Target product profiles for diagnosis of sepsis: Proposing a new approach for diagnostic innovation

Background & objectives: Sepsis, including neonatal sepsis, remains a prevalent cause of morbidity and mortality in low- and middle-income countries such as India, representing 85 per cent of all sepsis-related deaths globally. Early diagnosis and timely initiation of treatment is challenging due to non-specific clinical manifestations and non-availability of rapid diagnostic tests. There is an urgent need for affordable diagnostics with fast turnaround time catering to the needs of end-users. Target product profiles (TPPs) have been found instrumental in developing ‘fit-for-use’ diagnostics, thus reducing the time taken to facilitate development and improving diagnosis. Hitherto, no such guidance or criteria has been defined for rapid diagnostics for sepsis/neonatal sepsis. We propose an innovative approach for developing the diagnostics for sepsis screening and diagnosis which can be utilized by diagnostic developers in the country. Methods: Three-round Delphi method, including two online surveys and one virtual consultation, was adopted to define criteria for minimum and optimum attributes of TPPs and build consensus on characteristics. Expert panel (n=23) included infectious disease physicians, public health specialists, clinical microbiologists, virologists, researchers/scientists and technology experts/innovators. Results: We present a three-component product profile for sepsis diagnosis, (i) screening with high sensitivity, (ii) detection of aetiological agent, and (iii) profiling of antimicrobial susceptibility/resistance, in adults and neonates with an option of testing different considerations. An agreement of >75 per cent was achieved for all TPP characteristics by Delphi. These TPPs are tailored to the Indian healthcare settings and can also be extrapolated to other resource-constraint and high-disease burden settings.

Mobile thrombus of the abdominal aorta: a narrative review / Trombo móvel de aorta abdominal: uma revisão narrativa

Abstract A primary aortic mural thrombus (PAMT) is defined as a thrombus attached to the aortic wall in the absence of any atherosclerotic or aneurysmal disease of the aorta or any cardiac source of embolus. It is a rare entity that has high morbidity and mortality. There is no consensus on the ideal treatment of PAMT. The objective of this paper is to review the possibilities for treatment of mobile abdominal aortic mural thrombus. Endovascular therapy and open surgery appear to be the best options for treatment of mobile abdominal aortic mural thrombus. Thus, in patients with favorable anatomy, endovascular therapy is probably the treatment choice, while in those with unfavorable anatomy, open surgery is probably the best option for treatment of a mobile abdominal aortic thrombus. It is important to emphasize that anticoagulation alone can be used as a non-aggressive option and, if this fails, endovascular or surgical methods can then be employed.

Resumo O trombo mural aórtico primário é definido como um trombo aderido à parede aórtica na ausência de doença aterosclerótica e/ou aneurismática ou de fonte cardíaca de êmbolo. Trata-se de uma doença rara, porém causadora de alta morbimortalidade, e não há consenso acerca do seu tratamento. Este estudo objetivou revisar as possibilidades na presença de componente móvel. A terapia endovascular e a cirurgia aberta parecem ser as melhores opções, sendo a abordagem endovascular o tratamento de escolha para pacientes com anatomia favorável e a cirurgia aberta o tratamento de escolha para pacientes com anatomia desfavorável. No entanto, a anticoagulação sistêmica apresenta-se como método não invasivo para pacientes com alto risco cirúrgico e como possibilidade terapêutica na falha ou indisponibilidade de abordagem cirúrgica.

Association between diagnosis, clinical outcome and hospitalization time of the elderly in a university hospital / Associação entre diagnóstico, desfecho clínico e tempo de internação de idosos em um hospital escola

Clinical outcomes of hospitalized elderly provide subsidies to prevent complications that interfere with quality of life.The goal was to verify the sociodemographic characteristics and to analyze the associations between the diseasesdiagnosed at admission, age, hospitalization time and clinical outcome of elderly hospitalized in SUS and private care.Descriptive and quantitative cross-sectional survey of 14,892 medical records of elderly patients hospitalized in theyear 2014. The statistical tests used were chi-squared and analysis of variance. The results were: 93.5% white, 80.2%catholic, 68% had a primary education, 62.9% had partners, 53.8% males, 33.1% homemakers and the average agewas 72.1 years ± 8.6 years. The mean duration of hospitalization was 5.9 days ± 8.8 days, cardiovascular diseaseswere the most frequent, with a clinical outcome of 93.4% of hospital discharges and 6.6% of deaths, and 100% ofhematological diseases were discharged. There was a significant association rate between diseases and death frominfections (n=817; 60.0%). The association of diseases with the type of SUS care was statistically significant. Moreover,the occurrence of pain, nephro-urological diseases, orthopedic diseases, hematological and gynecological diseasesand other diseases showed a statistically significant association with private care or health plan. The associationbetween the diseases and the clinical outcome showed a greater incidence of death in patients affected by infections.The association of diseases was statistically significant with the type of care, highlighting the SUS care

