Clinical Features Of Infection Research Articles

Navigating the Zika panic.

The epidemics of Ebola virus in West Africa and Zika virus in America highlight how viruses can explosively emerge into new territories. These epidemics also exposed how unprepared we are to handle infectious disease emergencies. This is also true when we consider hypothesized new clinical features of infection, such as the associations between Zika virus infection and severe neurological disease, including microcephaly and Guillain-Barré syndrome. On the surface, these pathologies appear to be new features of Zika virus infection, however, causal relationships have not yet been established. Decades of limited Zika virus research are making us scramble to determine the true drivers behind the epidemic, often at the expense of over-speculation without credible evidence. Here we review the literature and find no conclusive evidence at this time for significant biological differences between the American Zika virus strains and those circulating elsewhere. Rather, the epidemic scale in the Americas may be facilitated by an abnormally warm climate, dense human and mosquito populations, and previous exposure to other viruses. Severe disease associated with Zika virus may therefore not be a new trait for the virus, rather it may have been overlooked due to previously small outbreaks. Much of the recent panic regarding Zika virus has been about the Olympics in Brazil. We do not find any substantial evidence that the Olympics will result in a significant number of new Zika virus infections (~10 predicted) or that the Olympics will promote further epidemic spread over what is already expected. The Zika virus epidemic in the Americas is a serious situation and decisions based on solid scientific evidence - not hyped media speculations - are required for effective outbreak response.

Differences in Genotype, Clinical Features, and Inflammatory Potential of Borrelia burgdorferi sensu stricto Strains from Europe and the United States.

Borrelia burgdorferi sensu stricto isolates from patients with erythema migrans in Europe and the United States were compared by genotype, clinical features of infection, and inflammatory potential. Analysis of outer surface protein C and multilocus sequence typing showed that strains from these 2 regions represent distinct genotypes. Clinical features of infection with B. burgdorferi in Slovenia were similar to infection with B. afzelii or B. garinii, the other 2 Borrelia spp. that cause disease in Europe, whereas B. burgdorferi strains from the United States were associated with more severe disease. Moreover, B. burgdorferi strains from the United States induced peripheral blood mononuclear cells to secrete higher levels of cytokines and chemokines associated with innate and Th1-adaptive immune responses, whereas strains from Europe induced greater Th17-associated responses. Thus, strains of the same B. burgdorferi species from Europe and the United States represent distinct clonal lineages that vary in virulence and inflammatory potential.

Prevalence and Antimicrobial Susceptibility of GenitalMycoplasmataceaein Korean Women: Correlation between Phenotypic Test and Resistance Genes

Background: While 7.6% of cultured genital Mycoplasmataceae was identified as Ureaplasma urealyticum, most of them were Ureaplasma parvum (80.3%). This is the first study differentiating between these two species. We investigated the prevalence and antimicrobial resistance of genital Mycoplasmataceae in Korean women. Methods: A total of 150 specimens submitted to the laboratory for culture of M. hominis and Ureaplasma spp. were included. Detection and antimicrobial susceptibility tests were performed with the Mycoplasma IST2 kit (bioMerieux, France). The identification of Ureaplasma spp. was performed by PCR, and mutations in drug resistance genes were investigated by PCR and sequencing. Results: In total, 66 specimens (44.0%) were positive for genital Mycoplasmatacea: U. parvum, 53 (80.3%); U. urealyticum, 5 (7.6%); M. hominis, 2 (3.0%); mixed infection, 6 (9.1%). Susceptibilities of Ureaplasma spp. to erythromycin, azithromycin, clarithromycin, and doxycycline were 86.0%, 80.7%, 98.2%, and 94.7%, respectively. The susceptibility of Ureaplasma spp. to ofloxacin and ciprofloxacin was 47.4% and 17.5%, respectively. The S83L mutation was found in the ParC subunit of the ofloxacin-resistant (5/7, 71.4%) and the ciprofloxacin-resistant isolates (7/14, 50.0%). One M. hominis isolate showed resistance to erythromycin, azithromycin, and clarithromycin but susceptibility to josamycin, pristinamycin, fluoroquinolones, and tetracyclines. Conclusion: The prevalence of genital Mycoplasmataceae in Korean women was 44.0%; most of them were identified as U. parvum. As more than 10% of Ureaplasma spp. showed non-susceptibility to erythromycin and azithromycin (15.5%, 20.7%), a susceptibility test is needed prior to use of these antibiotics. Further study is needed about the clinical features of infections caused by U. urealyticum vs. U. parvum and their associated resistance mechanisms. (Ann Clin Microbiol 2016;19:13-19)

