Journal of Infection - Articles in Press

A cluster of Plasmodium Vivax Malaria in an expedition group to Ethiopia: Prophylactic efficacy of ATOVAQUONE/PROGUANIL on liver stages of P.VIVAX - Accepted Manuscript

Alice Mavrogordato, Andrew M.L. Lever — 2012-05-18

Summary: Objectives: Complete prevention of malaria especially P. falciparum is the goal of prophylaxis. A survey, designed to ascertain reasons behind the choice of malaria prophylaxis, compliance and side effects, and to gather data on acquired malaria, identified a cluster of P. vivax infection in a cohort of 33 who travelled to Ethiopia on a scientific expedition.Methods: A questionnaire based survey of travellers who took part in a scientific survey and rafting expedition in Ethiopia between October and December 2005 on their return from the expedition and two years later.Results: 31 of 33 subjects completed the survey fully. Evidence was obtained on factors influencing choice of, and adherence to prophylaxis and the incidence and type of malaria related to prophylaxis. Over the two year follow up period 32% of travellers developed P. vivax malaria. Of those taking Mefloquine and Doxycycline 50% and 66% respectively developed malaria, compared to none taking Atovaquone/Proguanil as prophylaxis. Awareness and management of malaria was inadequate in several cases. Failure to use Primaquine led to second relapses.Conclusions: Within this cluster, prophylaxis against P. falciparum was successful. Widespread failure of prophylaxis against P.vivax malaria was documented despite the use of recommended regimes of known efficacy against the parasite. Atovaquone/Proguanil had the least side effects and afforded the highest protection. Atovaquone/Proguanil may provide previously unrecognised protection against liver stages of P. vivax.Summary: A survey of compliance, efficacy and side effects of malaria prophylaxis identified a cluster of infection in a cohort of 33 travellers to Ethiopia 32% of whom developed Plasmodium vivax malaria. Of those taking Mefloquine and Doxycycline as prophylaxis 50% and 66% respectively subsequently developed P. vivax, compared to none taking Atovaquone/Proguanil. Failure to use Primaquine led to second relapses. Although prophylaxis against Plasmodium falciparum was successful P.vivax malaria infection was common despite the use of recommended regimes of known efficacy against the parasite. Atovaquone/Proguanil may provide previously unrecognised protection against liver stages of P. vivax.

High Detection rate of Human papillomavirus in Anal brushings from Women attending a proctology clinic - Accepted Manuscript

2012-05-17

Summary: Objectives: To study human papillomavirus (HPV) anal infection in anal brushings from women attending a proctology clinic, and compare results with those obtained from paired cervical brushings.Methods: Women attending a university hospital proctology clinic for anal conditions or as part of a screening campaign, were enrolled consecutively, excluding those reporting previous HPV-related pathologies. HPV genotypes in anal and cervical brushings were determined by sequencing and, in most cases, type-specific viral loads were measured.Results: HPV DNA was detected in 28.3% of anal brushings, with 47.4% of HPV genotypes being high risk. Cervical HPV detection was at almost the same rate but HPV status was discordant in about half those women with at least one positive specimen. Abnormal cytological findings were more common in anal than in cervical samples, in particular in the proctology outpatients.Viral load measurements excluded the existence of a multiple infection with genotypes detected in discordant anal- and cervical-paired samples and showed a significant correlation between anal and cervical paired concordant samples.Conclusions: The high rate of HPV detection in anal brushings that is not usually related to HPV positivity in cervical brushings could provide support for offering HPV DNA tests to women attending proctology clinics.

A Re-Audit Of Outcomes In Patients With Esbl Producing Escherichia Coli Bacteraemia - Accepted Manuscript

Mark Melzer, Irene Petersen — 2012-05-14

Using the NIHR Comprehensive clinical Research Network for Infectious Diseases and Microbiology Research - Accepted Manuscript

Robert C. Read, Gail Thomson — 2012-05-14

Concurrent lung infections in patients with hematological malignancies and invasive pulmonary aspergillosis: How firm is the Aspergillus diagnosis? - Uncorrected Proof

Sarah P. Georgiadou, Dimitrios P. Kontoyiannis — 2012-05-11

Summary: Background: Immunocompromised patients with hematological malignancies and/or recipients of hematopoietic stem cell transplants are constantly exposed to several fungal, bacterial, and viral respiratory pathogens.Methods: We retrospectively evaluated all patients with invasive pulmonary aspergillosis (IPA) and underlying hematological malignancies for the presence of concurrent, microbiologically documented pulmonary infections during a 5-year period (2005–2010).Results: We found 126 such patients that frequently had coinfections (49%) with respiratory pathogens other than Aspergillus species, with a higher rate in patients with probable IPA (53%) than in those with proven IPA (29%; P=0.038).Conclusions: As the majority of patients with IPA in daily practice have probable IPA, often according to only the combination of positivity for serological biomarkers and radiological findings, our data may raise skepticism about both the certainty of IPA diagnosis and the evaluation of response to antifungals in a subset of these patients.

Additive benefits of pneumococcal and influenza vaccines among elderly persons aged 75 years or older in Taiwan – A representative population-based comparative study - Uncorrected Proof

Yu-Chia Chang, Yiing-Jenq Chou, Jen-Yin Liu, Te-Feng Yeh, Nicole Huang — 2012-05-07

Summary: Objective: It remains unclear whether pneumococcal vaccine provides additional protection to the elderly who have already vaccinated with influenza vaccine. This retrospective cohort study aimed to assess the additive effect of pneumococcal and influenza vaccines on the risk of mortality, hospitalization, and inpatient expenditure in the elderly aged 75 years or older in Taiwan.Methods: Data were extracted from the National Health Insurance claims data of a nationally representative elderly sample. To reduce potential selection bias, we employed a propensity score matching method to classify the vaccination status into 3 groups. Multivariable logistic and linear regression models were used to compare the outcomes among different groups.Results: Each group contained 8142 subjects. The results indicated that an additive effect of receiving both vaccines was associated with a significantly lower all-cause mortality (relative risk [RR]: 0.74; 95% confidence interval [CI]: 0.57–0.96), hospitalization of all diseases including pneumonia, influenza, chronic obstructive pulmonary disease, respiratory diseases, and congestive heart disease (RR: 0.77; 95% CI: 0.67–0.90), and a 13% reduction (95% CI: 0.81–0.94) in inpatient expenditures of all diseases when compared with receiving influenza vaccine alone.Conclusions: This study confirmed that vaccination of elderly individuals with pneumococcal vaccine and influenza vaccine concomitantly has substantial beneficial effects.

Pandemic (H1N1) 2009 virus infection: Prolonged viral shedding and the role of corticosteroids - Corrected Proof

Slinporn Prachayangprecha, Yong Poovorawan, Sawan Kanchana — 2012-05-04

We appreciate your comments and would like to thank you for your interest in our article on persistent pandemic H1N1 2009 viral shedding in patients with underlying diseases. The patient with SLE described in our paper did not has any active disease and had not received corticosteroids. Only one case with asthma and COPD had intermittently been treated with corticosteroids. None of them received corticosteroids during early treatment or for complications from pandemic H1N1 2009 infection. SLE is a chronic immunological defects disease affecting many organs which requires appropriate treatment with immunosuppressive drugs. Many studies have demonstrated that in immunocompromised patients for example, with SLE or malignancy, immunosuppressive therapy increases both severity and complications of influenza virus infection, irrespective of corticosteroids being or not being administered. Due to the disease itself, viral shedding is prolonged despite prompt treatment with antiviral drugs. Prolonged infection in immunocompromised patients can cause emergence of antiviral drug (Oseltamivir) resistance as shown in our previous study on a fourteen-year old with SLE who had been on high dose corticosteroid treatment and received the antiviral drug Oseltamivir upon infection with pandemic H1N1 2009. This patient developed severe symptoms including pneumonia, respiratory failure and died during hospitalization, with Oseltamivir resistance detected in this individual. There have been reports on the success of early corticosteroid treatment of severe life-threatening pneumonia caused by pandemic H1N1 2009 or, to prevent progression to acute respiratory distress syndrome (ARDS). On the other hand, a clinical study in Japan has found that patients receiving systemic corticosteroid treatment and early administration of antiviral agents for pneumonia with acute wheezing caused by pandemic H1N1 2009 did not experience significant improvement upon systemic steroid treatment. We agree with Rapos A. et al, that in case of severe infection with the influenza virus the use of systemic steroids may increase the severity of symptoms as a result of a weakened immune system, which can lead to persistent shedding. However, although treatment results of corticosteroids in severely affected patients with pandemic H1N1 2009 infection are controversial, additional evidence could be further obtained by performing a controlled clinical study aimed at clarifying the role of systemic steroid treatment.