Os desfechos clínicos de idosos internados proporcionam subsídios para prevenir complicações que interferem naqualidade de vida. O objetivo no estudo foi verificar as características sociodemográficas e analisar as associaçõesentre as doenças diagnosticadas na admissão, idade, tempo de internação e desfecho clínico de idosos internadosno SUS e convênio. Pesquisa transversal, descritiva e quantitativa, nos prontuários eletrônicos de 14.892 idososhospitalizados no ano de 2014. Os testes realizados foram Qui-quadrado e análise de variância. Constatou-se que93,5% eram brancos, 80,2% católicos, 68% possuíam ensino fundamental, 62,9% tinham companheiros, 53,8%homens, 33,1% do lar e a média de idade foram de 72,1 anos ± 8,6 anos. A média de tempo de internação foide 5,9 dias ± 8,8 dias, as doenças cardiovasculares foram as de maior ocorrência, tendo como desfecho clínico93,4% de altas hospitalares e 6,6% de óbitos e doenças hematológicas 100% de alta. Houve taxa significativa naassociação entre doenças e óbito por infecções (n=817; 60,0%). Foi estatisticamente significante a associação dasdoenças com o tipo de atendimento pelo SUS. Já a ocorrência de dor, doenças nefrourológicas, doenças ortopédicas,doenças hematológicas e ginecológicas e outras doenças apresentaram associação estatisticamente significativa com oatendimento particular ou convênio. A associação entre as doenças e o desfecho clínico demonstrou maior incidênciade óbito em pacientes acometidos por infecções. Foi estatisticamente significante a associação das doenças com o tipode atendimento destacando-se o atendimento pelo SUS

An Xpert screen to identify carbapenemases.

To prevent the spread of carbapenemases-producing Enterobacteriaceae (CPE) active surveillance, contact isolation and cohorting infected patients should be practiced. Rectal swabs for the Xpert MDRO-assay of 32 patients were included. 71.85% were positive for targets incorporated into the MDRO-assay; whereas 28% were phenotypically not CRE and Xpert negative (9.37% had different mechanism [blaOXA]). The assay identified 59.3%, 9.37% and 3.1% as blaNDM, blaNDM+VIM and blaVIM, respectively. The assay is a screening test that identifies CPE harbouring organism within an hour and can be installed at tertiary-care facilities to screen colonized patients.

Caracterização do perfil das emergências clínicas no pronto-atendimento de um hospital de ensino / Profile of clinical emergencies in the emergency department of a teaching hospital / Caracterización del perfil de emergencias clínicas en la guardia de un hospital escuela

O objetivo desta pesquisa foi investigar as características demográficas dos pacientes atendidos no pronto-atendimento da emergência de umHospital de Ensino, identificar as emergências clínicas predominantes e verificar o destino desses pacientes (alta, internação ou óbito). Trata-sede estudo transversal, retrospectivo, com análise quantitativa dos dados do prontuário eletrônico. A amostra foi constituída por 9.756 pacientesadultos com 18 anos ou mais, atendidos com diagnóstico médico de emergência clínica nos períodos de janeiro de 2009 a maio de 2010. Houvepredomínio do gênero feminino (56,33%), de etnia branca (86,95%), média de idade 48,74±7,8 anos. A faixa etária prevalente foi entre 18 e 29 anos,a maior parte dos pacientes (99,65%) declarou-se ativo e 60,23% casados. As doenças mais encontradas na neurologia foram: cefaleia (29,03%),acidente vascular encefálico (26,09%) e dorsalgia (10,25%). Na cardiologia as doenças mais comuns foram: dor precordial (38,98%), insuficiênciacardíaca (25,79%), hipertensão arterial (12,29%) e arritmia cardíaca (8,67%). O destino final dos pacientes atendidos na emergência clínica foi: altamédica (55,8%) e internação (43,26%)...

