From this infant, we have obtained a sterile sample from a metatarsal bone to extract ancient bacterial DNA. Following polymerase chain reaction amplification and subcloning of the amplicons, the sequence of the 16S ribosomal DNA was determined in several resulting clones. The presence of pathogenic and apathogenic bacteria, such as Escherichia coli, are indicated by our result, providing evidence of bacteremia, which probably contributed to death due to septicemia. These findings suggest that the infant, who already had chronic anemia and vitamin C deficiency, acquired a gastrointestinal infection, which finally led to a systemic spread. To our knowledge, this is the first case identifying potentially septicemic bacterial dissemination in an ancient Egyptian mummy. Using our approach, we hope to investigate distinct paleomicrobiological aspects of ancient populations, which will potentially enlighten our understanding of the development and evolution of pathogenic bacteria.

Goethe almost died of urosepsis.

In the year of 1805, Goethe almost died of urosepsis. His urological problems were not diseases arising from full health but a new variation in a life accompanied by illnesses. Some sources date the first colics he experienced to the year 1795 and others say 1805. The most dramatic period in the course of his illness was in February, when he suffered from fever of such an extent that one could speak of urosepsis. Recovery took place slowly and was accompanied by minor relapses. Nothing about this is written down in his work. On the advice of his doctors, Goethe undertook a cure in Lauchstädt in July and August. The report of his consultant, Professor Johann Christian Reil, on his problems in the field of urology remained undiscovered until 1937. Professor Reil recommended treatment with thermae carolinae, aqua calcis, soap soda crystallisata, herbae subastringentes, and uva ursi, among other measures. With increasing age, Goethe's colics disappeared. The passing of a stone has never been described. Whereas Goethe hinted about medical problem other than those reported herein, the urological problems discussed in this article were left unmentioned. Nonetheless, literature that deals with Goethe's diseases is interesting from the aspect of both the history of medicine and the history of culture.

Introduction of new technology into critical care practice: a history of HA-1A human monoclonal antibody against endotoxin.

OBJECTIVES: HA-1A, a monoclonal antibody against endotoxin, was thought to be effective in treating patients with Gram-negative sepsis. Because of this possibility, many clinicians felt obligated to use the drug and assumed that its product license application would be approved by the U.S. Food and Drug Administration (FDA). Nevertheless, the efficacy of HA-1A was not conclusively demonstrated by a first clinical trial. The FDA rejected the product license application and requested a second clinical trial, which was suspended after excess mortality was noted in patients treated with HA-1A. This review of the history of the drug was prepared to provide clinicians and sepsis investigators with information about HA-1A and, by extension, the process by which new technology is introduced into critical care practice. DATA SOURCES: Data used to prepare this review were obtained from the author's personal files as well as the computerized MEDLINE database. STUDY SELECTION: Studies were selected for their relevance to the history of HA-1A and their relevance to the introduction of potentially useful medical technology. DATA EXTRACTION: The author extracted all applicable data. DATA SYNTHESIS: Although the first clinical trial of HA-1A suggested that the drug was effective in treating patients with Gram-negative bacteremia with or without shock, further analysis by the FDA indicated a benefit only for bacteremic patients with shock. Furthermore, the original study design was not followed, leading in part to the FDA's refusal of the product license application. Concern also was raised over the issue of identifying which patients should receive HA-1A and the cost of the drug, which would have put it past the reach of some American hospitals and thereby, would have conflicted with the ethical principle of social justice. Finally, the second trial suggested that HA-1A might be harmful. CONCLUSIONS: Due to the FDA's action, the issues raised about HA-1A, and the results of the two clinical trials, clinicians should not use the drug. The history of HA-1A provides insights about how new technology is and will be introduced into critical care practice.

The medical history and death of Mozart.

The medical history and final illness of Mozart are reviewed in the light of information provided by the letters of the composer and his family. Early in his life there is no doubt that he suffered from a series of infective diseases which were common in 18th century Europe, and died of an acute epidemic illness. There is no clinical evidence for the widespread belief that his last years were dogged by chronic disease and that he died in renal failure.