Pandemic (H1N1) 2009 virus infection: Prolonged viral shedding and the role of corticosteroids - Corrected Proof

Alwyn Rapose — 2012-05-04

The article by Kanchana et al., in the October 2011 edition of the Journal of Infection presenting their findings of persistent shedding of the Pandemic H1N1 2009 virus in patients with underlying medical diseases makes very interesting reading. I agree with the authors' conclusion that patients with underlying diseases have a higher proportion of post-treatment positive PCR and recommendations for prolongation of therapy. On detailed review of the article, it appears that 11 of these 33 patients had chronic lung disease and 1 patient had SLE. I question whether these patients also received systemic steroids for these conditions during the time of infection with the Pandemic H1N1 2009 virus. Small studies showed lower mortality rates in patients with severe H1N1 infections using protocols which involved systemic steroid use. However, contrary to this, larger studies – large multi-center study (245 patients) in South Korea, and a French study (208 patients with ARDS)- have demonstrated a higher mortality associated with steroid use. At the peak of the pandemic we had treated a 52-year-old previously healthy male patient with severe H1N1 infection who developed respiratory failure requiring prolonged intubation. This patient experienced persistent fevers and virus shedding in-spite of early initiation of therapy with oseltamivir. PCR for the H1N1 virus returned negative by day 21. He received oseltamivir throughout this period and there was no resistance detected. Unfortunately, he developed ARDS and was treated with systemic steroids, and developed Cryptococcus meningitis. I suggest that use of systemic steroids in patients with severe H1N1 infection contributes to compromise of the immune status and hence prolonged infection and persistent virus shedding. In addition it leaves the patient at increased risk for opportunistic infections like invasive fungal disease. It appears that the cumulative experience from the pandemic of the H1N1 virus infection should result in recommendations against the use of systemic steroids for treatment of respiratory failure in these patients.

Bacterial co-infection with H1N1 infection in patients admitted with community acquired pneumonia - Corrected Proof

2012-04-30

Summary: Background: Bacterial co-infection is an important contributor to morbidity and mortality during influenza pandemics .We investigated the incidence, risk factors and outcome of patients with influenza A H1N1 pneumonia and bacterial co-infection.Methods: Prospective observational study of consecutive hospitalized patients with influenza A H1N1 virus and community-acquired pneumonia (CAP). We compared cases with and without bacterial co-infection.Results: The incidence of influenza A H1N1 infection in CAP during the pandemic period was 19% (n, 667). We studied 128 patients; 42(33%) had bacterial co-infection. The most frequently isolated bacterial pathogens were Streptococcus pneumoniae (26, 62%) and Pseudomonas aeruginosa (6, 14%). Predictors for bacterial co-infection were chronic obstructive pulmonary disease (COPD) and increase of platelets count. The hospital mortality was 9%. Factors associated with mortality were age ≥65 years, presence of septic shock and the need for mechanical ventilation. Although patients with bacterial co-infection presented with higher Pneumonia Severity Index risk class, hospital mortality was similar to patients without bacterial co-infection (7% vs. 11%, respectively, p = 0.54).Conclusion: Bacterial co-infection was frequent in influenza A H1N1 pneumonia, with COPD and increased platelet count as the main predictors. Although associated with higher severe scales at admission, bacterial co-infection did not influence mortality of these patients.

Etiology of acute diarrhea due to enteropathogenic bacteria in Beijing, China - Corrected Proof

2012-04-30

Summary: Objectives: Acute diarrhea is of great concern due to considerable morbidity and mortality worldwide. The causative bacteria leading to acute diarrhea in general population remains unclear in China. This study was conducted to determine the etiology of acute diarrhea using a sentinel hospital-based surveillance network in Beijing.Methods: Active surveillance was implemented from April 2010 to December 2011 on two random days per week by enrolling every tenth diarrheal patients admitted to seventeen intestinal clinics. Shigella spp., Vibrio spp, Salmonella spp., diarrheagenic Escherichia coli and other genera of bacteria, were investigated from 4803 outpatients with acute diarrhea by microbiological methods.Results: The pathogenic bacteria recovered out from fecal samples of 968 (20.2%) patients had the following profile: Shigella spp. (5.9%) was the most prevalent pathogen, Vibrio parahaemolyticus (5.2%), Salmonella spp. (3.9%) and enteropathogenic E. coli (EPEC) (0.9%) had from the second to fourth highest prevalence, respectively. Of the 55 co-infections detected, V. parahaemolyticus was the most common pathogen from 28 cases (50.9%), with the main combination of V. parahaemolyticus and Samonella. The highest proportion of all causative bacteria was found in adults aged 20–39 year and in summer as well as early autumn. The clinical symptoms associated with specific bacterial infection, such as fever, abdominal pain, tenesmus, nausea, vomiting, and watery and bloody stool, were observed frequently in diarrheal patients.Conclusion: Shigella spp., V. parahaemolyticus, Salmonella spp., and EPEC are important enteropathogenic bacteria causing acute diarrhea in Beijing. To execute reasonable interventions, the comprehensive and continuous surveillance is needed to identify the prevalence of different enteropathogeic bacteria.

Epidemiology and clinical characteristics of parainfluenza virus 3 outbreak in a Haemato-oncology unit - Uncorrected Proof

2012-04-30

Summary: Objectives: We describe molecular investigations of a large hospital outbreak of parainfluenza virus type 3 (PIV3), in which 32 patients became infected. We outline infection control measures that successfully limited further spread of PIV3 in a Haemato-oncology unit.Methods: Clinical retrospective review of infected haemato-oncology patients was undertaken. PIV3 haemagglutinin sequences from each case (n = 32) and local epidemiologically unlinked controls (n = 53) were compared to identify potential linkage.Results: PIV3-infected patients presented with upper (n = 18) and lower (n = 11) respiratory tract infections, 3 showed pyrexia only and one was asymptomatic. All symptomatic patients received antibiotics; bacterial co-infection was confirmed in eleven patients. PIV3 infections were associated with lower mortality than documented previously; three of the PIV3-infected patients died (3/32; 9%). All deaths were associated with relapsed malignancies, and PIV3 was not believed to be the primary cause of death in any of these patients. Sequences from 27 cases clustered closely together, consistent with nosocomial infections from PIV3 circulating within the ward. Factors favouring transmission were high patient turnaround between the day treatment unit and in-patient ward, and limited isolation facilities for immunocompromised and infected patients, especially within the day treatment unit. New infections reduced to baseline levels three days after enhanced infection control interventions were introduced.Conclusions: Molecular epidemiological analysis provided evidence for nosocomial transmission of PIV3 infection that facilitated effective implementation of infection control measures. These were instrumental in restricting further spread of the virus among high-risk patients.

Quadrivalent meningococcal conjugated vaccine: A routine or selective vaccine in Europe? - Corrected Proof

Cristina Masuet-Aumatell, Ray Borrow, Jane N. Zuckerman — 2012-04-27

At present, two quadrivalent A, C, Y, W135 meningococcal conjugate vaccines are licensed, one in Europe and two in the United States of America and Canada, both of which can be administered from 2 to 55 years of age, or even since 9 months of age in children at increased risk for invasive meningococcal disease, and can be used interchangeably because of their similar efficacy and safety profiles. This editorial reviews the public health approach to the elimination of meningococcal disease which varies from country to country by applying either a strategy of national routine or selective immunisation.

