Etiology, clinical characteristics, and outcome of infective endocarditis: 10-year experience from a tertiary care center in Pakistan.

This study was conducted to assess the clinical characteristics, causative agents, complications, and outcomes of infective endocarditis (IE) among patients presenting to our tertiary care center over the last decade. This retrospective cohort study included all adult patients admitted to the Aga Khan University Hospital with the diagnosis of IE over a ten-year period from 2010 to 2020.  Outcomes variables included complications during hospitalization, surgical intervention, mortality, and length of stay. We identified a total of 305 cases out of which 176 (58%) were males and 129 (42%) were females. The mean age of the patients was 46.9±18.8 years. 95 (31%) had prosthetic valves in place. Staphylococcus aureus was isolated in 54 (39%) patients followed by coagulase-negative Staphylococcus in 23 (17%). Echocardiography revealed vegetations and abscesses in 236 (77%) and 4 (1%) patients, respectively. The most common valvular complication was mitral valve regurgitation found in 26 (9%) patients, followed by tricuspid valve regurgitation in 13 (4%) patients and aortic valve regurgitation in 11 (3%) patients. Furthermore, 81 (27%) patients suffered from heart failure and 66 (22%) from a stroke during hospitalization. The mean hospital length of stay was 10.4 ± 10.6 days. 64 (21%) patients required surgical repair and the overall mortality rate was 25%. Prosthetic valve endocarditis (OR = 3.74, 95% CI = 2.15-6.50, p<0.001), chronic kidney disease (OR = 2.51, 95% CI = 1.15-5.47, p=0.036), previous stroke (OR = 2.42, 95% CI = 1.18-4.96, p=0.026), and ischemic heart disease (OR = 3.04, 95% CI = 1.50-6.16, p=0.003) were significantly associated with an increased risk of mortality. In conclusion, our study provided valuable data on the clinical characteristics and outcomes of patients with IE in a developing country. S. aureus was the most common causative agent. Heart failure and stroke were the most common complications. The presence of prosthetic valves, history of chronic kidney disease, ischemic heart disease and previous stroke were associated with a significantly increased risk of mortality. Surgical management was not associated with improved outcomes.

Diagnostic Value of 16S Ribosomal RNA Gene Polymerase Chain Reaction/Sanger Sequencing in Clinical Practice.

BACKGROUND: Accurate microbiologic diagnosis is important for appropriate management of infectious diseases. Sequencing-based molecular diagnostics are increasingly used for precision diagnosis of infections. However, their clinical utility is unclear. METHODS: We conducted a retrospective analysis of specimens that underwent 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR) followed by Sanger sequencing at our institution from April 2017 through March 2019. RESULTS: A total of 566 specimens obtained from 460 patients were studied. Patients were considered clinically infected or noninfected based on final diagnosis and management. In 17% of patients, 16S rRNA PCR/sequencing was positive and in 5% of patients, this test led to an impact on clinical care. In comparison, bacterial cultures were positive in 21% of patients. Specimens with a positive Gram stain had 12 times greater odds of having a positive molecular result than those with a negative Gram stain (95% confidence interval for odds ratio, 5.2-31.4). Overall, PCR positivity was higher in cardiovascular specimens (37%) obtained from clinically infected patients, with bacterial cultures being more likely to be positive for musculoskeletal specimens (P < .001). 16S rRNA PCR/sequencing identified a probable pathogen in 10% culture-negative specimens. CONCLUSION: 16S rRNA PCR/sequencing can play a role in the diagnostic evaluation of patients with culture-negative infections, especially those with cardiovascular infections.

Staphylococcus simulans bloodstream infection following CIED extraction.

A 78-year-old man with an implantable cardioverter-defibrillator (ICD) presented with chills and malaise. His history was significant for heart failure with reduced ejection fraction and complete heart block. He had undergone permanent pacemaker placement that was later upgraded to an ICD 5 years before his presentation. Physical examination revealed an open wound with surrounding erythema overlying the device site. Blood cultures obtained on admission were negative. Transesophageal echocardiogram did not show valve or lead vegetations. He underwent a prolonged extraction procedure. Postoperatively, he developed septic shock and cultures from the device, and repeat peripheral blood cultures grew Staphylococcus simulans and Staphylococcus epidermidis He was treated with intravenous vancomycin but had refractory hypotension, leading to multiorgan failure. He later expired after being transitioned to comfort care. The patient may have acquired S. simulans by feeding cows on a nearby farm, and the prolonged extraction procedure may have precipitated the bacteraemia.