Clinical Characteristics of Group D Streptococcal Bacteremia in a University Hospital in Thailand

Materials and Methods Conclusions Acknowledgements • Background: Group D streptococci (GDS) are indigenous in the gastrointestinal tracts of humans and animals. Currently, S. bovis, the most common GDS, has been re-classified into 4 different species (Streptococcus gallolyticus, Streptococcus pasteurianus, Streptococcus infantarius and Streptococcus lutetiensis). However, clinical characteristics and the association between gastrointestinal diseases and these species have not been well studied. The objective of this study is to investigate the clinical characteristics of patients with GDS bacteremia. • Methods: We conducted a retrospective review of adult patients with GDS bacteremia who were hospitalized at Siriraj Hospital between 1 January 2009 and 30 June 2011. Clinical characteristics including predisposing factors and microbiological data were analyzed. • Results: One hundred and forty-seven episodes of bacteremia caused by GDS were included. Seventy-eight patients (58.2%) were male. Patients’ mean age was 63 years. Of 147 GDS isolates, 134 (91.2%) were identified as S. pasteurianus, 6 (4.1%) were S. gallolyticus, 2 (1.4%) were S. infantarius, 1 (0.7%) was S. lutetiensis and 4 isolates (2.7%) were unidentifiable. Cirrhosis was identified as underlying disease in 87 patients (59.2%). Eighty-three patients (56.5%) had primary bacteremia and 49 patients (33.3%) had secondary bacteremia from spontaneous bacterial peritonitis. Thirty patients (20.9%) underwent colonic evaluation and colonic polyps were the most common finding found in 8 patients. Colonic cancer was diagnosed in 5 patients with GDS bacteremia in which 4 of 5 patients were diagnosed previously and before the bacteremic episodes. Bacteremia due to S. pasteurianus was associated with patients who had cirrhosis (p = 0.041), whereas S. gallolyticus was more likely to be associated with non-cirrhotic patients (p = 0.031). Overall mortality of patients with GDS bacteremia was 22%. • Conclusion: S. pasteurianus was the most common species isolated in patients with GDS bacteremia and is associated with chronic liver disease. • Group D streptococci (GDS) are indigenous in the gastrointestinal tracts of humans and animals. The association between bacteremia caused by Streptococcus bovis (the most common species of GDS) and colonic malignancies has been documented. Currently, S. bovis has been re-classified into 4 different species (Streptococcus gallolyticus, Streptococcus pasteurianus, Streptococcus infantarius and Streptococcus lutetiensis). The prevalence and clinical characteristics of infections caused by different GDS species and the association between gastrointestinal lesions and those species has not been well studied. • S. pasteurianus was the most common species isolated in patients with GDS bacteremia. GDS infection was significantly associated with liver diseases including cirrhosis and hepatocellular carcinoma. S. pasteurianus is likely to be linked to colon cancer, especially in those without chronic liver diseases. Our study suggested that patients with S. pasteurianus bacteremia who do not have cirrhosis should be appointed for colonic evaluation and considered to search for endocarditis. Finally, beta-lactam antibiotic, especially penicillin, should be used as a drug of first choice for treatment of GDS bacteremia. • We thank the staffs of Department of Microbiology for their collaborations and Ms. Khemajira Karaketklang, Department of Medicine, Siriraj Hospital for assistance of data analysis. Poster number 831

