Microbial Cause Research Articles

Aetiology of hospital-acquired pneumonia and trends in antimicrobial resistance

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) continue to present very significant diagnostic and management challenges. The development, introduction and use of a wider range of immunosuppressive therapies are leading to a broader spectrum of microorganisms causing HAP and VAP. The persistent clinical dilemma regarding their cause is that detection of a microorganism from a respiratory tract sample does not necessarily signify it is the causative agent of the pneumonia. The ever-increasing antibiotic resistance problem means that HAP and VAP are becoming progressively more difficult to treat. In this article, we review the cause, antimicrobial resistance, diagnosis and treatment of HAP and VAP and encapsulate recent developments and concepts in this rapidly moving field. Although the microbial causes of HAP and VAP remain at present similar to those identified in previous studies, there are marked geographical differences. Resistance rates among Gram-negative bacteria are continually increasing, and for any species, multiresistance is the norm rather than the exception. The development and introduction of rapid point-of-care diagnostics may improve understanding of the cause of HAP and VAP and has immense potential to influence the treatment and clinical outcomes in HAP/VAP, with patients likely to receive much faster, microorganism-specific treatment with obvious downstream improvements to clinical outcome and antimicrobial stewardship. We describe recent trends in aetiology of HAP and VAP and recent trends in antimicrobial resistance, including resistance mechanisms causing particular concern. The potential for novel molecular diagnostics to revolutionize the diagnosis and treatment of HAP/VAP is discussed.

A probabilistic quantitative microbial risk assessment model of norovirus disease burden from wastewater irrigation of vegetables in Shepparton, Australia

Wastewater can be an important resource for water-scarce regions of the world, but a major barrier to its use is the associated health risk. Quantitative microbial risk assessment (QMRA) is a probabilistic modeling technique used to determine the health risks from wastewater reuse, but only a handful of QMRA studies have examined the norovirus health risks from consumption of vegetables irrigated with human wastewater, even though norovirus is a, if not the most, significant microbial cause of diarrheal disease world-wide. Furthermore, the majority of these studies have focused only on risks from lettuce consumption. To meet the knowledge gap in health risks for other vegetables, a QMRA model was constructed for agricultural wastewater irrigation in the regional city of Shepparton, Australia, using fecal shedding rates to estimate norovirus concentration in raw sewage. Annual norovirus disease burden was estimated for the consumption of lettuce, broccoli, cabbage, Asian vegetables, and cucumber after irrigation with treated wastewater. Results indicate that the waste stabilization pond treatment did not have sufficient virus removal to meet the World Health Organization (WHO) threshold for acceptable level of risk for wastewater reuse, but addition of disinfection treatments provided acceptable results for consumption of cucumber and broccoli. This is the first QMRA study to incorporate virus accumulation from previous wastewater irrigation events.

Drug-resistant ventilator associated pneumonia in a tertiary care hospital in Saudi Arabia.

BACKGROUND:There is a wide geographic and temporal variability of bacterial resistance among microbial causes of ventilator-associated pneumonia (VAP). The contribution of multi-drug resistant (MDR) pathogens to the VAP etiology in Saudi Arabia was never studied. We sought to examine the extent of multiple-drug resistance among common microbial causes of VAP.MATERIALS AND METHODS:We conducted a retrospective susceptibility study in the adult intensive care unit (ICU) of King Abdulaziz Medical City, Riyadh, Saudi Arabia. Susceptibility results of isolates from patients diagnosed with VAP between October 2004 and June 2009 were examined. The US National Healthcare Safety Network definition of MDR was adopted.RESULTS:A total of 248 isolates including 9 different pathogens were included. Acinetobacter spp. was highly (60-89%) resistant to all tested antimicrobials, including carbapenems (three- and four-class MDR prevalence were 86% and 69%, respectively). Pseudomonas aeruginosa was moderately (13-31%) resistant to all tested antimicrobials, including antipseudomonal penicillins (three- and four-class MDR prevalence were 13% and 10%, respectively). With an exception of ampicillin (fully resistant), Klebsiella spp. had low (0-13%) resistance to other tested antimicrobials with no detected MDR. Staphylococcus aureus was fully susceptible to vancomycin with 42% resistance to oxacillin. There were significant increasing trends of MDR Acinetobacter spp. however not P. aeruginosa during the study. Resistant pathogens were associated with worse profile of ICU patients but not patients’ outcomes.CONCLUSION:Acinetobacter in the current study was an increasingly resistant VAP-associated pathogen more than seen in many parts of the world. The current finding may impact local choice of initial empiric antibiotics.

