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Results 1-18 (18)
 

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Year of Publication
1.  Antifungal wound penetration of amphotericin and voriconazole in combat-related injuries: case report 
BMC Infectious Diseases  2015;15:184.
Background
Survivors of combat trauma can have long and challenging recoveries, which may be complicated by infection. Invasive fungal infections are a rare but serious complication with limited treatment options. Currently, aggressive surgical debridement is the standard of care, with antifungal agents used adjunctively with uncertain efficacy. Anecdotal evidence suggests that antifungal agents may be ineffective in the absence of surgical debridement, and studies have yet to correlate antifungal concentrations in plasma and wounds.
Case presentation
Here we report the systemic pharmacokinetics and wound effluent antifungal concentrations of five wounds from two male patients, aged 28 and 30 years old who sustained combat-related blast injuries in southern Afghanistan, with proven or possible invasive fungal infection. Our data demonstrate that while voriconazole sufficiently penetrated the wound resulting in detectable effluent levels, free amphotericin B (unbound to plasma) was not present in wound effluent despite sufficient concentrations in circulating plasma. In addition, considerable between-patient and within-patient variability was observed in antifungal pharmacokinetic parameters.
Conclusion
These data highlight the need for further studies evaluating wound penetration of commonly used antifungals and the role for therapeutic drug monitoring in providing optimal care for critically ill and injured war fighters.
doi:10.1186/s12879-015-0918-8
PMCID: PMC4403850  PMID: 25886578
Invasive fungal infection; Pharmacokinetics; Negative-Pressure Wound Therapy; NPWT; Effluent
2.  Hepatitis C testing and re-testing among people attending sexual health services in Australia, and hepatitis C incidence among people with human immunodeficiency virus: analysis of national sentinel surveillance data 
BMC Infectious Diseases  2017;17:740.
Background
Direct acting antivirals are expected to drastically reduce the burden of hepatitis C virus (HCV) in people living with Human Immunodeficiency Virus (HIV). However, rates of HCV testing, re-testing and incident infection in this group remain uncertain in Australia. We assessed trends in HCV testing, re-testing and incident infection among HIV-positive individuals, and evaluated factors associated with HCV re-testing and incident infection.
Methods
The study population consisted of HIV-positive individuals who visited a sexual health service involved in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) between 2007 and 2015. Poisson regression was used to assess trends and to evaluate factors associated with HCV re-testing and incident HCV infection.
Results
There were 9227 HIV-positive individuals included in our testing rate analysis.
Of 3799 HIV-positive/HCV-negative people that attended an ACCESS sexual health service more than once, 2079 (54.7%) were re-tested for HCV and were therefore eligible for our incidence analysis. The rate of HCV testing increased from 17.1 to 51.4 tests per 100 patient years between 2007 and 2015 (p for trend <0.01). Over the same period, HCV re-testing rates increased from 23.9 to 79.7 tests per 100 person years (p for trend <0.01). A clear increase in testing and re-testing began after 2011. Patients who identified as men who have sex with men and those with a history of injecting drug use experienced high rates of HCV re-testing over the course of the study period. Among those who re-tested, 157 incident HCV infections occurred at a rate of 2.5 events per 100 person years. Between 2007 and 2009, 2010–2011, 2012–2013 and 2014–2015, rates of incident HCV were 0.8, 1.5, 3.9 and 2.7 events per 100 person years, respectively (p for trend <0.01). Incident HCV was strongly associated with a history of injecting drug use.
Conclusions
High rates of HCV testing and re-testing among HIV-positive individuals in Australia will assist strategies to achieve HCV elimination through rapid treatment scale up. Continued monitoring of HCV incidence in this population is essential for guiding both HCV prevention and treatment strategies.