The Distribution, Drug Resistance, and Clinical Characteristics of Acinetobacter baumannii Infections in Solid Organ Transplant Recipients

ObjectiveAcinetobacter baumannii has become a major problem among solid organ transplant (SOT) recipients. The aim of this study was to investigate the distribution, drug resistance, and clinical characteristics of A baumannii infections in SOT recipients. MethodsWe retrospectively identified 78/1,850 (4.2%) SOT recipients who developed A baumannii infections from January 1, 2003, to April 1, 2015, and evaluated the distribution, drug resistance, and clinical characteristics of these infections. ResultsOver the study period, 101 episodes of A baumannii infection occurred in 78 SOT recipients, with respiratory tract (37.6%) and blood (35.6%) as the most common sites of infection. Fifty-six episodes of A baumannii infection were accompanied with a serum creatinine level of >1.5 mg/dL. Multidrug resistance (MDR) or extensive drug resistance (XDR) occurred in 83.2%. Antibiotic resistance rate of all A baumannii to 8 of 9 antibiotics investigated was >50%. Seventy-eight percent of A baumannii were carbapenem-resistant. All but one A baumannii isolates tested against polymyxin B were susceptible. There were 40 (51.3%) overall in-hospital deaths and 31 (39.7%) infection-related deaths. ConclusionsA baumannii infections are associated with high morbidity and mortality in SOT recipients, and MDR or XDR is common. Prevention measures are essential, and combination therapy of antibiotics are needed to improve the outcomes of SOT recipients with A baumannii infections.

Culture independent bacterial identification in post-mortem samples

Investigation of post-mortem samples for a bacterial aetiology is challenging. There may be pathological signs of inflammation and infection, but not always. Further complications arise via detection of organisms derived from agonal or post-mortem translocation from the colonised mucous membranes and contamination artificially introduced by collection processes. Attributing a terminal outcome to the finding of specific bacteria ranges from high certainty for pathogens not associated with the human microbiome, to low certainty when observing mixed bacterial species including normal flora. Clinical features of infection, known individual risk factors, particular bacterial virulence genes, and case histories are important pieces of the puzzle. Treatment with antimicrobials, peculiar nutritional and atmospheric requirements of bacteria, and delays in sample collection can all reduce the ability of traditional culture methods to recover causative organisms. In those circumstances recovery and specific identification of bacterial DNA has been an effective diagnostic augmentation for post-mortem bacteriology. Use of DNA encoding the bacterial ribosomes has been the primary culture independent approach. This technique will be discussed and local cases will be presented. The diagnostic value of 2 nd and 3 rd generation DNA sequencing instrument output and resultant bioinformatically reconstructed microbial genome content from clinical samples will be discussed.

Niacin metabolism and indoleamine 2,3-dioxygenase activation in malnourished patients with flaky paint dermatosis

Flaky paint dermatosis, characterized by extensive, often bilateral areas of flaking and pigmentation, mostly in sun unexposed areas is considered a feature of kwashiorkor in both children and adults, and must be differentiated from other dermatosis, including chapped and xerotica skin, and pellagra. In this case series we provide evidence that malnourished patients with flaky paint dermatosis and infection/inflammation shown laboratory data suggestive of indoleamine 2,3-dioxygenase (IDO) activation, besides decreased urinary excretion of N1-methylnicotinamide (N1 MN), a marker of pellagra.We study nine adult patients showing flaky paint dermatosis and clinical features of infection or inflammation, and increased serum C-reactive protein, characteristic of the presence of acute phase response syndrome. As a group, they had low or deficient urinary N1 MN excretion (0.52 ± 0.39 mg/g creatinine) compatible with pellagra. They also showed low serum tryptophan levels (<29 μmol/L) and a serum kynurenine/tryptophan ratio higher than 0.04, suggesting increased IDO expression and increase in the tryptophan oxidation.Findings suggest that some patients with flaky paint dermatosis showed laboratory data suggestive of IDO activation, besides decreased N1 MN urinary excretion. Taken together, the data support the idea that flaky paint dermatosis could be a skin manifestation of niacin deficiency.