Chronic Q fever: Expert opinion versus literature analysis and consensus - Corrected Proof

Didier Raoult — 2012-04-25

Summary: Q fever has long been considered a rare disease. The extensive outbreak in the Netherlands generated a body of literature based solely on the consensus in the Netherlands. As a long-standing expert on Q fever, I offer my experience and recommendations to the E-CDC and the Dutch Q fever Consensus Group. My (biased) opinion is that experts deeply involved in the field continue to be useful in the management of outbreaks and can avoid decisions that produce an unfavorable progression in patients. Here, I propose that the definition of “chronic Q fever” be avoided and suggest a new score-based diagnosis for Q fever endocarditis and vascular infection.

Rapid diagnosis of influenza: An evaluation of two commercially available RT-PCR assays - Corrected Proof

2012-04-19

Summary: Objective: To evaluate the sensitivity and specificity of influenza virus detection by two commercial reverse transcriptase PCR methods compared with a reference real-time PCR.Methods: 122 clinical specimens were tested on Xpert® Flu and RealStar® Influenza Screen & Type. A reference real-time RT-PCR, at a specialist laboratory was chosen as the gold standard for comparison.Results: RealStar® Influenza Screen & Type had higher sensitivity for influenza A and influenza B respectively (92.3% and 88.2%) when compared to Xpert® Flu (78.8% and 76.5%). Both tests had excellent specificity.Conclusions: The simplicity and speed of the Xpert® Flu system could allow it to be used in the near-patient setting; however in circumstances where excluding a diagnosis of influenza may be critical, negative specimens may need to be repeated using a more sensitive assay.

The impact of A(H1N1)pdm09 infection on renal transplant recipients: A multicenter cohort study - Corrected Proof

2012-04-19

Organ transplant recipients constitute a major risk group for the current pandemic because they receive long-term immunosuppressive drugs that alter immune mechanisms. In this context, we read with interest the recent paper by Redelman-Sidi et al. who described mild clinical courses of A(H1N1)pdm09 in cancer patients and hematopoietic stem cell transplant recipients. Currently, there are still limited data available on clinical course, complications, and outcome of the A(H1N1)pdm09 in renal transplant recipients (RTRs). We present here a large multicenter cohort study to characterize the clinical features of A(H1N1)pdm09, identify the risk factors for allograft failure and death attributable to A(H1N1)pdm09 infection, and evaluate the long-term allograft functions after A(H1N1)pdm09 infection.

Long-term chikungunya infection clinical manifestations after an outbreak in Italy: A prognostic cohort study - Corrected Proof

2012-04-19

Summary: Objectives: Following a Chikungunya (CHIKV) outbreak in Italy, a cohort study was conducted to describe the infection long-term clinical course and outcome.Methods: Persons identified through active and passive surveillance as confirmed or possible CHIKV cases during the outbreak were enrolled and interviewed by trained public health nurses, between 4–5 and 12–13 months following the acute stage. Patients reporting persistent clinical symptoms were evaluated by rheumatologists. Serum samples were obtained and anti-CHIKV specific IgG and IgM immune responses detected. Only confirmed cases who completed the follow-up were analysed.Results: Out of 250 patients, 66.5% still reported myalgia, asthenia or arthralgia (most frequent sign) after 12 months. Functional ability, measured by the ROAD index, was more impaired for lower extremities (3.75; Inter Quartile Range – IQR 4.4), and the activities of daily living (average 4.2; IQR 5). Variables independently associated with the presence of joint pain at 12–13 months were increasing age, and history of rheumatologic diseases). Elderly, females, and persons with history of rheumatologic diseases had higher anti-CHIKV IgG titres at 12–13 months.Conclusions: This study confirms, in an unselected population, that the long-lasting burden of CHIKV infection is significant.

Factors associated with cerebrospinal fluid HIV RNA in HIV infected subjects undergoing lumbar puncture examination in a clinical setting - Corrected Proof

2012-04-19

Summary: Background: Cerebrospinal fluid (CSF) HIV RNA load may be associated with central nervous system (CNS) disease in HIV infected subjects. We investigated parameters associated with CSF HIV RNA within a large clinical cohort.Methods: All HIV infected subjects undergoing CSF examination including assessment of CSF HIV RNA at St. Mary's Hospital, London, UK between January 2008 and October 2010 were included. Parameters associated with a detectable CSF HIV RNA load were assessed using linear regression modelling. CSF viral escape was defined as CSF RNA >0.5 log10 copies/mL greater than plasma HIV RNA and >200 copies/mL where plasma HIV RNA <50 copies/mL.Results: Of 142 subjects, 99 were receiving antiretroviral therapy (ART). Plasma HIV RNA was <50 copies/mL in 69 subjects. CSF examination was performed for investigation of presumed HIV encephalopathy (IxHE, n = 57), other CNS diseases considered HIV related (n = 39), syphilis (n = 20) and CNS presentations not considered HIV related (n = 26). CSF viral escape was present in 30/142 (21%) subjects overall and in 9/69 (13%) of those on ART with undetectable plasma HIV RNA. Overall, plasma HIV RNA load was significantly associated with detectable CSF HIV RNA (p ≤ 0.001). In subjects with plasma HIV RNA <50 copies/mL, only CNS penetration effectiveness (CPE, 2008) score of <2 was significantly associated with detectable CSF HIV RNA (p = 0.044). In patients undergoing LP for IxHE both plasma HIV RNA and CPE scores were independently associated with detectable CSF HIV RNA (p = 0.019 & 0.003 respectively) which was not observed in subjects undergoing CSF examination for other medical reasons.Conclusions: In a clinical setting, CSF viral escape is observed frequently in 21% of subjects and is associated with different parameters depending on the clinical scenario.

Staphylococcus aureus infections in pediatric patients with diabetes mellitus - Corrected Proof

2012-04-09

Summary: Objectives: To describe Staphylococcus aureus infections in children with diabetes mellitus (DM).Methods: Children with DM (cases) and S. aureus infections (2/02-6/10) were identified from a surveillance database. Patient charts were reviewed, and S. aureus isolates were characterized by molecular methods. Cases were compared to age-matched controls without DM but with CA-S. aureus skin and soft tissue infections (SSTI) using conditional logistic regression.Results: Forty-seven cases were identified; 41 were matched with 123 controls. Four cases had osteomyelitis and 43 had SSTI. Mean age was 14.2 years and 63% of cases had hemoglobin (Hb) A1c levels above 10%. Cases and controls differed by gender (85% vs. 45% female, P < 0.001), BMI% (median 87% vs. 72%, P = 0.04), methicillin-resistant S. aureus (MRSA) infection (49% vs. 68%, P = 0.04), and recurrent infections (22% vs. 4%, P = 0.001). Among cases, 88% of recurrences were caused by MRSA.Conclusions: The majority of cases had poor glycemic control, more recurrences, fewer primary MRSA infections and were more likely to be female compared to a control group. Improved glycemic control may reduce the risk for infection, and decrease hospitalizations due to S. aureus infections.

Multidrug resistant bacteria in wounds of combatants of the Libyan uprising - Corrected Proof

2012-04-09

On the 17th of February 2011 an uprising started in Libya against the Kaddafi dictatorial regime and on the 23rd of October Libya was declared free of such regime. Although the uprising started peacefully, it evolved quickly into a military conflict that left thousands of Libyans dead and thousands more injured. The aim of the present work was to determine the identity and antimicrobial resistance profiles of the bacteria associated with wound infections in posttrauma patients who sustained their injuries during the uprising.