This study aimed to: investigate the demographic characteristics of patients seen in the emergency department of a teaching hospital; identify the mostcommon clinical emergencies; and identify the ultimate destination of these patients (medical discharge, hospitalization or death). This retrospective,cross-sectional, quantitative study. Data were collected from patients’ electronic medical records. Inclusion criteria were: adult patients 18 years or older,with a diagnosis of clinical emergency, seen in the period from January 2009 through May 2010. There was a predominance of: females (56.33%), of whiteethnicity (86.95%), and mean age 48.74 ± 7.8 years. The most prevalent age group was 18-29 years. Most of the patients (99.65%) declared themselves tobe active workers. 60.23% were married. The most frequent neurologic diseases found were: headache (29.03%); stroke (26.09%); and upper back pain(10.25%) and cardiological diseases were: precordial pain (38.98%), heart failure (25.79%), hypertension (12.29%) and cardiac arrhythmia (8.67%). Theultimate destinations of patients seen in the emergency department were: medical discharge (55.8%) and hospitalization (43.26%)...

Investigar las características demográficas de los pacientes atendidos en el servicio de urgencias de un hospital escuela; identificar las urgencias clínicas más comunes y verificar el destino final de los pacientes (alta médica, hospitalización o muerte). Estudio transversal y retrospectivo. Se realizó el análisis cuantitativo de datos extraídos de los registros médicos electrónicos. La muestra estaba formada por 9.756 pacientes. Los criterios deinclusión fueron: edad igual o superior a 18 años; tratarse de una urgencia clínica; en el período entre enero de 2009 y mayo de 2010. Predominaron elsexo femenino (56,33%), etnia blanca (86,95%), con media de edad de 48,74 ± 7,8 años. El grupo de edad más frecuente fue de 18-29 años. La mayoríade los pacientes (99,65%) declaró ser físicamente activo y 60,23% casado. Las enfermedades más frecuentes en neurología fueron: cefalea (29.035),accidente cerebrovascular (26,09%) y dorsalgia (10,25%) y en cardiologia dolor en el pecho (38,98%), insuficiencia cardíaca (25,79%), hipertensiónarterial (12,29%) y arritmia cardíaca (8,67%). El destino final de los pacientes atendidos varió entre alta médica (55,8%) y hospitalización (43,26%)...

Methicillin resistant Staphylococcus aureus (MRSA) in India Prevalence & susceptibility pattern.

Background & objectives: Methicillin resistant Staphylococcus aureus (MRSA) is endemic in India and is a dangerous pathogen for hospital acquired infections. This study was conducted in 15 Indian tertiary care centres during a two year period from January 2008 to December 2009 to determine the prevalence of MRSA and susceptibility pattern of S. aureus isolates in India. Methods: All S. aureus isolates obtained during the study period in the participating centres were included in the study. Each centre compiled their data in a predefined template which included data of the antimicrobial susceptibility pattern, location of the patient and specimen type. The data in the submitted templates were collated and analysed. Results: A total of 26310 isolates were included in the study. The overall prevalence of methicillin resistance during the study period was 41 per cent. Isolation rates for MRSA from outpatients, ward inpatients and ICU were 28, 42 and 43 per cent, respectively in 2008 and 27, 49 and 47 per cent, respectively in 2009. The majority of S. aureus isolates was obtained from patients with skin and soft tissue infections followed by those suffering from blood stream infections and respiratory infections. Susceptibility to ciprofloxacin was low in both MSSA (53%) and MRSA (21%). MSSA isolates showed a higher susceptibility to gentamicin, co-trimoxazole, erythromycin and clindamycin as compared to MRSA isolates. No isolate was found resistant to vancomycin or linezolid. Interpretation & conclusions: The study showed a high level of MRSA in our country. There is a need to study epidemiology of such infections. Robust antimicrobial stewardship and strengthened infection control measures are required to prevent spread and reduce emergence of resistance.

Prevalence and clinical course of Clostridium difficile infection in a tertiary-care hospital: a retrospective analysis.