COVID-19 pandemic: from origins to outcomes. A comprehensive review of viral pathogenesis, clinical manifestations, diagnostic evaluation, and management.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative pathogen for the COVID-19, first emerged in Wuhan, China, in December 2019 and by March 2020, it was declared a pandemic. COVID-19 pandemic has overburdened healthcare systems in most countries and has led to massive economic losses. SARS-CoV-2 transmission typically occurs by respiratory droplets. The average incubation period is 6.4 days and presenting symptoms typically include fever, cough, dyspnea, myalgia or fatigue. While the majority of patients tend to have a mild illness, a minority of patients develop severe hypoxia requiring hospitalization and mechanical ventilation. Management is mostly supportive. However, several direct anti-viral agents, and immunomodulatory therapy with steroids and various cytokine blockers seem promising in early results. However, an effective vaccine has been established, which will help curb the pandemic.

Lawsonella clevelandensis: an emerging cause of vascular graft infection.

Lawsonella clevelandensis, an emerging pathogen, was first described in 2016, and has been implicated in abdominal, breast and spinal abscesses in a limited number of cases. Being a fastidious organism, it is primarily identified with molecular methods. With the incorporation of broad-range PCR testing in clinical diagnostics, L. clevelandensis has been increasingly reported in the literature. We describe a case of a 65-year-old man who presented with bilateral psoas abscesses secondary to aorto-bi-iliac vascular graft infection with L. clevelandensis identified using 16S rRNA/PCR sequencing. The patient underwent surgical resection and replacement of infected graft, followed by 6 weeks of intravenous antibiotic therapy and then chronic suppression with doxycycline and cefadroxil. He was infection-free at last follow-up.

Positron emission tomography objective parameters for assessment of left ventricular assist device infection using 18F-FDG PET/CT.

Left ventricular assist device (LVAD) is a life-saving therapy, but it poses a substantial infection risk. Current evaluation of LVAD infection with 18F-FDG PET/CT is predominately subjective. We present qualitative and semi-quantitative 18F-FDG PET/CT parameters for early detection of LVAD infection and site localization. We retrospectively reviewed all 25 LVAD patients at our institution who had undergone 18F-FDG PET/CT imaging between 2014 and 2018. LVADs were subdivided into five assessed regions: driveline exit site, subcutaneous driveline, LVAD pump, LVAD inflow, and LVAD outflow cannulae. Ultimate diagnosis of LVAD infection was determined by a multidisciplinary primary care team. Qualitative and semi-quantitative analysis of PET/CT data were performed, including calculation of the standardized uptake value maximum, mean, and peak (SUVmax, SUVmean, and SUVpeak, respectively), as well as metabolic tumor volume (MTV), and total lesion glycolysis (TLG). A total of 14 patients presented with symptoms of infection, and LVAD infection was ultimately diagnosed in 19 of the 25 cases. All cases were correctly identified on 18F-FDG PET/CT with no false positive and no false negative cases, corresponding to a sensitivity and specificity of 100%. The mean SUVmax range at noninfected sites was 2.5-3.4, and the range was 5.7-8.1 at infected sites, resulting in a significant difference (P < 0.01) at all LVAD regions. 18F-FDG PET/CT is a useful adjunctive tool for assessment of LVAD infection and infection localization, which is crucial for clinical management. A cut-off SUVmax 5 is recommended to help diagnose LVAD infection.

Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, previously named 2019-nCov), a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th, 2020. Severe manifestations of COVID-19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage. DISCUSSION: We reviewed published literature between January 1st, 2000 and June 30th, 2020, excluding articles focusing on pediatric or obstetric population, with a focus on virus-host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome (CRS). COVID-19 illness encompasses three main phases. In phase 1, SARS-CoV-2 binds with angiotensin converting enzyme (ACE)2 receptor on alveolar macrophages and epithelial cells, triggering toll like receptor (TLR) mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙB) signaling. It effectively blunts an early (IFN) response allowing unchecked viral replication. Phase 2 is characterized by hypoxia and innate immunity mediated pneumocyte damage as well as capillary leak. Some patients further progress to phase 3 characterized by cytokine storm with worsening respiratory symptoms, persistent fever, and hemodynamic instability. Important cytokines involved in this phase are interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α. This is typically followed by a recovery phase with production of antibodies against the virus. We summarize published data regarding virus-host interactions, key immunological mechanisms responsible for virus-associated CRS, and potential opportunities for therapeutic interventions. CONCLUSION: Evidence regarding SARS-CoV-2 epidemiology and pathogenesis is rapidly evolving. A better understanding of the pathophysiology and immune system dysregulation associated with CRS and acute respiratory distress syndrome in severe COVID-19 is imperative to identify novel drug targets and other therapeutic interventions.