Complicated Skin and Skin Structure Infections (cSSSI’s): A Comprehensive Review

Complicated skin and skin structure infections (cSSSI’s) are among the most common microbial infections occurring both in the community and the hospitals. Aetiology of cSSSI’s is complex and includes various microorganisms (bacteria, fungi, parasites and viruses). cSSSI’s in general are poly microbial in nature including both anaerobic and aerobic bacterial species. Primary cSSSI’s resulting from single bacterial species and secondary bacterial infections in patients suffering from skin conditions due to autoimmune conditions (eczema) or other microbial causes (viruses, fungi and parasites) have been reported in the literature. Occurrence of multi-drug resistant bacteria, underlying co-morbidities contribute to the complications in the management of cSSSI’s. Formulating effective guidelines for clinical, laboratory diagnosis, treatment and management of patients suffering from cSSSI’s would certainly be beneficial in the reduction of morbidity and mortality.

Underlying heart disease and microbiological spectrum of adult infective endocarditis in one Chinese university hospital: a 10‐year retrospective study

To identify the underlying heart disease and microbiological pathogen associated with infective endocarditis (IE) in Chinese patients in one university hospital over a 10-year period. We recruited 115 adult patients admitted to Peking University First Hospital from 2002 to 2011 who were diagnosed with definite IE. Statistical analysis was performed to analyse data on demographics, clinical and laboratory findings, as well as microbiological pathogens. The most common underlying heart diseases for IE were congenital heart disease (24.3%) followed by degenerative valvular disease (17.4%). Aortic (44.3%) and mitral (43.5%) valves were most frequently affected. The right-sided IE cases were all found in patients with congenital heart disease. The age of patients was younger in right-sided cases than that in left-sided ones (P = 0.001). There was no difference in the mortality among groups with different underlying heart disease (P = 0.841). Forty-four (38.3%) patients were infected with viridans group streptococci. The isolation rate of staphylococci in right-sided IE was higher than that in the left-sided IE group (P = 0.021). More than 85% of streptococci were susceptible to β-lactams. Congenital heart disease and degenerative valvular disease have overtaken rheumatic heart disease as the major underlying heart diseases associated with IE. Viridans group streptococci are the most common microbial cause of IE.

Descriptive analysis of patients with cellulitis in a second level hospital

revealed amucocutaneousKaposi sarcoma. TheKS lesion cells showed a high positivity of CD31, CD34, and HHV-8 immunoreactivities. Viral serology (HIV, hepatitis B and C virus, Epstein–Barr virus and cytomegalovirus) was negative. The diagnosis of HHV8 infection responsible for HLS as well as for KS was retained. Comments: HLS is a severe life-threatening disorder which can be associated to malignancies, to autoimmunes disorders and to infections. Herpes viruses are the most frequent microbial cause of HLS in more than half of the cases. On the other hand, HHV8 is the principal pathogenesis factor of KS, since over 95% of KS lesions, regardless of their clinical type, have been found to be infected with HHV-8. According to our review of the previous literatures there are few cases of HLS associated with a KS.