The spectrum of Clostridium difficile-associated diarrhea (CDAD) is changing. Apart from antibiotic use, other risk factors such as use of proton pump inhibitors (PPI) and immunosuppressive agents, intensive care unit (ICU) stay and inflammatory bowel disease are being recognized. We retrospectively analyzed data on patients whose stool samples were tested for C. difficile toxin (CDT) by enzyme linked immunosorbent assay between June 2006 and May 2008. Demographic and clinical data, and risk factors (antibiotic use, underlying malignancy, chemotherapy, use of PPI, ICU stay) were noted. The details of treatment for CDAD, response, complication and follow up were recorded. Patients whose stool samples were CDT-positive were grouped as study subjects and those with negative stool samples were included in the control group. Of the 99 patients (mean age 46.7 years; 58 men) whose stool samples were tested during this period, 17 (17%) were positive for CDT. As compared with control subjects (n=82), study subjects were more likely to have fever, prolonged ICU stay, underlying malignancy, and exposure to immunosuppressive and chemotherapeutic agents. On multivariate analysis, exposure to immunosuppressive agents was the only risk factor associated with CDAD. Fifteen patients were treated with metronidazole and two with vancomycin. Two patients did not respond to metronidazole but responded to vancomycin. No patient developed any complication. The prevalence of C. difficile toxin in diarrheal stools sent for C. difficile toxin testing was 17%. Exposure to immunosuppressive agents was a risk factor for the infection. Metronidazole was effective in a majority of patients.

Comparison of Mycobacterium tuberculosis culture using liquid culture medium and Lowenstein Jensen medium in abdominal tuberculosis.

Background Traditionally, the Lowenstein Jensen (LJ) medium has been used for culturing Mycobacterium tuberculosis. In abdominal tuberculosis (TB), the reported yield from tissue culture is between 20% and 60%. Liquid cultures are reported to give a higher yield but there is little data available in abdominal TB. Aim To compare the yield of TB culture with BACTEC 460TB liquid medium and LJ medium for patients with suspected abdominal TB and determine cost effectiveness. Methods This prospective study was done in consecutive cases with clinical, radiological, endoscopic/surgical, and histological suspicion of abdominal TB. Tissue biopsies obtained at colonoscopy or surgery were processed and plated on LJ medium as well as the BACTEC 460TB system. NAP (ρ-nitro-α-acetylamino-β-hydroxy-propiophenone) differentiation was carried out to determine species. The cost of each method and cost per yield were calculated. Results Of the 29 cases, 22 cases (76%) were positive on BACTEC 460TB culture while 14 (48%) were positive on LJ medium giving a 64% increment in yield. However, the culture of one patient grew on LJ medium, where the BACTEC 460TB was negative. The additional cost of BACTEC 460TB is Rs. 460 and LJ is Rs. 40. Conclusions Samples from patients with abdominal TB should be processed on both liquid and LJ medium. For high yield, the use of a liquid culture medium system is essential.

Can cord formation in BACTEC MGIT 960 medium beused as a presumptive method for identification of M tuberculosis complex.

Background: Serpentine cord formation in BACTEC MGIT 960 medium was evaluated as a rapid method for the presumptive identification of M. tuberculosis complex (MTBC). Material & Methods: Total 2527 samples were processed for AFB culture using MGIT 960 TB system over a period of three months. AFB smears were prepared from 1000 MGIT tubes flagged positive by the MGIT instrument and stained by ZN method to examine presence or absence of serpentine cording. The cord formation was compared with PNBA [pnitro benzoic acid] test on MGIT system and all controversial cases were further evaluated by NAP [p-nitro-a-acetylaminophydroxypropiophenone] test on BACTEC 460 TB system. Results & Discussion: Of the 1000 culture positives, 904 (90.4%) were identified as mycobacteria, of which 869 (96%) showed cording by smear microscopy. One (0.1%) was identified as nocardia. In the remaining 95 (9.5%) cases, primary smear made from MGIT vial was negative. Of 869 cultures showing serpentine cord formation, 842 were confirmed as MTBC and 27 as NTM by PNBA assay on MGIT 960 TB system. The sensitivity, specificity, positive and negative predictive values are found to be 99.6%, 54%, 96% and 91% respectively. An average detection time for PNBA assay was found to be eight days whereas cording results were available on the same day of culture positivity. Conclusion: Though highly sensitive it is not very specific and hence cannot be the only test for presumptive diagnosis of MTBC.

Comparison of Phenotypic and Genotypic methods for Pyrazinamide susceptibility testing.