Electronic supplementary material
The online version of this article (10.1186/s12879-017-2848-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s12879-017-2848-0
PMCID: PMC5709850  PMID: 29191154
Hepatitis C virus; Human immunodeficiency virus; Sexual health; Australia
3.  A multicentre double-blind randomised controlled trial evaluating the efficacy of daily use of antibacterial mouthwash against oropharyngeal gonorrhoea among men who have sex with men: the OMEGA (Oral Mouthwash use to Eradicate GonorrhoeA) study protocol 
BMC Infectious Diseases  2017;17:456.
Background
Gonorrhoea is one of the most common sexually transmissible infections in men who have sex with men (MSM). Gonorrhoea rates have increased substantially in recent years. There is concern that increasing gonorrhoea prevalence will increase the likelihood of worsening antibiotic resistance in Neisseria gonorrhoeae. A recent randomised controlled trial (RCT) demonstrated that a single-dose of mouthwash has an inhibitory effect against oropharyngeal gonorrhoea. We are conducting the first RCT to evaluate whether daily use of mouthwash could reduce the risk of acquiring oropharyngeal gonorrhoea.
Methods/design
The OMEGA (Oral Mouthwash use to Eradicate GonorrhoeA) study is a double-blind RCT and will be conducted at several sexual health clinics and high caseload General Practice (GP) clinics in Melbourne and Sydney, Australia. A total of 504 MSM attending the participating sites will be recruited. Participants will be randomised to either using ‘Study mouthwash A’ or ‘Study mouthwash B’ for 12 weeks. Study mouthwash A was inhibitory against N. gonorrhoeae in vitro, whereas study mouthwash B was not. Participants will be instructed to rinse and gargle the study mouthwash for 60 seconds every day. The primary outcome is the proportion of participants with oropharyngeal gonorrhoea detected by nucleic acid amplification test by 12 weeks.
Discussion
The results from this trial may provide a novel way to reduce gonorrhoea prevalence and transmission without the use of antibiotics that may be associated with development of resistance. If shown to be effective, the widespread use of mouthwash will reduce the prevalence of oropharyngeal gonorrhoea, which plays key role in driving the emergence of gonococcal antimicrobial resistance through DNA exchange with oral commensal bacteria. The anticipated net effect will be interruption of onward transmission of N. gonorrhoeae within high density sexual networks within MSM populations.
Trial registration
Australian New Zealand Clinical Trials Registry ACTRN12616000247471, registered on 23rd February 2016.
doi:10.1186/s12879-017-2541-3
PMCID: PMC5490220  PMID: 28659133
Men who have sex with men; Sexually transmitted infection; Gonorrhoea; Mouthwash; Prevention; Oropharyngeal; Throat; Topical antiseptics; Prophylaxis
4.  Drug-induced liver injury from antituberculous treatment: a retrospective study from a large TB centre in the UK 
BMC Infectious Diseases  2017;17:231.
Background
We describe drug-induced liver injury (DILI) secondary to antituberculous treatment (ATT) in a large tuberculosis (TB) centre in London; we identify the proportion who had risk factors for DILI and the timing and outcome of DILI.
Methods
We identified consecutive patients who developed DILI whilst on treatment for active TB; patients with active TB without DILI were selected as controls. Comprehensive demographic and clinical data, management and outcome were recorded.
Results
There were 105 (6.9%) cases of ATT-associated DILI amongst 1529 patients diagnosed with active TB between April 2010 and May 2014. Risk factors for DILI were: low patient weight, HIV-1 co-infection, higher baseline ALP, and alcohol intake. Only 25.7% of patients had British or American Thoracic Society defined criteria for liver test (LT) monitoring. Half (53%) of the cases occurred within 2 weeks of starting ATT and 87.6% occurred within 8 weeks. Five (4.8%) of seven deaths were attributable to DILI.
Conclusions
Only a quarter of patients who developed DILI had British or American Thoracic Society defined criteria for pre-emptive LT monitoring, suggesting that all patients on ATT should be considered for universal liver monitoring particularly during the first 8 weeks of treatment.