Encephalitis due to emerging viruses: CNS innate immunity and potential therapeutic targets - Corrected Proof

M. Denizot, J.W. Neal, P. Gasque — 2012-04-06

Summary: The emerging viruses represent a group of pathogens that are intimately connected to a diverse range of animal vectors. The recent escalation of air travel climate change and urbanization has meant humans will have increased risk of contacting these pathogens resulting in serious CNS infections. Many RNA viruses enter the CNS by evading the BBB due to axonal transport from the periphery. The systemic adaptive and CNS innate immune systems express pattern recognition receptors PRR (TLRs, RiG-1 and MDA-5) that detect viral nucleic acids and initiate host antiviral response. However, several emerging viruses (West Nile Fever, Influenza A, Enterovirus 71 Ebola) are recognized and internalized by host cell receptors (TLR, MMR, DC-SIGN, CD162 and Scavenger receptor B) and escape immuno surveillance by the host systemic and innate immune systems. Many RNA viruses express viral proteins WNF (E protein), Influenza A (NS1), EV71 (protein 3C), Rabies (Glycoprotein), Ebola proteins (VP24 and VP 35) that inhibit the host cell anti-virus Interferon type I response promoting virus replication and encephalitis. The therapeutic use of RNA interference methodologies to silence gene expression of viral peptides and treat emerging virus infection of the CNS is discussed.

Opportunistic infections in patients with pulmonary alveolar proteinosis - Corrected Proof

2012-04-06

A case of pulmonary alveolar proteinosis (PAP) and Nocardia spp. brain abscess is described. A comprehensive review of the English-language literature was conducted to identify all reported cases of PAP and opportunistic infections between 1950 and July, 2010. This review describes the demographics, clinical manifestations, management, and outcomes of patients with PAP and opportunistic infections due to Nocardia spp., mycobacteria, or fungal pathogens.Summary: Objectives: To describe the demographics, clinical manifestations, treatment, and outcomes of patients with pulmonary alveolar proteinosis (PAP) who developed an opportunistic infection with Nocardia spp., mycobacteria or fungal pathogens.Methods: A case of PAP and Nocardia spp. brain abscess is described. A comprehensive review of the English-language literature was conducted to identify all reported cases of PAP and opportunistic infections between 1950 and July, 2010.Results: Seventy five cases were reviewed. Thirty two patients (43%) had nocardial infection, 28 (37%) mycobacterial infection, and 15 (20%) fungal infection. Thirty nine patients (65%) were male. Seventeen patients (23%) were immunosuppressed. Twenty patients (27%) were active smokers. PAP was the initial diagnosis in 19 patients (33%), while infection presented first in 23 patients (40%); 16 patients (27%) had a concurrent diagnosis of PAP and infection. The average interval between PAP diagnosis and an opportunistic infection was 16 months. Lungs were the most common site of infection; extra-pulmonary infection was present in 27 patients (32%). Thirty nine patients (57%) survived through the follow-up period, while 31 died.Conclusions: Opportunistic infections can either precede or follow a diagnosis of PAP. PAP should be considered in apparently immunocompetent patients who present with an opportunistic infection and diffuse alveolar infiltrates.

Coxsackievirus B5, associated with neurological hand, foot and mouth disease, China - Corrected Proof

Y.F. Hu, Fan Yang, J. Du, T. Zhang, Y. Xue, Qi Jin — 2012-04-06

HFMD has emerged as a significant public health issue in China these years. In 2009, up to 1,155,525 cases in Mainland China, including 353 deaths, were confirmed by the Chinese Center for Disease Control and Prevention (China CDC) (http://www. moh.gov.cn/publicfiles/business/htmlfiles/mohbgt/s10639/201002/46043.htm). Numerous large epidemics of HFMD have occurred nationwide. The varying prevalence of neurologic manifestations of HFMD outbreaks is assumed to have been driven by distinct EV71 genotypes and co-infection with other viruses. Here, we report firstly a new distinct coxsackievirus B5 lineage involved in an outbreak of EV71-associated neurologic HFMD in Linyi City, Shandong Province, China.

IP-10 is an additional marker for tuberculosis (TB) detection in HIV-infected persons in a low-TB endemic country - Corrected Proof

2012-04-05

Summary: Objective: In Indian HIV-infected patients, IP-10 response to QuantiFERON-TB Gold In tube (QFT-IT) antigens has been associated to tuberculosis (TB). However, specificity for active TB was lower than that reported by QFT-IT, making accuracy for TB detection questionable. To investigate this uncertainty, likely due to India being highly endemic for TB, and to better identify TB correlates, we evaluated the IP-10-based assay in HIV-infected subjects in Italy, a low-TB endemic country.Methods: 195 individuals were prospectively enrolled; 118 were HIV-infected (21 with active TB, 97 without active TB, and distinguished as high/low-TB-risk). QFT-IT was performed and IP-10 was evaluated by ELISA.Results: Among the HIV-infected individuals, sensitivity for active TB was 66.7% by IP-10-based test and 52.4% (p = 1) by QFT-IT. IP-10-based assay showed a lower dependence on mitogen-response and CD4 counts than QFT-IT. Among subjects without active TB, a higher proportion of IP-10 responders was shown in high-TB-risk subjects than low-TB-risk subjects (40.0% vs 12.9%), similar to QFT-IT (37.1% vs 4.8%). Low-TB risk subjects showed 87.1% specificity for active TB by IP-10-based test vs 95.2% by QFT-IT.Conclusions: In a low-TB endemic country, besides IFN-γ, IP-10 response to QFT-IT is associated with active TB and TB risk factors in HIV-infected patients with lower dependence on mitogen-response and CD4 counts.

Use of the T-SPOT.TB assay to screen latent tuberculosis infection among the TB contacts in Shanghai, China - Corrected Proof

Yi Hu, Qi Zhao, Edward A. Graviss, Weili Jiang, Zhengan Yuan, Biao Xu — 2012-04-05

Summary: Background: There is limited information on the prevalence of latent tuberculosis infection (LTBI) and the risk factors among contacts of pulmonary TB, which might contribute significantly to TB burden and therefore become the major concern for TB control in Shanghai, China.Methods: A total of 45 diagnosed TB patients from each of 7 Shanghai districts were chosen and approximately 3 contacts per case were randomly selected. A structured questionnaire was used to acquire socio-demographic information and to assess the degree of exposure to index cases. LTBI screening was performed by T-SPOT.TB assay.Results: Of 969 enrolled contacts, 39% were men, average age was 45 ± 19.1 years, and 76.3% were household contacts. LTBI was identified in 29.6% of subjects. Those contacting smear-positive TB patients were 2.24 times (95%CI, 1.586–3.162) more likely to develop LTBI than those otherwise; household contact significantly increased the likelihood of LTBI by 1.52 times (95%CI, 1.061–2.180). Furthermore, among household contacts, the risk of LTBI was higher in spouses and first-degree relatives and increased with age and contact duration.Conclusions: A high prevalence of LTBI was observed among the TB contacts in Shanghai, highlighting the need of intervention among the household contacts and those contacting smear-positive TB patients.

Efficacy of semiquantitatively measured serum procalcitonin as a guide to cessation of antibiotic therapy in septic patients - Corrected Proof

2012-03-30

We read with interest the paper by Limper et al. We also believe that measurement of quantitative procalcitonin (PCT) was very useful for management of patients with bacterial infections. However, there are many hospitals that are unable to monitor PCT levels via quantitative methods around the world. Therefore, we reported the efficacy of semiquantitative PCT measurement.

Potential exposure of medical students to blood borne viruses on medical elective and the use of HIV post exposure prophylaxis - Corrected Proof

Jeremy Hunter, Tom Sulkin — 2012-03-26

Many medical students undertake their medical elective in countries with a high prevalence of blood borne viruses (BBVs). Despite awareness of under reporting of incidents with a high risk for exposure to BBVs in the literature and comprehensive pre-elective preparation no such incidents have ever been reported to the University Occupational Health Department at our institution (personal communication). To explore this further we have conducted an anonymous online questionnaire survey of the 2010 cohort of medical students at the Peninsula Medical School (PMS) on return from their elective.