Objectives: To evaluate Pyrazinamide (PZA) susceptibility results obtained by phenotypic MGIT 960 TB system against enzymatic Pyrazinamidase assay and genotypic pncA gene sequencing. To find the prevalence of infections caused by M. bovis in PZA resistant M. tuberculosis complex isolates. Methods: 33 consecutive PZA resistant and 30 consecutive PZA susceptible isolates reported for PZA susceptibility testing by MGIT 960 TB system were included in this study. Presence of active pyrazinamidase enzyme was sought by using the Wayne assay. The pncA gene was amplified by PCR and then sequenced to screen mutations. All the PZA resistant isolates were further spoligotyped to identify M. bovis, if present. Results: Of 33 PZA resistant strains by MGIT 960, 31 were Wayne assay negative and two were positive. Of the 30 susceptible PZA strains six were Wayne assay negative reporting false resistance. PncA gene sequencing revealed that 32 of the 33 MGIT PZA resistant isolates had diverse nucleotide changes scattered throughout the pncA gene (one isolate did not show any mutation). Of the 30 phenotypically susceptible isolates, 21 were wild types whilst nine isolates showed the presence of a silent mutation C-T at codon 195. Fifteen mutations found in this study has not been described earlier. Not a single isolate of M. bovis was detected among PZA resistant M. tuberculosis complex isolates. Conclusion: MGIT 960 showed better concordance with sequencing results in comparison with Wayne assay. In present study, a high proportion (85%) of MDR-TB isolates from patients receiving anti-TB treatment were found to be resistant to PZA.

Acute enteritis associated with pneumococcal bacteremia.

We describe an elderly male who had a two day history of fever, abdominal pain and watery loose motions. Clinical examination was positive for abdominal right lower quadrant tenderness and moderate dehydration. Stool examination revealed inflammatory diarrhea. Considering the high prevalence of extended spectrum β-lactamases (ESBL) producing Gram-negative infections, he was treated with Piperacillin/Tazobactam. Surprisingly, his blood culture which was taken on admission returned positive for Streptococcus pneumoniae after two days, which was coincident with resolution of fever and diarrhea. This patient had no other clinically apparent source of Pneumococcal infection and we believe that he had Pneumococcal enteritis with bacteremia. There are very few reported cases of isolated Pneumococcal enteritis in the literature. Therefore, we report this unusual form of Streptococcus pneumoniae infection both because of its rarity and its potentially life-threatening but still curable nature. ©

Nocardiosis in a patient with common variable immunodeficiency.

We report a case of nocardiosis in a 42, years male with common variable immunodeficiency syndrome (CVID). He presented with arthritis, subcutaneous abscess and pleural effusion. Diagnosis of CVID was made during this presentation. Serum IgG, IgA and IgM levels were markedly decreased. Nocardia asteroides was cultured from pleural fluid. He was successfully treated with intravenous immunoglobulin and cotrimoxazole.

Purpura fulminans due to Enterococcus faecalis.

We report a case of a 73 year old man who developed purpura fulminans due to Enterococcus faecalis sepsis. The patient was treated successfully with oral linezolid. Early diagnosis of the microbial etiology of purpura fulminans is important. If Enterococcus faecalis is found as the causal organism, appropriate antimicrobial therapy may be used.

Comparing serology, antigenemia assay and polymerase chain reaction for the diagnosis of cytomegalovirus infection in renal transplant patients.

BACKGROUND: Cytomegalovirus (CMV) disease is responsible for significant morbidity and mortality following renal transplantation. Currently serology is the only method widely available in our country. Newer methods like early CMV pp65 antigenemia assay and CMV DNA amplification can diagnose CMV disease in its very early period. AIM: The aim of our study was to compare serologic method with antigenemia assay and CMV DNA amplification to diagnose CMV. METHODS: Seventy-three renal transplant recipients (from 7 centres) with clinical suspicion of CMV disease were studied prospectively. The diagnosis of CMV infection was suspected on the basis of fever and leucopenia. RESULT AND DISCUSSION: Three tests were done in all 73 patients and in 22 healthy subjects (control group). The sensitivity and specificity of serological test (CMV IgM) was 72.97 and 62.06%; of antigenemia assay was 89.18 and 100% and of PCR was 100 and 72.41%. CONCLUSION: Antigenemia assay is a sensitive and specific test for early and rapid diagnosis of CMV infection. Qualitative PCR is a sensitive marker but has low specificity.