Reduced bacterial adhesion with parylene coating: Potential implications for Micra transcatheter pacemakers.

INTRODUCTION: Infections of cardiac implantable electronic devices remain a prevalent health concern necessitating the advent of novel preventative strategies. Based on the observation that bacterial infections of the Micra transcatheter pacemaker device are extremely rare, we examine the effect of parylene coating on bacterial adhesion and growth. METHODS: Bacterial growth was compared on polyurethane coated, bare, or parylene coated titanium surfaces. Eight test samples per bacterial species and material combination were incubated with Staphylococcus Aureus or Pseudomonas aeruginosa for 24 hours and then assayed for bacterial growth. The surface contact angle was also characterized by measuring the angle between the tangent to the surface of a liquid droplet made with the surface of the solid sample. RESULTS: The mean bacterial colony counts were significantly reduced for both parylene coated titanium versus bare samples (3.69 ± 0.27 and 4.80 ± 0.48 log[CFU/mL] respectively for S. aureus [P < .001] and 5.51 ± 0.27 and 6.08 ± 0.11 log[CFU/mL] respectively for P. aeruginosa [P < .001]), and for parylene coated titanium versus polyurethane samples (4.27 ± 0.42 and 5.40 ± 0.49 log[CFU/mL] respectively for S. aureus [P < .001] and 4.23 ± 0.42 and 4.84 ± 0.32 log[CFU/mL] respectively for P. aeruginosa [P = .006]). Parylene coated titanium samples had a higher contact angle compared with bare titanium, but lower compared with polyurethane (mean contact angle 87.5 ± 3.1 degrees parylene, 73.3 ± 3.7 degrees titanium [P < .001 vs parylene], and 94.8 ± 3.7 degrees polyurethane [P = .002 vs parylene]). CONCLUSIONS: Parylene coating significantly reduced the ability of bacteria to grow in colony count assays suggesting that this could contribute to the reduction of bacterial infections of Micra transcatheter pacemakers.

Disseminated Cryptococcus neoformans infection in a left ventricular assist device recipient.

A 51-year-old man with a medical history of coronary artery disease and dyslipidaemia presented with acute myocardial infarction resulting in cardiogenic shock, necessitating intra-aortic balloon pump placement and extracorporeal membrane oxygenation (ECMO). His hospital course was complicated by several infectious complications including ECMO circuit Pseudomonas aeruginosa bloodstream infection and presumed infected right atrial thrombus. He subsequently underwent urgent left ventricular assist device placement and had a prolonged hospital stay. On day 100 of admission, he developed acute hypoxic respiratory distress with new pulmonary infiltrates. Sputum cultures grew Cryptococcus neoformans Blood culture also grew C. neoformans after 96 hours of incubation and cryptococcal serum antigen was elevated at 1:20. Cerebrospinal fluid studies from a lumbar puncture were normal. He was treated with 2 weeks of combination antifungal therapy followed by life-long fluconazole suppression.

Infection Management.

Cardiovascular implantable electronic devices (CIEDs) and the indications for their use have significantly risen over the past decades to include patients who are older with more medical comorbidities. Predictably, the rates of CIED infection have increased substantially. CIED infection is associated with high morbidity, mortality, and financial costs. This article discusses the appropriate management of CIED infections, which is imperative to limit the problems associated with infection.

Secondary bacterial peritonitis and pelvic abscess due to Clostridium difficile.

A 70-year-old man with a history of hepatic cirrhosis presented with abdominal discomfort and distention. Physical examination revealed abdominal distention, positive fluid wave and abdominal tenderness. Due to concerns for spontaneous bacterial peritonitis (SBP), paracentesis was performed. Fluid analysis revealed 5371 total nucleated cells with 48% neutrophils. Ceftriaxone was then initiated for the treatment of SBP. Bacterial cultures of the fluid, however, grew Clostridium difficile Therefore, metronidazole was added. An abdominal ultrasound revealed a pelvic fluid collection that was suspicious for an abscess on an abdominal CT scan. The patient underwent CT-guided drain placement into the pelvic fluid collection. The fluid aspirate was consistent with an abscess. However, cultures were negative in the setting of ongoing antibiotic therapy. The patient was treated with a 10-day course of ceftriaxone and metronidazole and was discharged home with outpatient follow-up.