Risk factors for clinical failure in patients hospitalized with cellulitis and cutaneous abscess - Corrected Proof

Jenana Halilovic, Brett H. Heintz, Jennifer Brown — 2012-03-22

Summary: Objective: The objective of this study was to evaluate clinical outcomes and risk factors associated with clinical failure in patients hospitalized with cellulitis with or without abscess.Methods: We performed a retrospective cohort study among adults admitted for cellulitis/cutaneous abscess from July 1, 2009 through June 30, 2010. Binary univariate and multivariate logistic regression analyses were performed to identify risk factors for clinical failure among evaluable patients.Results: A total of 210 cases met inclusion criteria. Among 106 evaluable cases, clinical failure occurred in 34 (32.1%) patients. Weight over 100 kg (Odds ratio [OR] = 5.20, P = 0.01), body mass index (BMI) ≥40 (OR 4.10, P = 0.02), inadequate empiric antibiotic therapy (OR = 9.25, P < 0.01), recent antimicrobial therapy (OR = 2.98, P = 0.03), and lower end of antibiotic dosing per treatment guidelines upon discharge (OR = 3.64, P < 0.01) were independent risk factors for clinical failure. Further subgroup analysis demonstrated that morbidly obese patients were at higher risk for clinical failure if they were discharged on a low oral dose of clindamycin or trimethoprim/sulfamethoxazole (P = 0.002).Conclusion: Inappropriate antimicrobial selection and dosing may adversely affect clinical outcomes among patients with cellulitis/cutaneous abscess. Obese individuals may be at particular risk for clinical failure secondary to inadequate dosing of antimicrobial therapy.

The risk of infections in HIV-HCV coinfected patients during antiviral therapy with pegIFN+RBV - Corrected Proof

2012-03-14

Summary: Objectives: Antiviral treatment with pegIFN/RBV decreases ANC and CD4+ cell count. An association between neutropenia, a low CD4+ cell count and infections has not been demonstrated so far in HIV-HCV coinfected patients.Methods: The incidence, type, and severity of infections were recorded in 85 HIV-HCV coinfected and 164 monoinfected patients receiving pegIFN/RBV for 48 weeks. ANC and CD4+ cell count were assessed every 4 weeks during therapy.Results: The incidence of infections was significantly higher in HIV-HCV than HCV-Mono (38% vs. 15%; p = 0.001). Types of infections: pneumonia (n = 16/n = 24), bacteraemia/sepsis (n = 5/n = 2), skin infections (n = 15/n = 12), urinary tract infections (n = 4/n = 1), OIs (n = 10/n = 1). The incidence of neutropenia grade 1, 2 3 or 4 was similar in HIV-HCV and HCV-Mono, respectively. The incidence of infections was not associated with neutropenia (HCV-Mono: p = 0.584; HIV-HCV: p = 0.23) or with CD4+ cell counts <200/μL (HIV-HCV: p = 0.29). OIs occurred more often in HIV-HCV patients with CD4+ cell count <200/μL (p = 0.024).Conclusions: Up to 38% and 15% of HIV-HCV coinfected and HCV-monoinfected patients develop infections during pegIFN+RBV therapy but without any correlation to neutropenia. Antibacterial prophylaxis/treatment should be considered early in HIV-HCV coinfected patients developing CD4+ cell counts <200/μL during antiviral therapy as these patients have an increased risk of OIs.

Clinical significance and outcome of polymicrobial Staphylococcus aureus bacteremia - Corrected Proof

2012-03-14

Summary: Objectives: The clinical significance of polymicrobial Staphylococcus aureus bacteremia (SAB) remains unclear. We therefore compared the clinical features and outcomes of polymicrobial and monomicrobial SAB.Methods: A prospective cohort study of patients with SAB was performed during a 20-months. Polymicrobial SAB was defined as the simultaneous isolation of S. aureus and other microorganisms from blood cultures. However, Corynebacterium spp., Bacillus spp., and coagulase-negative staphylococci were considered contaminants unless they were related to device infection and grew in two or more blood cultures.Results: During the study period, 44 (10%) patients had polymicrobial and 412 (90%) had monomicrobial SAB. A total of 54 microorganisms were isolated from the former, with Enterococcus spp. (22%) being the most common. Independent risk factors for polymicrobial SAB included neutropenia (odds ratio [OR] 3.5, p = 0.02), biliary tract catheters (OR 5.0, p = 0.001), and intra-abdominal infection (OR 10.3, p < 0.001). Clinical outcomes were significantly worse among patients with polymicrobial than monomicrobial SAB, including bacteremia-related and 7-day mortality rates. Independent predictors of bacteremia-related mortality were solid tumors (HR 2.0, p = 0.03) and polymicrobial SAB (HR 2.8, p = 0.007).Conclusions: Polymicrobial SAB is associated with more severe illness than monomicrobial SAB, with neutropenia, biliary tract catheters and intra-abdominal infection being significant risk factors for polymicrobial SAB.

Lack of oseltamivir-resistance in A/H1N1p-infected patients, Singapore - Corrected Proof

2012-03-14

There have been increasing reports of oseltamivir-resistance in patients infected with influenza A/H1N1p in the literature especially amongst immunocompromised patients. However, such studies may be unduly highlighted due to their positive findings in this regard. Other studies from this Southeast Asian-Pacific region, including a recent article in your Journal, reported a lack of oseltamivir-resistance in patients infected with influenza A/H1N1p. Here in Singapore, apart from three pediatric immunocompromised cases that have been reported elsewhere (all identified between August 2009 to June 2010), and despite a one-year period of surveillance (from July 2009 to August 2010), we have found no further cases of oseltamivir-resistance in any of our other influenza A/H1N1p-infected, oseltamivir-treated patients, even in those on prolonged therapy. We would like to further characterize these other oseltamivir-treated cases to add to the literature on this rapidly changing situation. This study received approval from the Institutional Review Board of the National Healthcare Group (DSRB Ref: 2010/00665).

A population-based case-control analysis of the association between Herpes Zoster and Erectile Dysfunction - Corrected Proof

Yi-Hua Chen, Yi-Kuang Chen, Joseph J. Keller, Herng-Ching Lin — 2012-03-14

Summary: Purpose: To date, the occurrence of erectile dysfunction (ED) associating with herpes zoster (HZ) is only based on limited case reports. This case–control study aimed at examining the association between HZ and ED using a population-based dataset in Taiwan.Methods: A total of 6429 adults newly diagnosed with ED were identified as cases, and 38,574 subjects without any medical history of ED were extracted as controls. Conditional logistic regression models were performed.Results: In total, 1.03% out of the sampled subjects had been diagnosed with HZ within one year prior to the index date; a higher proportion of prior HZ was found among cases than controls (2.04% vs. 0.86%, p < 0.001). After adjusting for demographic characteristics, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, and alcohol abuse/alcohol dependence syndrome, conditional logistic regression suggested that cases were more likely to have previously been diagnosed with HZ than controls (OR = 2.24, 95% CI = 1.82–2.75). Furthermore, the odds of having been diagnosed with an HZ infection within one year prior to the index date were dramatically higher among patients with ED than controls among subjects aged 18–29 (OR = 6.07).Conclusions: We conclude that ED was associated with having been previously diagnosed with HZ, particularly among younger males.