Nocardiosis in 132 patients with cancer: microbiological and clinical analyses.

To correlate the microbiological and clinical features of infections caused by Nocardia species. We determined the species and drug susceptibility of 138 Nocardia strains isolated from 132 patients at the University of Texas M. D. Anderson Cancer Center (Houston, TX) from 2002 through 2012 and analyzed the clinical features. The 132 patients included 82 men and 50 women with a mean age of 59.1 years. All except two had underlying cancer, and 47 (35.6%) also received a stem cell transplant. These patients experienced 136 episodes of Nocardia infection, including pulmonary infection, abscess of deep skin and soft tissue, bacteremia and dissemination, and brain abscess. The 138 Nocardia strains involved 27 species, of which 20 species have been described since 2000. Common species included Nocardia nova, Nocardia cyriacigeorgica, Nocardia farcinica, and Nocardia abscessus, together accounting for 59.4%. N nova caused most bacteremia cases, whereas N farcinica caused most of the skin and brain infections. Infections with a few recent species likely represented first confirmation or report of human infections. Antimicrobial susceptibility tests of 117 strains showed that they were all susceptible to trimethoprim-sulfamethoxazole and linezolid but variably susceptible to other drugs depending on species. Most patients who were treated for the infection showed improvement or resolution. Diverse Nocardia species can cause secondary infections in patients with cancer. Timely species identification and antimicrobial susceptibility tests may guide treatment.

Prevalence and features of pathogenic bacteria in the department of hematology without bone marrow transplantation in Peking Union Medical College Hospital from 2010 to 2012

To investigate the incidence, pathogens, and clinical features of infection in consecutive cases from 2010 to 2012 in Peking Union Medical College Hospital. The incidence, pathogen, treatment, and outcomes of patients with hematological diseases who had positive findings of bacterium in their samples from 2010 to 2012 were retrospectively analyzed. There were 449 positive samples (5.8%) from 4 890 patients during this period, among which 388 were proved to be with pathogenic bacteria. Samples separated from patients with community-aquired infections accounted for 8.4% of all positive samples. Most community-aquired infections were caused by Gram-negative bacteria (75%), although no multidrug-resistant bacteria was observed. Samples separated from patients with nosocomial infections accounted for 91.6% of all positive samples. Respiratory tract (49.4%) and peripheral blood (32.6%) were the most common samples with positive results. Skin soft tissues (10.4%), and urine (3.7%) were less common samples. Most of the pathogenic bacteria of the nosocomial infections were Gram-negative (66.9%). The most common Gram-negative bacteria included Escherichia coli (13.8%), Pseudomonas aeruginosa (12.1%), and Klebsiella pneumonia (12.1%), while Staphylococcus aureus (10.4%), Enterococcus faecium (7.0%), and Staphylococcus epidermidis (5.1%) were the most common Gram-positive bacteria. Gram-negative bacteria consisted of most of sputum samples and peripheral blood samples. Samples from the surface of skin wound and anal swab were composed largely by Gram-positive bacteria (63.8%). The detection rates of extended-spectrum beta-lactamase-producing Klebsiella pneumonia/Klebsiella oxytoca, Escherichia coli, and Proteus mirabilis were 24.0%, 87.9% and 38.4%, respectively. The resistance to Acinetobacter baumannii was serious. Multidrug-resistant, extensive drug resistant and pan drug resistant A. baumannii acountted for 74% of all A. Baumannii infections. Stenotrophomonas maltophilia showed low resistance to sulfamethoxazole/trimethoprim, levofloxacin and minocycline. Also, 22 methicillin-resistant Staphylococcus aureus and 9 methicillin-resistant Staphylococcus Epidermidis were detected, which were only sensitive to vancomycin, teicoplanin, and linezolid. All patients were treated in the haematology wards and most of them were under agranulocytosis or immunosuppression. Finally, 22 patients reached clinical recovery through anti-infective therapy, whereas 49 patients died. Among those deaths, 42 patients attributed to severe infections and infection-associated complications. Fourteen of all the deaths might be infected with drug-resistance bacteria. There were 61 samples proved to be bacteria colonization. Nonfermenters such as Acinetobacter baumannii and Stenotrophomonas maltophilia made up for a large amount of bacteria colonization. The pathogens of nosocomial infections in the hematology ward are mainly Gram-negative bacteria. The incidences and pathogens vary from different infection sites. Nosocomial infection still has a higher mortality rate. Once nonfermenters are detected positive, the pathogenic or colonial bacteria should be distinguished.