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-017-2330-z) contains supplementary material, which is available to authorized users.
doi:10.1186/s12879-017-2330-z
PMCID: PMC5366108  PMID: 28340562
Tuberculosis; Drug induced liver injury; Hepatotoxicity; Re-introduction regimen; Risk factors; Liver failure
5.  Oral fosfomycin for treatment of urinary tract infection: a retrospective cohort study 
BMC Infectious Diseases  2016;16:556.
Background
Fosfomycin is increasingly called upon for the treatment of multi drug-resistant (MDR) organisms causing urinary tract infection (UTI). We reviewed oral fosfomycin use for UTI treatment in a large UK hospital. The primary goal was to audit our clinical practice against current national guidelines. Secondary aims were to identify factors associated with treatment failure, and to investigate the potential for using fosfomycin in patients with co-morbidities.
Methods
We retrospectively studied 75 adult patients with UTI who received 151 episodes of treatment with fosfomycin from March 2013 to June 2015. We collected clinical data from our electronic patient record, and microbiology data pre- and post- fosfomycin treatment. We recorded additional data for patients receiving prolonged courses in order to make a preliminary assessment of safety and efficacy. We also reviewed >18,000 urinary tract isolates of Escherichia coli and Klebsiella spp. processed by our laboratory over the final year of our study period to determine the prevalence of fosfomycin resistance.
Results
There was a significant increase in fosfomycin treatment episodes over the course of the study period. Co-morbidities were present in 71 % of patients. The majority had E. coli infection (69 %), of which 59 % were extended spectrum beta-lactamase (ESBL)-producers. Klebsiella infections were more likely than E. coli to fail treatment, and more likely to be reported as fosfomycin resistant in cases of relapse following treatment. There were no adverse events in five patients treated with prolonged fosfomycin. Among all urinary isolates collected over a year, fosfomycin resistance was documented in 1 % of E. coli vs. 19 % of Klebsiella spp. (p < 0.0001).
Conclusions
We report an important role for oral fosfomycin for MDR UTI treatment in a UK hospital population, and based on the findings from this study, we present our own local guidelines for its use. We present preliminary data suggesting that fosfomycin is safe and effective for use in patients with complex comorbidities and over prolonged time periods, but may be less effective against Klebsiella than E. coli.
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-016-1888-1) contains supplementary material, which is available to authorized users.
doi:10.1186/s12879-016-1888-1
PMCID: PMC5057270  PMID: 27729016
Gram-negative; UTI; Escherichia coli; Uropathogens; Urosepsis; Fosfomycin; Antibacterials; Antibacterial resistance
6.  Multi-complexity measures of heart rate variability and the effect of vasopressor titration: a prospective cohort study of patients with septic shock 
BMC Infectious Diseases  2016;16:551.
Background
Septic shock is a common and often devastating syndrome marked by severe cardiovascular dysfunction commonly managed with vasopressors. Whether markers of heart rate complexity before vasopressor up-titration could be used to predict success of the up-titration is not known.
Methods
We studied patients with septic shock requiring vasopressor, newly admitted to the intensive care unit. We measured the complexity of heart rate variability (using the ratio of fractal exponents from detrended fluctuation analysis) in the 5 min before all vasopressor up-titrations in the first 24 h of an intensive care unit (ICU) admission. A successful up-titration was defined as one that did not require further up-titration (or decrease in mean arterial pressure) for 60 min.