Psychosocial determinants of 2009 pandemic influenza A (H1N1) vaccine acceptability among Indian health-care workers during the post-pandemic phase - Corrected Proof

2012-03-14

During the pandemic phase of influenza A H1N1, Maltezou et al., reported that only 21.8% of health-care workers (HCW) from Greece intended to get vaccinated against pandemic influenza A H1N1. Concerns about the vaccine safety, inadequate information and low self risk perception were the major reasons for vaccine denial among Greece HCW. It was suggested to implement mandatory vaccination policy for HCW to prevent nosocomial influenza A H1N1 infection and recently Maltezou et al., reported that physicians supported mandatory vaccination against vaccine-preventable diseases than others. World Health Organization (WHO) recommended influenza vaccination even during the post-pandemic period of influenza A H1N1. There is a paucity of research in reporting vaccine coverage and the determinants of intention to get vaccinated after pandemic influenza among common public including HCW worldwide. This surveillance is essential to respond to the future pandemic outbreaks. Our study explored for the first time the pandemic influenza A H1N1 vaccination coverage among the Indian HCW and their knowledge, perceptions and attitudes towards the vaccination. Since the emergence of pandemic 2009 H1N1, the total number of deaths of lab confirmed cases cumulative from May 2009 to December 2010 in India was 2, 728. Many efforts were taken by Indian Government in the management of pandemic 2009 influenza A H1N1. This study was carried out during July–October 2011 among HCW in Aarupadai Veedu Medical College and Hospital, Puducherry and Vinayaka Mission's Kirupananda Variyar Medical College & Hospital, Tamilnadu. Data was collected using self-administered questionnaire which consisted of multiple-choice and closed-ended questions. The study population was a convenience sample. The data retrieved was analyzed, percentage calculation was done for descriptive purposes, and univariate analyses were carried out using chi-square tests by using PRISM GraphPad, version 4.0; GraphPad Software Inc., San Diego, CA. We considered p < 0.05 as significant. The response rate to our questionnaire was 79% (957 out of 1214 approached). Study participants include 490 (51%) doctors, 232 (24.2%) nurses, 149 (15.5%) paramedical staffs and 86 (9%) other staffs (). A total of 314/957 (33%) reported to have received the vaccine from the working hospital and elsewhere. Among the 314 HCW who have received vaccination, 203/314 (65%) were men and remaining were female HCW. The highest coverage for influenza A H1N1 vaccination was among male HCW (P < 0.0001) (). It was observed that the representation of male HCW among vaccinees is higher than that of females, and female HCWs represent more in the group intending to get vaccinated (). A total of about 148/490 (30%) doctors, 58/232 (25%) nurses, 93/149 (62%) paramedical staffs and 15/86 (17%) other staffs reported to have received the influenza A H1N1 vaccination. Among the 314 HCW, who have received vaccination, 148/314 (47%) were doctors including staff and resident physicians, 58/314 (18.4%) were nurses, 93/314 (29%) were paramedical staffs and the remaining 15/314 (4.7%) belong to other staffs group. Representation of doctors among the HCW was higher in the vaccinated group. Majority of the study population perceived vaccine against H1N1 as effective (208/314, 66%, 202/346, 58% and 198/297, 67% respectively) and similar perception was observed for wearing face mask. Antiviral treatment was considered as effective by majority of the HCW in all the 3 different groups (). The reasons for denial of vaccine among non-vaccinated group and vaccine acceptance are shown in . The top concerns for denying vaccination were doubts about the efficacy of the vaccine, safety of the vaccine and fear for side effects (cited by 41%, 46% and 32% respectively). Among the vaccinated HCW, the majority of the doctors answered that they had vaccination as they fall under the risk group. The vaccine acceptance was associated with self-protection and being in the high risk group. Very few HCW believed that the vaccine is safe with no potential adverse effects. Our study describes in an HCW population from India, a poor coverage rate of influenza A H1N1 vaccination during the post-pandemic period and our results highlight the various factors associated with vaccination uptake. Low coverage rates among HCWs have been reported during the pandemic phase in many other countries during 2010. In this study, the vaccination coverage rates were low similar to that reported among HCW in the pandemic period. In our study, the positive correlation of male sex and vaccination uptake was very similar to many of the studies conducted during the pandemic phase. The reason for this gender difference is not clearly known and this is in contrast to the reported gender based differences in influenza A H1N1 vaccine uptake among university students. The majority of the vaccinated respondents were doctors and results are in agreement with several other studies conducted during the pandemic phase. Doubts about the vaccine efficacy, fear of adverse reactions were the main reasons cited by HCW for denying vaccination during the pandemic phase. Similarly, concerns about the safety, effectiveness of the vaccine and fear for side effects were top key elements for denial in our study group. For most of our study participants, self-protection, belief of being in the high risk group and concern about the risk of nosocomial transmission to patients were the important reasons for the acceptance of vaccination. This study is unique because it was conduced among the HCW during the post-pandemic phase. However, we realize that our study has limitations. This study cannot be generalized to the entire Indian HCW as it was conducted only in two teaching hospitals. Reporting bias always exist in self-reported survey. Self-administered questionnaires will yield fewer reports than the interviewer-administered questionnaires. It is possible that disinterested HCW towards vaccination and vaccinated HCW may not have participated in the survey. The choice of convenience sample is another limitation. However, the strength of the study is the representation of the large number of HCW, with wide range of opinions and concerns regarding the vaccination.

Biomarkers define the clinical response to dexamethasone in community-acquired pneumonia - Corrected Proof

2012-03-14

Summary: Objectives: Adjuvant dexamethasone treatment in patients with community-acquired pneumonia (CAP) can reduce length of hospital stay. Whether there are subgroups of patients that especially might benefit from corticosteroids is unknown. We hypothesized that a discrepancy between systemic inflammation and cortisol level can define a subgroup that lacks a sufficient cortisol response during CAP, and therefore particularly might benefit from corticosteroids.Methods: A secondary analysis was performed on data from hospitalized patients with CAP, randomized to a four-day course of dexamethasone (5 mg daily) or placebo. Subgroups were made based on plasma cytokine levels (interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1)) and total plasma cortisol on presentation. Intensive care unit (ICU) admission and mortality were assessed.Results: 275 Patients (131 dexamethasone, 144 placebo) were analyzed. In the subgroup of patients (n = 23) with a high cytokine response (IL-6 ≥ 92.5 pg/mL, IL-8 ≥ 14.8 pg/mL and MCP-1 ≥ 1154.5 pg/mL) and a discrepantly low cortisol (lowest 50%), dexamethasone treatment was associated with a significant decrease on a combined endpoint of mortality/ICU admission, as compared with placebo (0% vs. 43%, p < 0.01). In the subgroup of patients with a high cytokine response and high cortisol (n = 23), this favorable effect of dexamethasone was absent (30% vs. 39%, p: 0.67).Conclusions: In CAP patients presenting with a high pro-inflammatory cytokine response but a discrepantly low cortisol, adjuvant dexamethasone treatment was associated with a significant decrease in mortality/ICU admission.

Immune response to hepatitis B vaccination in HIV-positive adults with isolated antibodies to HBV core antigen - Corrected Proof

2012-03-14

Summary: Objective: To investigate the merits of vaccination against hepatitis B virus (HBV) in HIV-positive individuals with isolated antibodies to hepatitis B core antigen (anti-HBc).Methods: HIV-positive patients with isolated anti-HBc and CD4 counts >200cells/mm3 received HBV vaccination. An antibody titre to hepatitis B surface antigen (anti-HBs titres) ≥10 IU/L one month post-vaccination was termed an anamnestic response; a titre <10 IU/L was termed a primary response. Patients with primary responses received a 3-dose vaccine course. Anti-HBs titres in all responders were measured 12 and 24 months post-vaccination.Results: 37 patients were studied: 19 (51%) were co-infected with hepatitis C; median CD4 count was 443cells/mm3. 8/37 patients (22%) elicited an anamnestic response. 29/37 patients (78%) elicited a primary response. After a 3-dose vaccine course, 15/25 primary responders (60%) achieved anti-HBs titres ≥10 IU/L. HIV acquisition through injecting drug use was the only independent predictor of an anamnestic response (OR 22.9, CI 1.71–306.74, P=0.018). Median anti-HBs titres for anamnestic and primary responders were 51 IU/L (13–127) and 157 IU/L (25–650) respectively. Of all responders, 12/23 (52%) retained anti-HBs titres ≥10 IU/L at 24 months. Anti-HBs duration was not significantly different between anamnestic and primary responders.Conclusions: 23/37 HIV-positive patients (62%) with isolated anti-HBc achieved anti-HBs titres ≥10 IU/L after 1–3 vaccine doses. However, duration of this immune response was short-lived (

Actinomyces meyeri infection: Case report and review of the literature - Corrected Proof

Tasaduq Fazili, Donald Blair, Scott Riddell, Deanna Kiska, Shehzadi Nagra — 2012-03-09

Summary: Actinomyces meyeri is an uncommon cause of actinomycosis. We present a patient with pneumonia and empyema due to A. meyeri. The patient underwent open thoracotomy with decortication and was discharged home on a twelve-month course of oral penicillin. Review of the English literature revealed thirty-two cases of infection due to A. meyeri. The majority of patients were male, and a significant number had poor dental hygiene and a history of alcoholism. More than other Actinomyces species, A. meyeri causes pulmonary infection and has a predilection for dissemination. Prognosis is favorable with prolonged penicillin therapy combined with surgical debridement, if needed.