Viraemic frequencies and seroprevalence of non-primate hepacivirus and equine pegiviruses in horses and other mammalian species.

Non-primate hepacivirus (NPHV), equine pegivirus (EPgV) and Theiler's disease associated virus (TDAV) are newly discovered members of two genera in the Flaviviridae family, Hepacivirus and Pegivirus respectively, that include human hepatitis C virus (HCV) and human pegivirus (HPgV). To investigate their epidemiology, persistence and clinical features of infection, large cohorts of horses and other mammalian species were screened for NPHV, EPgV and TDAV viraemia and for past exposure through serological assays for NPHV and EPgV-specific antibodies. NPHV antibodies were detected in 43% of 328 horses screened for antibodies to NS3 and core antibodies, of which three were viraemic by PCR. All five horses that were stablemates of a viraemic horse were seropositive, as was a dog on the same farm. With this single exception, all other species were negative for NPHV antibodies and viraemia: donkeys (n=100), dogs (n=112), cats (n=131), non-human primates (n=164) and humans (n=362). EPgV antibodies to NS3 were detected in 66.5% of horses, including 10 of the 12 horses that had EPgV viraemia. All donkey samples were negative for EPgV antibody and RNA. All horse and donkey samples were negative for TDAV RNA. By comparing viraemia frequencies in horses with and without liver disease, no evidence was obtained that supported an association between active NPHV and EPgV infections with hepatopathy. The study demonstrates that NPHV and EPgV infections are widespread and enzootic in the study horse population and confirms that NPHV and potentially EPgV have higher frequencies of viral clearance than HCV and HPgV infections in humans.

THE MODERN CONCEPTIONS ABOUT IMMUNOPATHOGENESIS OF INFECTION CAUSED BY THE EPSTEIN–BARR VIRUS

Abstract. The current review summarizes modern data about structural and functional organization of the Epstein–Barr virus (EBV) and stages of its reproduction. The information concerning immune pathogenesis and clinical features of infection caused by EBV and EBV-associated diseases is presented in the article.

Current developments in understanding of West Nile virus central nervous system disease.

West Nile virus (WNV) is the most important cause of epidemic encephalitis in the United States. We review articles published in the last 18 months related to the epidemiology, immunology, clinical features, and treatment of this disease. There was a resurgence in WNV disease in the United States in 2012. The WNV strain now predominant in the United States (NA/WN02) differs from the initial emergent isolate in 1999 (NY99). However, differences in the genetics of currently circulating United States WNV strains do not explain variations in epidemic magnitude or disease severity. Innate and acquired immunity are critical in control of WNV, and in some cases pathways are central nervous system specific. The clinical features of infection are now well understood, although nonconfirmed observations of chronic viral excretion in urine remain controversial. There is no specific antiviral therapy for WNV, but studies of antivirals specific for other flaviviruses may identify agents with promise against WNV. Phase I and II human WNV vaccine clinical trials have established that well tolerated and immunogenic WNV vaccines can be developed. WNV remains an important public health problem. Although recent studies have significantly increased our understanding of host immune and genetic factors involved in control of WNV infection, no specific therapy is yet available. Development of a well tolerated, immunogenic, and effective vaccine against WNV is almost certainly feasible, but economic factors and the lack of predictability of the magnitude and location of outbreaks are problematic for designing phase III trials and ultimate licensure.