Results
We studied 95 patients with septic shock, with a median APACHE II of 27 (IQR: 20–37). The median number of up-titrations, normalized to 24 h, was 12.2 (IQR: 8–17) with a maximum of 49. Of the up-titrations, the median proportion of successful interventions was 0.28 (IQR: 0.12–0.42). The median of mean arterial pressure (MAP) at the time of a vasopressor up-titration was 66 mmHg; the average infusion rate of norepinephrine at the time of an up-titration was 0.11 mcg/kg/min. The ratio of fractal exponents was not associated with successful up-titration on univariate or multivariate regression. On exploratory secondary analyses, however, the long-term fractal exponent was associated (p = 0.003) with success of up-titration. Independent of heart rate variability, MAP was associated (p < 0.001) with success of vasopressor up-titration, while neither Sequential Organ Failure Assessment (SOFA) nor Acute Physiology and Chronic Health Evaluation II (APACHE II) score was associated with vasopressor titration.
Conclusions
Only a third of vasopressor up-titrations were successful among patients with septic shock. MAP and the long-term fractal exponent were associated with success of up-titration. These two, complementary variables may be important to the development of rational vasopressor titration protocols.
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-016-1896-1) contains supplementary material, which is available to authorized users.
doi:10.1186/s12879-016-1896-1
PMCID: PMC5057204  PMID: 27724850
Sepsis; Shock; Physiological Variability; Heart Rate Variability
7.  The impact of healthcare visit timing on reported pertussis cough duration: Selection bias and disease pattern from reported cases in Michigan, USA, 2000–2010 
BMC Infectious Diseases  2016;16:522.
Background
Pertussis is a potentially serious respiratory illness characterized by cough of exceptionally long duration of up to approximately100 days. While macrolide antibiotics are an effective treatment, there is an ongoing debate whether they also shorten the length of cough symptoms. We investigated whether public health surveillance data for pertussis, in which cases are identified at diagnosis, are potentially affected by selection bias and the possible consequences for reported cough duration.
Methods
Data on 4,794 pertussis cases reported during 2000–2010 were extracted from the Michigan Disease Surveillance System, a statewide, web-based communicable disease reporting system, to specifically investigate increased duration of cough observed in pertussis patients with delayed initial healthcare visit. A simulated population of cases was derived from the observed surveillance data and truncated week-by-week to evaluate the effects of bias associated with stratification on timing of antibiotics.
Results
Cases presenting for medical evaluation later in the clinical course were more likely to have experienced delayed antibiotic therapy and longer average cough duration. A comparable magnitude of increasing cough duration was also observed in the simulated data. By stratifying on initial medical visit, selection bias effects based on timing of healthcare visit were demonstrated.
Conclusions
Stratifying or controlling for the timing of the initial case identification and accompanying antibiotic treatment can create artificial patterns of observed cough duration. In surveillance data, differences in symptom duration may arise from selection bias and should not be presumed to be related to early antibiotic treatment.
doi:10.1186/s12879-016-1852-0
PMCID: PMC5041436  PMID: 27682251
Pertussis; Cough; Antibiotics; Epidemiology; Selection bias
8.  An open-label, pragmatic, randomized controlled clinical trial to evaluate the comparative effectiveness of daptomycin versus vancomycin for the treatment of complicated skin and skin structure infection 
BMC Infectious Diseases  2015;15:503.
Background
Treatment of complicated skin and skin structure infection (cSSSI) places a tremendous burden on the health care system. Understanding relative resource utilization associated with different antimicrobials is important for decision making by patients, health care providers, and payers.
Methods
The authors conducted an open-label, pragmatic, randomized (1:1) clinical study (N = 250) to compare the effectiveness of daptomycin with that of vancomycin for treatment of patients hospitalized with cSSSI caused by suspected or documented methicillin-resistant Staphylococcus aureus infection. The primary study end point was infection-related length of stay (IRLOS). Secondary end points included health care resource utilization, cost, clinical response, and patient-reported outcomes. Patient assessments were performed daily until the end of antibiotic therapy or until hospital discharge, and at 14 days and 30 days after discharge.