Re: Molecular characterisation of Staphylococcus aureus carrying the Panton-Valentine leukocidin gene in northern Spain - Corrected Proof

2012-03-09

In this journal, Marimon et al. recently reported the molecular epidemiology of MRSA strains carrying the Panton-Valentine Leukocidin gene in northern Spain. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strains harbouring the Panton-Valentine leukocidin (PVL) gene have recently emerged worldwide. The CA-MRSA USA 300 strain is known to cause a large proportion of outpatient skin and soft tissue infections, and more recently, this strain has been noted as an increasingly frequent cause of healthcare-associated infections in the United States. The epidemiology of CA-MRSA strains differs between the United States and the Asia-Pacific region, with the USA 300 clone (ST8 PVL-positive) and the Ocean Pacific clone (ST30 PVL-positive) being predominant in their respective geographical areas. Currently, most prevailing CA-MRSA strains in Japan do not carry PVL genes. A recent epidemiological study of 16 Japanese hospitals identified few PVL-positive CA-MRSA cases. However, in 2009, a nosocomial outbreak of the PVL-positive USA 300 clone occurred in our hospital. In this context, we evaluated the molecular epidemiology of the MRSA USA 300 clone in a tertiary care university hospital in Kyoto, Japan.

Hospitalizations from pandemic influenza (pH1N1) infections among patients with asthma or COPD in Spain - Corrected Proof

2012-03-09

We have read with interest a recent article in this journal which reviews factors associated with severe illness in pandemic 2009 influenza a (H1N1) infection. It describes that chronic lung disease appears to be a common co-morbidity in severe cases of pH1N1/09 infection including those requiring ICU admission and those resulting in death. However, the available information on the clinical course and outcomes of pH1N1 infections in persons suffering respiratory illness, particularly asthma or COPD, is still scarce, with non-conclusive results. To clarify this relationship, we used hospitalization data collected by the Spanish National Hospital Discharge Database, namely “Conjunto Mínimo Básico de Datos” (CMBD) that compiles all public and private hospital data, thereby covering more than 95% of hospital discharges. The CMBD is managed by the Spanish Ministry of Health that sets standards for registration and also performs periodic audits (CMBD). We used the database for 2009 and we selected all admissions with diagnosis ICD-9-CM code 488.1 (pH1N1). Discharges were grouped, according to the presence or not of asthma and COPD separately. The outcome variables analyzed were in-hospital mortality (IHM), length of hospital stay (LOS), and costs.

The effect of underlying clinical conditions on the risk of developing invasive pneumococcal disease in England - Corrected Proof

2012-03-05

Summary: Objective: To inform national policy making on the use of the 13-valent pneumococcal vaccine among risk groups we estimated the increased risk of invasive pneumococcal disease (IPD) outcomes among clinical risk groups. Three years of post 7-valent pneumococcal conjugate vaccine (PCV7) data was included to investigate the herd protection effects.Methods: Over 22,000 IPD patients in England (March 2002–March 2009 – aged 2 and over) were linked to their hospitalisation records. The prevalence of risk factors in these patients was compared to the prevalence of risk factors in the general population.Results: There was an increased odds ratio (OR) for hospitalisation (OR 11.7 2–15 years; 7.6 16–64; 2.7 65+) and death (OR 2.4 2–15 years, 3.9 16–64, 1.2 65+) from IPD among risk group. The most important risk factors that predict IPD are chronic liver disease, immunosuppression, and chronic respiratory diseases. Herd protection effects due to introduction of the 7-valent vaccine were identical in both patient groups as shown by the similar decline in the proportion of IPD caused by PCV7 serotypes in risk and non-risk groups.Conclusions: There is a marked increased risk of IPD among those with certain clinical conditions, suggesting potential benefit from a targeted vaccination approach. However, the indirect protection from conjugate vaccination of children suggests PCV vaccination of high-risk groups may not provide substantial additional benefit once herd immunity takes effect.

Superiority of 18F-FDG PET compared to 111In-labelled leucocyte scintigraphy in the evaluation of fever of unknown origin - Corrected Proof

N. Seshadri, L.I. Sonoda, A.M. Lever, K. Balan — 2012-02-27

Summary: Aim: To compare the accuracy of positron emission tomography (PET) using 18F-FDG (Fluorodeoxyglucose) PET with 111In-labelled leucocytes scintigraphy (LS) in patients with fever of unknown origin (FUO).Methods: Twenty-three consecutive patients with FUO were prospectively studied using whole-body LS and PET. Performance of the two modalities for identifying a cause of FUO was evaluated. Final diagnosis was based on biopsy, microbiological tests, clinical and imaging follow-up.Results: Abnormal tracer uptake was seen in 3/23(13%) and 14/23(61%) patients on LS and PET respectively, suggesting a higher sensitivity (p < 0.01) for the latter. All LS positive cases were identified on PET and confirmed as infection. The causes of FUO in the other PET positive patients were: infection (n = 3), vasculitis (n = 3), non-infectious inflammatory conditions (n = 2) and cancer (n = 1). No specific diagnosis was reached in 2 patients. Of 13 patients without a definite diagnosis following PET and LS, 10 made a spontaneous recovery during the follow-up period and no definite cause for FUO was found on investigation. Still's disease, Polymyalgia rheumatica and Chronic fatigue syndrome/Myalgic encephalomyelitis were diagnosed in the remaining three patients during follow-up. The results thus showed an overall sensitivity of 86% for PET and 20% for LS (p < 0.01). The overall specificity for FDG PET was 78% as against 100% for LS. PET had a PPV of 86% and a NPV of 78% whereas LS had a PPV of 100% and a NPV of 40%.Conclusion: PET has a higher sensitivity than LS in identifying the aetiology of FUO. PET/PET-CT, where available, should be used as the non-invasive investigation of choice in the assessment of patients with FUO.

Emerging trends in candidemia: A higher incidence but a similar outcome - Corrected Proof

2012-02-27

Summary: The clinical presentation and outcome of candidemia has changed in recent years. We compared two 5-year periods (2000–2004 and 2005–2009) in a single institution. We recorded 419 candidemia episodes during the study period (124 in the first period and 295 in the second period). We observed a significant increase in the number of cases per 1000 admissions per year, from 0.57 in 2000 to 1.52 in 2009 (χ2 LT <0.001). Candida albicans was the most frequently isolated species (42.2%), followed by Candida parapsilosis (34.4%) and Candida glabrata (12.9%). In the second period, episodes were associated with higher comorbidity and were more commonly nosocomial, with a more frequent catheter-related source and an increased rate of C. glabrata infection. No significant differences were observed in susceptibility by species during the study period. According to multivariate analysis, the independent factors associated with higher mortality were shock, age >50 years, elevated comorbidity score (Charlson index >6), and source of candidemia other than catheter. In contrast to the increase in comorbid conditions observed in recent years, mortality remained similar during both periods (∼37% during the first month). This finding could be attributed to a significant increase in catheter-related candidemia and better outcome, as well as to a potential improvement in the management of antifungal therapy in recent years.