G381(P) Bilateral Pulmonary Consolidation Associated with Chronic Recurrent Multifocal Osteomyelitis

AimsA nine-year-old girl with Chronic Recurrent Multifocal Osteomyelitis (CRMO) developed asymptomatic bilateral pulmonary consolidation that was thought to be part of the CRMO disease process. Approximately 25% of patients with...

Dengue Fever and International Travel

Dengue is a leading public health problem with an expanding global burden. Dengue virus is also a significant cause of illness in international travelers with an increasing number of cases of dengue fever identified in travelers returning from dengue-endemic countries. This review focuses on the clinical illness of dengue infection in international travelers and provides a summary of the risk of infection for travelers, clinical features of infection, and an overview of dengue vaccines and their potential applicability to travelers. Four prospective studies of travelers to dengue-endemic destinations have shown that the dengue infection incidence ranges from 10.2 to 30 per 1,000 person-months. This varies according to travel destination and duration and season of travel. Dengue is also a common cause of fever in returned travelers, accounting for up to 16% of all febrile illnesses in returned travelers. Although the majority of infections are asymptomatic, a small proportion of travelers develop dengue hemorrhagic fever. The diagnosis of dengue in travelers requires a combination of serological testing for IgG and IgM together with either nucleic acid or NS1 antigen testing. Several vaccine candidates have now entered into clinical trials including ChimeriVax Dengue, which is currently in phase 3 trials, live-attenuated chimeric vaccines (DENV-DENV Chimera, Inviragen), live-attenuated viral vaccines, recombinant protein subunit vaccines, and DNA vaccines. Dengue infection in international travelers is not infrequent and may be associated with substantial morbidity. Furthermore, an accurate diagnosis of dengue in travelers requires the use of a combination of diagnostic tests. Although a vaccine is not yet available a number of promising candidates are under clinical evaluation. For now travelers should be provided with accurate advice regarding preventive measures when visiting dengue-endemic areas.

Clinical characteristics and outcome associated with pandemic (2009) H1N1 influenza infection in patients with hematologic malignancies: a retrospective cohort study

Pandemic H1N1 (pH1N1) influenza has been associated with a worldwide outbreak of febrile respiratory illness. Although impaired immunity, such as that caused by hematologic malignancy, has been identified as a risk factor for severe infection with this virus, the course of this infection has not been adequately characterized in patients with underlying hematologic malignancy in comparison with immune competent controls. We report our experience with severe pH1N1 infection in patients with hematologic cancers and compare this group to non-immunosuppressed patients. Data were retrospectively collected on all patients admitted to our institution with confirmed pH1N1 infection. Clinical characteristics, treatments and outcomes were compared between patients with hematologic malignancies and non-immunocompromised controls. Fifteen patients with hematologic malignancy and 49 controls were identified. The control group had higher baseline rates of asthma (p = 0.01) and smoking (p = 0.05) at baseline. Clinical features of infection in the two groups were similar, except for a higher prevalence of abnormalities on chest imaging in the group with malignancy (p = 0.05). No statistically significant difference in mortality was observed between the groups. Mean duration of hospitalization (22.1 days vs. 9.2 days, p = 0.04) and duration of antiviral treatment (9.9 days vs. 6.7 days, p < 0.05) were greater in the hematologic malignancy group. Hospitalized patients with hematologic malignancies with pH1N1 infection had greater durations of hospitalization and treatment than non-immunocompromised controls, possibly reflecting decreased clearance of the virus as a consequence of impaired immunity.

S12 Experience with Intrapleural Tissue Plasminogen Activator and DNase in the Treatment of Pleural Infection

IntroductionIntrapleural infection remains a significant cause of morbidity and mortality. In many patients medical management with chest tube drainage and antibiotics fails and surgical intervention is required. The MIST2 trial...