Results
No difference was found for IRLOS, total LOS, and total inpatient cost between cohorts. Hospital LOS contributed 85.9 % to the total hospitalization cost, compared with 6.4 % for drug costs. Daptomycin showed a nonsignificant trend toward a higher clinical success rate, compared with vancomycin, at treatment days 2 and 3. In the multivariate analyses, vancomycin was associated with a lower likelihood of day 2 clinical success (odds ratio [OR] = 0.498, 95 % confidence interval [CI], 0.249–0.997; P < 0.05).
Conclusion
This study did not provide conclusive evidence of the superiority of one treatment over the other in terms of clinical, economic, or patient outcomes. The data suggest that physician and patient preference, rather than drug acquisition cost, should be the primary driver of initial antibiotic selection for hospitalized patients with cSSSI.
Trial registration
ClinicalTrials.gov: NCT01419184 (Date: August 16, 2011)
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-015-1261-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s12879-015-1261-9
PMCID: PMC4637139  PMID: 26547411
Daptomycin; Vancomycin; Complicated skin and skin structure infection; Pragmatic randomized clinical trial; Antimicrobial; Effectiveness
9.  Improving chlamydia knowledge should lead to increased chlamydia testing among Australian general practitioners: a cross-sectional study of chlamydia testing uptake in general practice 
BMC Infectious Diseases  2014;14:584.
Background
Female general practitioners (GPs) have higher chlamydia testing rates than male GPs, yet it is unclear whether this is due to lack of knowledge among male GPs or because female GPs consult and test more female patients.
Methods
GPs completed a survey about their demographic details and knowledge about genital chlamydia. Chlamydia testing and consultation data for patients aged 16-29 years were extracted from the medical records software for each GP and linked to their survey responses. Chi-square tests were used to determine differences in a GP’s knowledge and demographics. Two multivariable models that adjusted for the gender of the patient were used to investigate associations between a GP and their chlamydia testing rates ― Model 1 included GPs’ characteristics such as age and gender, Model 2 excluded these characteristics to specifically examine any associations with knowledge.
Results
Female GPs were more likely than male GPs to know when to re-test a patient after a negative chlamydia test (18.8% versus 9.7%, p = 0.01), the correct symptoms suggestive of PID (80.5% versus 67.8%, p = 0.01) and the correct tests for diagnosing PID (57.1% versus 42.6%, p = 0.01). Female GPs tested 6.5% of patients, while male GPs tested 2.2% (p < 0.01). Model 1 found factors associated with chlamydia testing were being a female GP (OR = 2.5, 95% CI: 1.9, 3.3) and working in a metropolitan clinic (OR = 3.2; 95% CI: 2.4, 4.3). Model 2 showed that chlamydia testing increased as knowledge of testing guidelines improved (3-5 correct answers – AOR = 2.0, 95% CI: 1.0, 4.2; 6+ correct answers – AOR = 2.9, 95% CI: 1.4, 6.2).
Conclusions
Higher rates of chlamydia testing are strongly associated with GPs who are female, based in a metropolitan clinic and among those with more knowledge of the recommended guidelines. Improving chlamydia knowledge among male GPs may increase chlamydia testing.
doi:10.1186/s12879-014-0584-2
PMCID: PMC4228271  PMID: 25409698
Chlamydia testing; General practice; Sexual health knowledge; General practitioner education
10.  Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response 
BMC Infectious Diseases  2014;14:314.
Background
Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population.
Methods
We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-γ ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis.
Results
One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-γ ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A.
Conclusion
The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies.
Trial registration
ClinicalTrials.gov number NCT00953927
doi:10.1186/1471-2334-14-314
PMCID: PMC4061512  PMID: 24912498
Tuberculosis; Vaccine; Innate immunity; Transcriptomics; MVA85A
12.  STI in remote communities: improved and enhanced primary health care (STRIVE) study protocol: a cluster randomised controlled trial comparing ‘usual practice’ STI care to enhanced care in remote primary health care services in Australia 
BMC Infectious Diseases  2013;13:425.