Impact of Age and Comorbidity on Cause and Outcome in Community-Acquired Pneumonia

Prolonged life expectancy has currently increased the proportion of the very elderly among patients with community-acquired pneumonia (CAP). The aim of this study was to determine the influence of age and comorbidity on microbial patterns in patients over 65 years of age with CAP. This study was a prospective observational study of adult patients with CAP (excluding those in nursing homes) over a 12-year period. We compared patients aged 65 to 74 years, 75 to 84 years, and > 85 years for potential differences in clinical presentation, comorbidities, severity on admission, microbial investigations, causes, antimicrobial treatment, and outcomes. We studied a total of 2,149 patients: 759 patients (35.3%) aged 65 to 74 years, 941 patients (43.7%) aged 75 to 84 years, and 449 patients (20.8%) aged > 85 years. At least one comorbidity was present in 1,710 patients (79.6%). Streptococcus pneumoniae was the most frequent pathogen in all age groups, regardless of comorbidity. Staphylococcus aureus, Enterobacteriaceae, and Pseudomonas aeruginosa accounted for 9.1% of isolates, and Haemophilus influenzae, 6.4%. All these pathogens were isolated only in patients with at least one comorbidity. Mortality increased with age (65-74 years, 6.9%; 75-84 years, 8.9%; > 85 years, 17.1%; P < .001) and was associated with increased comorbidities (neurologic; OR, 2.1; 95% CI, 1.5-2.1), Pneumonia Severity Index IV or V (OR, 3.2; 95% CI, 1.8-6.0), bacteremia (OR, 1.7; 95% CI, 1.1-2.7), the presence of a potential multidrug-resistant (MDR) pathogen (S. aureus, P. aeruginosa, Enterobacteriaceae; OR, 2.4; 95% CI, 1.3-4.3), and ICU admission (OR, 4.2; 95% CI, 2.9-6.1) on multivariate analysis. Age does not influence microbial cause itself, whereas comorbidities are associated with specific causes such as H. influenzae and potential MDR pathogens. Mortality in the elderly is mainly driven by the presence of comorbidities and potential MDR pathogens.

A patient with acute pancreatitis and unusual vermiform stools

A 66-year-old woman was admitted with severe pancreatitis of unknown aetiology. Medical history disclosed insulin-dependent diabetes. She was treated conservatively with fluid and electrolyte correction. The patient was haemodynamically stable...

Erratum:A patient with acute pancreatitis and unusual vermiform stools

A 66-year-old woman was admitted with severe pancreatitis of unknown aetiology. Medical history disclosed insulin-dependent diabetes. She was treated conservatively with fluid and electrolyte correction. The patient was haemodynamically stable throughout the disease course. On day 4 she developed a paralytic ileus. Parenteral nutrition was initiated. Gradually, the ileus resolved. Enteral feeding was resumed on day 13 via a nasojejunal feeding tube. Over the following days, the patient developed watery diarrhoea. PCR and cultures failed to demonstrate a microbial cause. Suddenly, at day 21, the patient excreted per …

Abstract 4149: Transcriptomic and pathogen analysis in bladder cancer primary tumor and metastasis pairs.