Clinical presentation of CIED infection following initial implant versus reoperation for generator change or lead addition.

Objective: To explore differences in clinical manifestations and outcomes in those patients who develop infection after undergoing initial implantation versus reoperation. Methods: We compared cases of cardiac implantable electronic device (CIED) infection based on initial implantation versus reoperation from 11 centres. Results: There were 432 patients with CIED infection, 178 occurring after initial device placement and 254 after repeat reoperation. No differences were seen in age, sex or device type. Those with infection after initial implant had a higher Charlson Comorbidity Score (median 3 (IQR 2-6) vs 2 (IQR 1-4), p<0.001), shorter time since last procedure (median 8.9 months (IQR 0.9-33.3) vs 19.5 months (IQR 1.1-62.9), p<0.0001) and fewer leads (2.0±0.6vs 2.5±0.9, p<0.001). Pocket infections were more likely to occur after a reoperation (70.1%vs48.9%, p<0.001) and coagulase negative staphylococci (CoNS) was the most frequently isolated organism in this group (p=0.029). In contrast, initial implant infections were more likely to present with higher white cell count (10.5±5.1 g/dL vs 9.5±5.4 g/dL, p=0.025), metastatic foci of infection (16.9%vs8.7%, p=0.016) and sepsis (30.9%vs19.3%, p=0.006). There were no differences in in-hospital (7.9%vs5.2%, p=0.31) or 6-month mortality (21.9%vs14.0%, p=0.056). Conclusions: CIED infections after initial device implant occur earlier, more aggressively, and often due to Staphylococcus aureus. In contrast, CIED infections after reoperation occur later, are due to CoNS, and have more indolent manifestations with primary localisation to the pocket.

Attempted salvage of infected cardiovascular implantable electronic devices: Are there clinical factors that predict success?

BACKGROUND: Published guidelines mandate complete device removal in cases of cardiovascular implantable electronic device (CIED) infection. Clinical predictors of successful salvage of infected CIEDs have not been defined. METHODS: Data from the Multicenter Electrophysiologic Device Infection Collaboration, a prospective, observational, multinational cohort study of CIED infection, were used to investigate whether clinical predictors of successful salvage of infected devices could be identified. RESULTS: Of 433 adult patients with CIED infections, 306 (71%) underwent immediate device explantation. Medical management with device retention and antimicrobial therapy was initially attempted in 127 patients (29%). "Early failure" of attempted salvage occurred in 74 patients (58%) who subsequently underwent device explantation during the index hospitalization. The remaining 53 patients (42%) in the attempted salvage group retained their CIED. Twenty-six (49%) had resolution of CIED infection (successful salvage group) whereas 27 patients (51%) experienced "late" salvage failure. Upon comparing the salvage failure group, early and late (N = 101), to the group experiencing successful salvage of an infected CIED (N = 26), no clinical or laboratory predictors of successful salvage were identified. However, by univariate analysis, coagulase-negative staphylococci as infecting pathogens (P = 0.0439) and the presence of a lead vegetation (P = 0.024) were associated with overall failed salvage. CONCLUSIONS: In patients with definite CIED infections, clinical and laboratory variables cannot predict successful device salvage. Until new data are forthcoming, device explantation should remain a mandatory and early management intervention in patients with CIED infection in keeping with existing expert guidelines unless medical contraindications exist or patients refuse device removal.

Cranial neuropathy and severe pain due to early disseminated Borrelia burgdorferi infection.

A 61-year-old man presented to the emergency department in the summer with a right seventh cranial nerve lower motor neuron palsy and worsening paraesthesias for 6 weeks. He had debilitating pain at the scalp and spine. Prior work up was unrevealing. The patient resided in the upper Midwest region of the USA and worked outdoors, optimising the landscape for white tailed deer. Repeat cerebrospinal fluid testing revealed a lymphocytic pleocytosis and positive IgM Lyme serology. Brain MRI demonstrated enhancement of multiple cranial nerves bilaterally. He was diagnosed with early Lyme neuroborreliosis and treated with 28 days of intravenous ceftriaxone. While the painful meningoradiculitis, also known as Bannwarth syndrome, is more commonly seen in Europe, facial palsy is more frequently encountered in the USA. Clinical manifestations of neuroborreliosis are important to recognise as the classic presentation varies by geography and on occasion repeat serological testing may be necessary.