Background
Despite two decades of interventions, rates of sexually transmissible infections (STI) in remote Australian Aboriginal communities remain unacceptably high. Routine notifications data from 2011 indicate rates of chlamydia and gonorrhoea among Aboriginal people in remote settings were 8 and 61 times higher respectively than in the non-Indigenous population.
Methods/design
STRIVE is a stepped-wedge cluster randomised trial designed to compare a sexual health quality improvement program (SHQIP) to usual STI clinical care delivered in remote primary health care services. The SHQIP is a multifaceted intervention comprising annual assessments of sexual health service delivery, implementation of a sexual health action plan, six-monthly clinical service activity data reports, regular feedback meetings with a regional coordinator, training and financial incentive payments. The trial clusters comprise either a single community or several communities grouped together based on geographic proximity and cultural ties. The primary outcomes are: prevalence of chlamydia, gonorrhoea and trichomonas in Aboriginal residents aged 16–34 years, and performance in clinical management of STIs based on best practice indicators. STRIVE will be conducted over five years comprising one and a half years of trial initiation and community consultation, three years of trial conditions, and a half year of data analysis. The trial was initiated in 68 remote Aboriginal health services in the Northern Territory, Queensland and Western Australia.
Discussion
STRIVE is the first cluster randomised trial in STI care in remote Aboriginal health services. The trial will provide evidence to inform future culturally appropriate STI clinical care and control strategies in communities with high STI rates.
Trial registration
Australian and New Zealand Clinical Trials Registry ACTRN12610000358044
doi:10.1186/1471-2334-13-425
PMCID: PMC3847940  PMID: 24016143
Aboriginal; Indigenous; Sexually transmitted infections; Chlamydia; Gonorrhoea; Trichomonas; Continuous quality improvement; Protocol; Prevalence; Remote
13.  Human immunodeficiency virus, hepatitis C, and inflammatory biomarkers in individuals with alcohol problems: a cross-sectional study 
BMC Infectious Diseases  2013;13:399.
Background
Assessing whether hepatitis C (HCV) co-infection with human immunodeficiency virus (HIV) is associated with increased inflammation is complex. The liver, integral to inflammatory biomarker synthesis, is compromised by HCV and alcohol abuse. Using single liver-synthesized biomarkers (e.g. C-reactive protein) to represent inflammation may not be appropriate in HIV/HCV co-infection. We hypothesized that 1) detectable HIV/HCV RNA was independently associated with increased inflammation; 2) a composite inflammation measure describes inflammation differently from single inflammatory biomarkers.
Methods
We compared inflammation by HIV/HCV group in a cohort of 361 HIV infected participants from the HIV-Longitudinal Interrelationships of Viruses and Ethanol study. Inflammatory biomarkers >75th percentile were considered elevated. Associations between HIV/HCV group and elevated biomarkers were analyzed as a composite measure (inflammatory burden) or individually. We defined inflammatory burden as number of concurrently elevated biomarkers. Biomarkers included interleukin-6 (IL-6), C-reactive protein (CRP), cystatin C, serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10). Covariates: alcohol, liver fibrosis, comorbidities, CD4 count, antiretroviral therapy, substance use.
Results
Detectable HIV and HCV RNA (OR = 2.49; 95% CI = 1.05–5.89) and detectable HCV RNA alone (2.95; 1.08–8.01) were independently associated with increased odds of having a greater inflammatory burden compared to undetectable viremia. Elevated IL-10 (7.79; 1.90–31.97) and TNF-α (7.70; 1.42–41.83) were independently associated with detectable HIV and HCV RNA. Elevated IL-10 was also associated with detectable HCV RNA alone (5.51; 1.17, 25.84).