Abstract Urothelial carcinoma (also called transitional cell carcinoma, most commonly of the bladder) is the fourth leading cause of new cancers in men in the United States, and accounts for 13,000 deaths per year. Five-year survival for patients with muscle invasive disease is below 50%. Both genetic mutations and epigenetic events are important in urothelial cancer pathogenesis and prognosis, and environmental triggers such as Schistosoma infection and tobacco have been identified. In this study we have undertaken a transcriptomic analysis of fourteen paired primary tumors and distant metastases in order to identify mutations and potential pathogenic viruses that may play a role in the pathogenesis of urothelial cancer. The contribution of infections to urothelial cancer pathogenesis remains a hotly contested issue with data both supporting and refuting the role of polyomaviruses in the disease. Recently, our colleagues at the Broad Institute discovered a striking similarity in DNA mutation pattern between cervical cancer, which is virally driven, and bladder cancer. Based on this finding, we hypothesize that a subset of urothelial cancers are triggered by a microbial pathogen that can be detected using nucleic acid sequencing methods. The majority of clinical translational studies to date have investigated patient urine samples. While these studies have been unsuccessful in identifying a strong candidate microbial trigger of urothelial cancer, direct analysis of tumor tissue for pathogen discovery has not been rigorously pursued. In order to investigate a potential microbial cause of urothelial cancer, we propose undertaking a “deep sequencing” approach where all RNA will be sequenced, followed by taxonomic classification of microbial sequences. In addition to the microbial characterization of these samples, the transcriptomic data will be analyzed to identify disease-associated mutations, fusions and splicing variants of significance in primary and matched metastasis pairs. This study represents an analysis of the largest matched primary tumor-distant metastasis cohort to our knowledge, to date. We anticipate that discovery of a novel pathogen or significant transcriptomic changes that trigger urothelial cancer could dramatically alter clinical management by enabling development of screening methods and protocols, targeted therapies and vaccines. Citation Format: Ami S. Bhatt, Chandra Sekhar Pedamallu, Fujiko Duke, Joonil Jung, Samuel S. Freeman, Andrew Cherniak, Rachel Park, Jaegil Kim, David Kwiatkowski, Jonathan Rosenberg, Matthew Meyerson. Transcriptomic and pathogen analysis in bladder cancer primary tumor and metastasis pairs. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4149. doi:10.1158/1538-7445.AM2013-4149

Acinetobacter is the most common pathogen associated with late-onset and recurrent ventilator-associated pneumonia in an adult intensive care unit in Saudi Arabia

The guidelines for initial empiric antimicrobial therapy for ventilator-associated pneumonia (VAP) are highly dependent on the type of causative pathogen and the time of diagnosis. The objective of this study was to examine the microbial causes of VAP and describe any variability by the timing of VAP onset and over time. A prospective surveillance study was conducted in the adult general intensive care unit of a tertiary care hospital in Riyadh, Saudi Arabia. Microbial isolates obtained from blood and different respiratory specimens of patients diagnosed with VAP (using the US Centers for Disease Control and Prevention definition) between August 2003 and June 2009 were included. A total of 457 pathogens were identified during the study; 380 (83.2%) were associated with primary VAP and 77 (16.8%) were associated with recurrent VAP. Of primary VAP pathogens, 159 (41.8%) were associated with early-onset (<5 days) and 221 (58.2%) were associated with late-onset (≥5 days) VAP. The most common pathogen identified was Acinetobacter spp (26.5%), followed by Pseudomonas aeruginosa (21.7%), Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) (15.3%), Klebsiella spp (6.8%), Haemophilus spp (6.1%), and Enterobacter spp (5.0%). Acinetobacter spp and MRSA were significantly associated with late-onset VAP while Haemophilus spp and Streptococcus pneumoniae were significantly associated with early-onset VAP. Acinetobacter spp was the only pathogen associated with recurrent VAP and its incidence showed a significant increasing trend during the study period. Acinetobacter spp was significantly associated with prolonged ventilation, sedation, and nasogastric intubation. Acinetobacter baumannii is the most common and increasingly important pathogen associated with VAP in our patients, especially late-onset and recurrent VAP.

A clinical laboratory approach to severe sepsis : The changing role of laboratory medicine in clinical decision support during management of septicaemia.

epsis has a different meaning to the surgeon, physician and intensivist than the clinical microbiologist. Understanding the difference between a front line clinician’s diagnosis and determination of the microbial cause of severe sepsis is the key to unlocking the contribution of the clinical laboratory to critical decision support for septicaemic patients. Correct and effective use of blood culture, other culture and non-culture based methods of determining aetiology, followed by monitoring progress in severe sepsis are time-critical support measures for treatment decisions. Nucleic acid amplification techniques and MALDI-TOF mass spectrometer use have sped up the interval between blood culture inoculation and determination of a definitive aetiology. However, the aetiology can only rarely be determined soon enough to direct presumptive antibiotic choice in severe sepsis. More often, presumptive antibiotic and supportive care decisions have to be made with guidance from guidelines, clinical trial results and local laboratory-derived epidemiology. The contribution of the clinical microbiology laboratory is therefore more often in refinement of antibiotic treatment and the monitoring of progress. Until emerging laboratory technology has more to offer in the immediate assessment of severe sepsis, the clinical microbiologist will continue to play a mainly supportive role as a member of a multidisciplinary team. This is likely to change as a range of systems biology tools start to make an impact on the clinical laboratory. DOI: http://dx.doi.org/10.4038/sljid.v3i1.5150