Herpes Zoster During Immunosuppressive Therapy For Autoimmune Diseases.

BACKGROUND: Patients on immunosuppressive therapy are at a greater risk for herpes zoster reactivation and are more likely to have adverse outcomes. Propylactic antivrials and vaccinations may potentially prevent these complications. METHODS: Medical literature addressing the clinical course and therapy of herpes zoster in patients receiving immunosuppressive therapy for autoimmune disorders, and the roles of anti-viral prophylaxis and vaccination was reviewed. Research databases including PubMed, Ovid, Medline, Google Scholar and Cochrane were utilized. RESULTS: Acyclovir and its derivatives are most commonly used in this setting for treatment and reduction of post-zoster complications. Foscarnet may be used for acyclovir-resistant strains. At both conventional and ultralow doses, acyclovir has proven effective when used as prophylaxis, reducing the incidence of zoster and its complications in immunosuppressed patients. Additionally, ultra-low doses are associated with significantly reduced side effects. The zoster vaccine, Zostavax, a live-attenuated vaccine has shown promising results in several clinical trials. However, live-attenuated vaccines should be cautiously used in immunosuppressed patients. For patients who require immunosuppressive therapy, vaccination 2-3 months prior to therapy may be appropriate. CONCLUSIONS: Prophylactic antiviral therapy and vaccination help significantly reduce morbidity and mortality from zoster reactivation in patients receiving immunosuppressive therapy.

Isolated cerebral mucormycosis caused by Rhizomucor pusillus.

A 61-year-old man with relapsing chronic lymphocytic leukaemia, status post allogeneic stem cell transplant and multiple chemotherapy regimens presented to the emergency room after suffering a grand mal seizure. His evaluation revealed a 1.5-2 cm ring-enhancing left temporal lobe brain lesion on the CT scan. This brain lesion was resected and the histopathology revealed an invasive fungal organism resembling mucormycosis. Amplification and sequencing of the 28S ribosomal RNA gene identified the organism as Rhizomucor pusillus The patient was treated with liposomal amphotericin B 5 mg/kg every 24 hours for 4 weeks, and then was transitioned to oral posaconazole. Serial brain imaging at 1 and 3 months, while on therapy, showed significant improvement.

Postsurgical mediastinal aspergilloma masquerading as malignancy.

A 70-year-old man with non-ischaemic dilated cardiomyopathy presented with symptoms of fatigue, chills and unintentional weight loss over the past 2 months. Initial evaluation revealed anaemia, peripheral leucocytosis and elevated inflammatory markers. Results of an oesophagogastroduodenoscopy, colonoscopy, blood bacterial and fungal cultures and bone marrow biopsy were negative. An 18F-FDG positron-emission tomography-CT demonstrated an indeterminate, intensely FDG-avid 5 cm × 2 cm × 5.6 cm × 6.7 cm mass centred within the junction of the superior vena cava and right atrium, suggestive of probable malignancy versus an inflammatory thrombus. After multidisciplinary consideration, patient underwent a diagnostic minithoracotomy and a thick fibrotic mediastinal mass was visualised and evacuated. The encapsulated mass contained thick, white creamy liquid that appeared to be purulent/necrotic material. The biopsies of the capsule wall on frozen section demonstrated fungal elements consistent with Aspergillosis species. Fungal culture confirmed diagnosis of Aspergillus fumigatus.

Helcococcus kunzii prosthetic valve endocarditis secondary to lower extremity cellulitis.

An 88-year-old man with history of bioprosthetic aortic valve replacement was hospitalised with fever, chills, malaise and right lower extremity cellulitis. Laboratory investigations revealed leucocytosis and blood cultures grew Helcococcus kunzii Although transoesophageal echocardiography was negative for endocarditis, the patient was treated with 4 week of intravenous ceftriaxone. However, he was readmitted 6 weeks later with symptoms of fever, chills and hypoxia in setting of recurrent H. kunzii bacteraemia. A repeat transoesophageal echocardiogram revealed a mobile mass on bioprosthetic aortic valve, severe perivalvular insufficiency with pseudoaneurysm formation, and severe native mitral and tricuspid valve regurgitation. Cardiothoracic surgery was consulted and the patient underwent replacement of aortic valve and aortic root, and tricuspid and mitral valve repairs. Histological examination of excised bioprosthetic aortic valve revealed active endocarditis with cocci identified on silver stain. Patient was successfully treated with 4-week course of intravenous ceftriaxone and was doing well at 2-year follow-up.