Conclusions
Detectable HIV and HCV replication versus undetectable replication was associated with inflammatory burden and certain inflammatory biomarkers independently of alcohol consumption, liver fibrosis and other comorbidities.
doi:10.1186/1471-2334-13-399
PMCID: PMC3848623  PMID: 23987993
HIV; HCV; Inflammation; Alcohol; Liver; Comorbidity
14.  Estimated health and economic impact of quadrivalent HPV (types 6/11/16/18) vaccination in Brazil using a transmission dynamic model 
BMC Infectious Diseases  2012;12:250.
Background
Cervical cancer is the second most common cancer among women in Brazil. We examined the health and economic impacts of quadrivalent HPV vaccination in Brazil.
Methods
We adapted a previously developed transmission dynamic model to estimate the effectiveness of HPV vaccination on cervical cancer, cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3), CIN1, and genital warts. We evaluated following vaccination strategies: routine vaccination of 12-year-old girls and routine vaccination in combination with a catch-up vaccination of 12 to 26-year-old women.
Results
The model projected that the vaccination would reduce the incidence rates of HPV 6/11/16/18-related cervical cancer, CIN2/3, CIN1, and female genital warts by 94% to 98% at year 100. Routine vaccination in combination with a catch-up vaccination could prevent approximately 163,000 cases of cervical cancer, 48,000 deaths from cervical cancer, 2.3 million cases of CIN2/3, and 11.4 million genital warts in the next 50 years. The incremental cost-effectiveness ratios for female vaccination strategies ranged from R$350 to R$720 (US$219 to US$450) per quality-adjusted life year (QALY) gained.
Conclusions
Our study demonstrates that quadrivalent HPV female vaccination can be a cost-effective public health intervention that can substantially reduce the burden of cervical diseases and genital warts in Brazil.
doi:10.1186/1471-2334-12-250
PMCID: PMC3517904  PMID: 23046886
15.  Outbreak of Pneumonia in the Setting of Fatal Pneumococcal Meningitis among US Army Trainees: Potential Role of Chlamydia pneumoniae Infection 
BMC Infectious Diseases  2011;11:157.
Background
Compared to the civilian population, military trainees are often at increased risk for respiratory infections. We investigated an outbreak of radiologically-confirmed pneumonia that was recognized after 2 fatal cases of serotype 7F pneumococcal meningitis were reported in a 303-person military trainee company (Alpha Company).
Methods
We reviewed surveillance data on pneumonia and febrile respiratory illness at the training facility; conducted chart reviews for cases of radiologically-confirmed pneumonia; and administered surveys and collected nasopharyngeal swabs from trainees in the outbreak battalion (Alpha and Hotel Companies), associated training staff, and trainees newly joining the battalion.
Results
Among Alpha and Hotel Company trainees, the average weekly attack rates of radiologically-confirmed pneumonia were 1.4% and 1.2% (most other companies at FLW: 0-0.4%). The pneumococcal carriage rate among all Alpha Company trainees was 15% with a predominance of serotypes 7F and 3. Chlamydia pneumoniae was identified from 31% of specimens collected from Alpha Company trainees with respiratory symptoms.
Conclusion
Although the etiology of the outbreak remains unclear, the identification of both S. pneumoniae and C. pneumoniae among trainees suggests that both pathogens may have contributed either independently or as cofactors to the observed increased incidence of pneumonia in the outbreak battalion and should be considered as possible etiologies in outbreaks of pneumonia in the military population.
doi:10.1186/1471-2334-11-157
PMCID: PMC3121612  PMID: 21635754
Pneumonia; pneumococcal; Chlamydophila; pneumoniae; Military Personnel
16.  Secular trends of antimicrobial resistance of blood isolates in a newly founded Greek hospital 
Background
Antimicrobial resistance is one of the most challenging issues in modern medicine.
Methods
We evaluated the secular trends of the relative frequency of blood isolates and of the pattern of their in vitro antimicrobial susceptibility in our hospital during the last four and a half years.