Commentary: cholera conundrums and proto-epidemiologic puzzles. The confusing epidemic world of John Lea and John Snow.

Commentary: cholera conundrums and proto-epidemiologic puzzles. The confusing epidemic world of John Lea and John Snow.

P069: Drug-resistant acinetobacter ventilator-associated pneumonia: a time for desperate measures!

There is a wide geographic and temporal variability of bacterial resistance among microbial causes of ventilator-associated pneumonia (VAP). The contribution of multi-drug resistant (MDR) pathogens to the VAP etiology in Saudi Arabia was never studied.

The cystic fibrosis airway microbiome

Culture and molecular approaches have established that lower airway infections are polymicrobial. We consider how this new perspective in cystic fibrosis (CF) may affect treatment choices. Standard clinical microbiology of CF infection exacerbations often fails to provide indications of microbial causes that may drive the onset of exacerbation and the anticipated bacteriologic responses to the usual parenteral antibiotics prescribed as treatment. Antimicrobial responses by nonclassical members of the CF airway microbiome may explain why most patients clinically improve. These other organisms contribute to disease either directly as pathogens missed by conventional microbiology or through synergy with conventional pathogens. With these considerations, therapy may best be guided by directed antibiotic therapy to numerically significant isolates. An example is the Streptococcus milleri group, which we now believe to represent new pathogens that profile the exacerbations of infection in the CF lung and that necessitate specific antibiotic therapy to prevent loss of lung function and reduce frequency of exacerbations. A comprehensive understanding of airway infections offers the potential for improved disease management in CF patients. Accurate quantitative microbiology will be a prerequisite for routine intervention based on the polymicrobial perspective of CF infection exacerbations.

Incidence of Alpha‐Herpes virus induced ocular disease in Suriname

Herpes simplex virus (HSV) infection of the corneal stroma is the most prominent cause of scar formation impairing visual acuity and HSV keratitis is the leading cause of corneal opacity throughout the world. Suriname lacked test systems for microbial causes of ocular disease, therefore a polymerase chain reaction-based Herpes virus assay was introduced, enabling prompt recognition, and timely treatment, preventing progressive eye damage. The incidence and epidemiology of Herpes simplex virus type 1 (HSV-1), type 2 (HSV-2), and varicella zoster virus (VZV) in ocular disease in Suriname was assessed. In a cross-sectional prospective study, ocular swabs were collected from 91 patients with a presumptive α-Herpes virus ocular infection attending the Academic Hospital between November 2008 and August 2010 and were tested by a PCR-based α-Herpes virus assay. Alpha-Herpes virus ophthalmic infections were caused predominantly by HSV-1 with a prevalence of 31%. The prevalences of VZV, HSV-2, and a mixed HSV-1/HSV-2 infection were 4%, 3%, and 2%, respectively. The first reported annual incidence of herpetic induced ocular disease in Suriname was estimated at 11.4 per 100,000 person-years (95% CI, 4.8-18.1). No clear age, ethnic or gender dependent difference in incidence was observed. The information obtained on α-Herpes virus positive ocular infections and the distribution of subtypes provided the first insight in the South American situation of α-Herpes virus induced ocular disease.

Whooping Cough: A Brief History to the 19th Century.