Clinical characteristics of infections caused by Roseomonas species and antimicrobial susceptibilities of the isolates

Human infections due to Roseomonas species are uncommon and the vast majority of reported infections are opportunistic and easy to treat. We retrospectively reviewed the computerized database of the Bacteriology Laboratory at the National Taiwan University Hospital to identify patients with infections caused by Roseomonas species during the period January 2000 to December 2010. Isolates of Roseomonas species were confirmed by 16S rRNA gene sequencing analysis. During the study period, 20 patients had cultures positive for Roseomonas species. R. mucosa was the most prevalent isolate (n = 18), followed by 1 each of R. gilardii and Roseomonas genomospecies 5. True infection caused by Roseomonas species was confirmed in 17 (85%) patients. Most (n = 12, 71%) of these infections were health care–associated infection. The majority of the patients (n = 12, 71%) had underlying diseases. Malignancy was the most common underlying disease, and catheter-related bloodstream infection was the most common type of infection. The antimicrobial susceptibility patterns varied among the different Roseomonas species. In conclusion, Roseomonas species can cause infection in children and adults regardless of immune status. Because different Roseomonas species may have different clinical features and susceptibility profiles, molecular studies are necessary to identify Roseomonas isolates to the species level.

Colonisation and infection due to Enterobacteriaceae producing plasmid-mediated AmpC β-lactamases

To investigate the epidemiology and clinical features of infections caused by Enterobacteria producing plasmid-mediated AmpC β-lactamases (pAmpC), which are emerging as a cause of resistance to extended-spectrum cephalosporins. A prospective multicentre cohort of patients with infection/colonisation due to pAmpC-producing Enterobacteriaceae was performed in 7 Spanish hospitals from February throughout July 2009. pAmpCs were characterised by PCR and sequencing. 140 patients were included; organisms isolated were Escherichia coli (n = 100), Proteus mirabilis (n = 20), Klebsiella pneumoniae (n = 17), and others (n = 3). Overall, 90% had a chronic underlying condition. The acquisition was nosocomial in 43%, healthcare-associated in 41% (14% of those were nursing home residents), and community in 16%. Only 5% of patients had no predisposing feature for infection with multidrug-resistant bacteria. Nineteen percent of patients were bacteraemic. Inappropriate empirical therapy was administered to 81% of bacteraemic patients, who had a crude mortality rate of 48%. The most frequent enzyme was CMY-2 (70%, predominantly in E. coli and P. mirabilis) followed by DHA-1 (19%, predominantly in K. pneumoniae). pAmpC-producing Enterobacteriaceae caused nosocomial, healthcare-associated and community infections mainly in predisposed patients. Invasive infections were associated with high mortality which might be partly related to inappropriate empirical therapy.