Results
Overall, the data regarding the relative frequency of blood isolates in our newly founded hospital do not differ significantly from those of hospitals that are functioning for a much longer period of time. A noteworthy emerging problem is the increasing antimicrobial resistance of Gram-negative bacteria, mainly Acinetobacter baumannii and Klebsiella pneumoniae to various classes of antibiotics. Acinetobacter baumannii isolates showed an increase of resistance to amikacin (p = 0.019), ciprofloxacin (p = 0.001), imipenem (p < 0.001), and piperacillin/tazobactam (p = 0.01) between the first and second period of the study.
Conclusion
An alarming increase of the antimicrobial resistance of Acinetobacter baumannii isolates has been noted during our study.
doi:10.1186/1471-2334-6-99
PMCID: PMC1513235  PMID: 16776825
17.  Outcome of infections due to pandrug-resistant (PDR) Gram-negative bacteria 
Background
The increasing problem of infections due to multidrug-resistant Gram-negative bacteria has led to re-use of polymyxins in several countries. However, there are already clinical isolates of Gram-negative bacteria that are resistant to all available antibiotics, including polymyxins.
Methods
We present a case series of patients with infections due to pathogens resistant to all antimicrobial agents tested, including polymyxins. An isolate was defined as pandrug-resistant (PDR) if it exhibited resistance to all 7 anti-pseudomonal antimicrobial agents, i.e. antipseudomonal penicillins, cephalosporins, carbapenems, monobactams, quinolones, aminoglycosides, and polymyxins.
Results
Clinical cure of the infection due to pandrug-resistant (PDR) Gram-negative bacteria, namely Pseudomonas aeruginosa or Klebsiella pneumoniae was observed in 4 out of 6 patients with combination of colistin and beta lactam antibiotics.
Conclusion
Colistin, in combination with beta lactam antibiotics, may be a useful agent for the management of pandrug-resistant Gram-negative bacterial infections. The re-use of polymyxins, an old class of antibiotics, should be done with caution in an attempt to delay the rate of development of pandrug-resistant Gram-negative bacterial infections.
doi:10.1186/1471-2334-5-24
PMCID: PMC1087841  PMID: 15819983
18.  Toxicity after prolonged (more than four weeks) administration of intravenous colistin 
Background
The intravenous use of polymyxins has been considered to be associated with considerable nephrotoxicity and neurotoxicity. For this reason, the systemic administration of polymyxins had been abandoned for about 20 years in most areas of the world. However, the problem of infections due to multidrug-resistant (MDR) Gram-negative bacteria such us Pseudomonas aeruginosa and Acinetobacter baumanniii has led to the re-use of polymyxins. Our objective was to study the toxicity of prolonged intravenous administration of colistin (polymyxin E).
Methods
An observational study of a retrospective cohort at "Henry Dunant" Hospital, a 450-bed tertiary care center in Athens, Greece, was undertaken.
Patients who received intravenous colistin for more than 4 weeks for the treatment of multidrug resistant Gram-negative infections were included in the study. Serum creatinine, blood urea, liver function tests, symptoms and signs of neurotoxicity were the main outcomes studied.
Results
We analyzed data for 19 courses of prolonged intravenous colistin [mean duration of administration (± SD) 43.4 (± 14.6) days, mean daily dosage (± SD) 4.4 (± 2.1) million IU, mean cumulative dosage (± SD) 190.4 (± 91.0) million IU] in 17 patients. The median creatinine value increased by 0.25 mg/dl during the treatment compared to the baseline (p < 0.001) but returned close to the baseline at the end of treatment (higher by 0.1 mg/dl, p = 0.67). No apnea or other evidence of neuromuscular blockade was noted in any of these patients who received prolonged treatment with colistin.
Conclusions
No serious toxicity was observed in this group of patients who received prolonged intravenous colistin. Colistin should be considered as a therapeutic option in patients with infections due to multidrug resistant Gram-negative bacteria.
doi:10.1186/1471-2334-5-1
PMCID: PMC547910  PMID: 15642116

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