Multidrug-resistant bacteria colonization amongst patients newly admitted to a geriatric unit: A prospective cohort study - Corrected Proof

2012-02-16

Summary: Objectives: To determine prevalence, incidence and risk factors of colonization by extended-spectrum β-lactamase-producing Enterobacteriacae (ESBLE), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE) in aged subjects admitted to an acute geriatric unit at a teaching hospital.Methods: During 12 months, 337 patients were screened by nasal, oropharyngeal, groin, axillary and rectal swabs upon admission and at discharge.Results: The prevalence of ESBLE, MRSA and VRE carriage upon admission was 11.6%, 7.5% and 0.6%, respectively. The incidence density of ESBLE and MRSA carriage was respectively of 1.77 and 2.40 new cases for 1000 patient-days. No cases of VRE acquisition were found. Risk factors for ESBLE colonization on admission were: multiple contacts with the hospital within the previous year, chronic catheter use and a high level of dependency. For MRSA, risk factors were: chronic wounds, anti-acid use and a high level of dependency.Conclusion: This study shows a high prevalence of asymptomatic colonization of ESBL-producing Escherichia coli in patients admitted to an acute geriatric ward, as high as MRSA carriage. A low functional status is a common risk factor both for ESBLE and for MRSA colonization and it highlights the need to reinforce infection control measures.

Presentation, etiology and outcome of pneumonia in younger nursing home residents - Corrected Proof

2012-02-13

Summary: Objective: Nursing home-acquired pneumonia characteristically affects elderly patients with multiple comorbidities; it is associated with multidrug-resistant (MDR) pathogens and a high mortality. We studied the specific impact of age on the presentation, etiology and outcome of patients with NHAP.Methods: Data from the prospective multicenter CAPNETZ database were used for a comparison of the hospitalized younger nursing home residents with pneumonia to those aged ≥ 65 years as regards clinical presentation, comorbidity, severity at presentation, etiology, and outcome.Results: Amongst 618 patients with NHAP, 16% of patients (n = 100) were aged; 65 years. Comorbidity was present in most patients with NHAP but the pattern of comorbidity differed significantly. The rate of potential MDR pathogens was low among both age groups (together around 5%). According to the CRB-65 score, NHAP presentation was less severe in the younger patients. Short- and long-term mortality was twice as low in the younger patients with rates of 12.9% vs 26.6%, and 24.3% vs 43.8%, p = 0.014 and 0.002), respectively. In contrast, the usage of mechanical ventilation was more than two-fold higher (12% vs 5%) (p = 0.008) in younger patients. Antimicrobial treatment strategies did not account for different outcomes.Conclusions: A considerable proportion of patients with NHAP are: 65 years of age. They differ from older patients in terms of clinical presentation, frequency and type of comorbidity, as well as outcome. NHAP is a heterogeneous entity, with age and comorbidity as the main determinant of NHAP characteristics.

Incidence and predictors of acute kidney injury associated with intravenous polymyxin B therapy - Corrected Proof

2012-02-06

Summary: Background: Increases in multidrug-resistance among gram-negative organisms have necessitated the use of polymyxins. To date, the incidence of acute kidney injury (AKI) associated with polymyxin B has not been evaluated using RIFLE criteria.Methods: Adult patients who received polymyxin B were retrospectively evaluated to determine the incidence of AKI during polymyxin B therapy using RIFLE criteria. Predictors of AKI were identified by comparing characteristics of patients with and without AKI.Results: A total of 73 patients were included. The incidence of AKI was 60%. Ten (14%) patients discontinued therapy due to nephrotoxicity. Median duration of polymyxin B was 11 days with a median cumulative dose of 18 mg/kg. Concomitant nephrotoxins were received in 69 (95%). Patients with AKI had a higher median cumulative dose (1578 mg vs. 800 mg; p = 0.02), a higher body mass index (BMI) (27.2 vs. 24.5 kg/m2; p = 0.03), and were more likely to receive vancomycin (82% vs. 55%; p = 0.03) compared to those without AKI. After controlling for polymyxin B duration, independent predictors of AKI were higher BMI and concomitant vancomycin.Conclusions: The incidence of AKI during polymyxin B therapy was 60%. Further studies are needed to define dosing parameters that maximize efficacy and minimize nephrotoxicity.

Chronic Hepatitis E as a cause for cryptogenic cirrhosis in HIV - Corrected Proof

2011-12-07

Summary: Chronic Hepatitis E infection (HEV) is reported in immunocompromised patients. A 45-year-old HIV-infected man had no cause found for a persistent transaminitis which predated commencement of antiretroviral therapy. Hepatic elastography and liver biopsy revealed cirrhosis. In 2010, he tested positive for HEV IgM/IgG antibodies. Plasma HEV RNA was detected. Archived samples revealed HEV viraemia since 2000. A 24-week course of pegylated interferon was commenced and HEV RNA became undetectable at week 4 until week 27 post treatment cessation. Chronic HEV infection should be considered in HIV patients as a cause for unexplained transaminitis and cryptogenic liver cirrhosis.

First isolation of Tropheryma whipplei from bronchoalveolar fluid and clinical implications - Corrected Proof

2011-12-06

Summary: A patient presented diffuse pulmonary parenchymal micronodules. Tropheryma whipplei was detected in the saliva, a bronchial biopsy and bronchoalveolar fluid. PAS staining, immunohistochemistry and PCR for T. whipplei were negative in the duodenal biopsies. T. whipplei was isolated from the bronchoalveolar fluid, reinforcing its role as a respiratory pathogen.

Campylobacter fetus bacteremia in a young healthy adult transmitted by khat chewing - Corrected Proof

Carlos Martínez-Balzano, Patrick J. Kohlitz, Preeti Chaudhary, Housam Hegazy — 2011-11-24

Summary: Campylobacter fetus is a pathogen affecting almost exclusively patients with immunosuppression and chronic debilitating diseases. We report the case of a healthy young man with C. fetus bacteremia presenting with fever, hypotension and meningitis. The patient had no exposure to contaminated sources except from khat chewing, which we describe as a possible source of transmission for the first time.

Late hepatitis B virus reactivation after lamivudine prophylaxis interruption in an anti-HBs-positive and anti-HBc-negative patient treated with rituximab-containing therapy - Corrected Proof

2011-11-24

Summary: We describe a case of an anti-HBs-positive patient who experienced hepatitis B reactivation 18 months after the discontinuation of rituximab and after 12 months of lamivudine prophylaxis. The patient carried a hepatitis B genotype D virus harbouring a single immune escape mutation, sT118K. No consensus guidelines regarding the optimal length of treatment or the best elective drug have been defined for antiviral prophylaxis for HBsAg-negative, anti-HBc- and/or anti-HBs-positive patients undergoing immunosuppressive treatment.Screening based on HBV serological markers and HBV DNA testing is a critical issue to recognise hepatitis B reactivation as early as possible. Furthermore, it is of outstanding importance to identify alternative markers (e.g. cccDNA, HBV core related antigen, etc.), that could be predictive of HBV reactivation.

WITHDRAWN: JC Virus in the Irish Population: Significant Increase of Genotype 2 in Immunocompromised Individuals - Corrected Proof

K. Schaffer, N. Sheehy, S. Coughlan, C. Bergin, W.W. Hall — 2009-01-23

The publisher regrets that this article is an accidental duplication of an article that has already been published, doi:10.1016/j.jinf.2005.11.042. The duplicate article has therefore been withdrawn.

WITHDRAWN: What is the Clinical Relevance of Laboratory Reported Antibiotic Resistance to Trimethoprim in Primary Care Urinary Tract Infections? - Corrected Proof

2008-12-29

The publisher regrets that this article is an accidental duplication of an article that has already been published, doi:10.1016/j.jinf.2005.11.042. The duplicate article has therefore been withdrawn.

WITHDRAWN: Systematic Analysis of Alkaline Adaptation in Saccharomyces Cerevisiae - Corrected Proof

2008-12-29

The publisher regrets that this article is an accidental duplication of an article that has already been published, doi:10.1016/j.jinf.2005.11.042. The duplicate article has therefore been withdrawn.