This paper examines the history of whooping cough (pertussis) from its first recorded mention in 1190 to the time when its microbial cause was identified. The historical records of the disease are complicated by the variation in the nomenclature employed and through using the same name for disorders with different symptoms. During the early-modern period it was considered to be a disease new to Europe-contagious, dangerous, and potentially epidemic. Believed to be confined to children, its significance was limited until the 18th century when its incidence increased markedly. This essay argues pertussis may have occurred in the late medieval period in individual, though not epidemical, cases.

Infectious Disease Management through Point-of-Care Personalized Medicine Molecular Diagnostic Technologies.

Infectious disease management essentially consists in identifying the microbial cause(s) of an infection, initiating if necessary antimicrobial therapy against microbes, and controlling host reactions to infection. In clinical microbiology, the turnaround time of the diagnostic cycle (>24 hours) often leads to unnecessary suffering and deaths; approaches to relieve this burden include rapid diagnostic procedures and more efficient transmission or interpretation of molecular microbiology results. Although rapid nucleic acid-based diagnostic testing has demonstrated that it can impact on the transmission of hospital-acquired infections, we believe that such life-saving procedures should be performed closer to the patient, in dedicated 24/7 laboratories of healthcare institutions, or ideally at point of care. While personalized medicine generally aims at interrogating the genomic information of a patient, drug metabolism polymorphisms, for example, to guide drug choice and dosage, personalized medicine concepts are applicable in infectious diseases for the (rapid) identification of a disease-causing microbe and determination of its antimicrobial resistance profile, to guide an appropriate antimicrobial treatment for the proper management of the patient. The implementation of point-of-care testing for infectious diseases will require acceptance by medical authorities, new technological and communication platforms, as well as reimbursement practices such that time- and life-saving procedures become available to the largest number of patients.

A literature review and survey of childhood pneumonia etiology studies: 2000-2010.

The Pneumonia Etiology Research for Child Health (PERCH) project is the largest multicountry etiology study of childhood pneumonia since the Board on Science and Technology in International Development studies of the 1980s. However, it is not the only recent or ongoing pneumonia etiology study, and even with seven sites, it cannot capture all epidemiologic settings in the developing world. Funding providers, researchers and policymakers rely on the best available evidence to strategically plan programs, new research directions and interventions. We aimed to describe the current landscape of recent pneumonia etiology studies in children under 5 years of age in the developed and developing world, as ascertained by a literature review of relevant studies with data since the year 2000 and a survey of researchers in the field of childhood pneumonia. We collected information on the study population, study design, case definitions, laboratory samples and methods and identified pathogens. A literature review identified 88 studies with child pneumonia etiology results. As of June 2010, our survey of researchers identified an additional 65 ongoing and recently completed child pneumonia etiology studies. This demonstrates the broad existing context into which the PERCH study must be placed. However, the landscape analysis also reveals a multiplicity of case definitions, levels of clinician involvement, facility types, specimen collection, and laboratory techniques. It reinforces the need for the standardization of methods and analyses for present and future pneumonia etiology studies in order to optimize their cumulative potential to accurately describe the microbial causes of childhood pneumonia.

Childhood Pneumonia as a Global Health Priority and the Strategic Interest of The Bill &amp; Melinda Gates Foundation

Pneumonia kills more children than any other disease--more than HIV/AIDS, malaria, and measles combined. Introduction of vaccines against pneumococcus and Haemophilus influenzae type b (the most important causes of severe pneumonia in young children), increasing resistance to antibiotics, and changes in HIV prevalence will likely change patterns of pneumonia etiology in developing countries. Studies such as Pneumonia Etiology Research for Child Health (PERCH) that take advantage of new diagnostic technologies are needed to provide an updated and more precise description of the microbial causes of pneumonia and to inform decisions around treatment algorithms and vaccine development and introduction. In recognition of its importance for global health and especially its significance as an ongoing cause of gross inequity in risks, The Bill & Melinda Gates Foundation has made pneumonia an important part of its global health strategy and PERCH a centerpiece of its Pneumonia Program.