Cryptococcus gattii: The Tip of the Iceberg

TO THE EDITOR—Our historical understanding of Cryptococcus gattii depicts a fungus that is geographically restricted to tropical and subtropical regions, where it has a propensity to cause central nervous system (CNS) disease in persons with normal immune systems. This fungus, which only recently has been appreciated as a species distinct from its more well-known and cosmopolitan sibling, Cryptococcus neoformans, has been described as particularly prevalent in areas that contain eucalypts, especially in northern Australia, South America, and parts of Africa and Asia. Although C. gattii was recognized some time ago to cause disease in North America, particularly southern California, the infection did not become particularly concerning until its emergence on Vancouver Island, British Columbia, during the late 1990s. Subsequently, there were reports emphasizing its presence as a significant human and veterinary pathogen in the broader Pacific Northwest (PNW), especially in the US states of Washington and Oregon [1, 2]. Most recently, detailed analyses of the genetics of organisms isolated from multiple locations in the United States emphasize 2 important conclusions: emergence of a notable outbreak of genetically similar strains in the PNW and increasing recognition of other strains as a cause of disease across a larger area in the United States (Figure 1). The article in this issue by Harris et al summarizes efforts by the Centers for Disease Control and Prevention (CDC) to describe the unique clinical features of infection with outbreak and nonoutbreak C. gattii strains in the United States [3]. The authors are to be congratulated for herculean efforts performed in compiling recognized cases, efforts dependent on extensive communication and follow-up with referring clinicians in geographically dispersed regions. Despite limitations in methodology, some important clinical observations are introduced, with controversies raised. Methods used in this study separate recognized cases as those caused by outbreak and nonoutbreak C. gattii strains. Although the intent of this separation is well founded—to evaluate the clinical features of infections caused by the unique organism arising in the PNW—the logic justifying this separation seems to be somewhat convoluted and arbitrary, yielding, at best, interesting hypotheses from these data rather than firm conclusions. Investigators state that the case patients infected with outbreak strains were defined as having likely acquired infection from the PNW or British Columbia, contingent on exposure within 1 year of clinical presentation. Isolates were then considered to be outbreak strain if identified as one of the genotypes that have been described from the area (VGIIa, VGIIb, and VGIIc). Isolates in the CDC collection are largely separated by region of endemicity, with VGII isolates arising in the PNW and others (VGI and VGIII) arising in different regions. However, attention is drawn to the recognized case caused by a VGII strain that arose in a patient with only geographic exposure on Hawaii; this case was considered to be caused by a nonoutbreak strain because of the exposure. Perhaps this is justified, because of the unpublished findings, through use of multilocus sequence typing, that this VGII strain appears to be genetically dissimilar (E. Byrnes, unpublished communication, July 2011). However, the distribution of VGII in the United States may, in fact, be more broad; an isolate recovered from the environment in California in the 1990s was subsequently found to be VGIIa–very similar to the recently recovered VGIIa isolates from the PNW [2]. These issues outline a problem inherent in the definition used in this study: overlaps, including the presence of VGII genotypes in areas not in the PNW and the presence of VGI and VGIII isolates in the PNW [2, 4], make the separation between outbreak and nonoutbreak somewhat arbitrary. Received 26 August 2011; accepted 30 August 2011. Correspondence: Kieren A. Marr, MD, Division of Infectious Diseases, Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross 1064, Baltimore, MD 21205 (kmarr4@ jhmi.edu). Clinical Infectious Diseases The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. 1058-4838/2011/5312-0004$14.00 DOI: 10.1093/cid/cir738

Clinical characteristics of infections caused by Tsukamurella spp. and antimicrobial susceptibilities of the isolates

To investigate the clinical and microbiological characteristics of infections caused by Tsukamurella spp., the computerised database of the Bacteriology Laboratory at National Taiwan University Hospital (Taipei, Taiwan) was reviewed retrospectively to identify patients with infections caused by this species during the period January 1997 to December 2008. All of the isolates had been initially misidentified as Rhodococcus spp. Identification of Tsukamurella isolates to species level was carried out by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) analysis of the heat shock protein gene ( hsp65) as well as 16S rRNA gene sequencing. During the study period, a total of eight patients with Tsukamurella infection and two patients with Tsukamurella colonisation were identified. Tsukamurella tyrosinosolvens ( n = 6) was the most prevalent species, followed by Tsukamurella spumae ( n = 3) and Tsukamurella pulmonis ( n = 1). Keratitis was the most common type of infection ( n = 3), followed by catheter-related bloodstream infection ( n = 2). One of the patients with Tsukamurella infection died due to bacteraemia; the other seven patients with Tsukamurella infection had favourable outcomes. The three species had different drug susceptibility patterns; T. pulmonis was the most resistant pathogen, with higher minimum inhibitory concentrations of clindamycin (>2 mg/L), erythromycin (2 mg/L) and tetracycline (8 mg/L) than those for the other Tsukamurella spp. In conclusion, strains of Tsukamurella spp., including T. spumae, are uncommon causative agents of ocular infections and bacteraemia in cancer patients. Molecular diagnostic methods are essential to distinguish species in the Tsukamurella genus from species in other phylogenetically related genera such as Rhodococcus.