Complex Lemierre syndrome with multisystemic abscesses.

We present here the challenging case of severe Lemierre syndrome in a healthy woman in her late twenties, whose clinical presentation was characterised by lung abscesses and disseminated systemic abscesses in the brain, the abdomen and the soft-tissues, as a likely consequence of a patent foramen ovale. Blood cultures were positive for Fusobacterium necrophorum and a right lingual vein thrombosis was detected at a late stage when the patient developed a septic shock. Initial antimicrobial therapy with metronidazole and ceftriaxone was modified to meropenem due to progressive worsening. The patient underwent laparoscopy and neurosurgical drainage of a cerebral abscess. She spent many days in the intensive care unit and recovered fully after 6 weeks on meropenem therapy. Although considered rare, the incidence of Lemierre syndrome, a potentially life-threatening condition, is increasing. The clinician should promptly recognise and treat it while being aware of its potential atypical presentations.

Gamma-Delta T-Cell Phenotype and Function in DAA-Treated HIV-HCV Co-Infected and HCV-Mono-Infected Subjects.

HIV-HCV co-infected subjects are at risk of liver fibrosis which may be linked to immune imbalances. Direct-acting antivirals (DAAs) represent the mainstay of HCV treatment in co-infected individuals, yet their effects on immune cell populations playing a role in fibrogenesis is unknown. We assessed γδ T-cell phenotype and function, Treg and Th17 frequencies, as well as γ-globulins and B-cell activation in 47 HIV-HCV co-infected and 35 HCV mono-infected individuals prior to and following DAA treatment (SVR12). Γδ T-cell activation decreased in both groups yet persisted at higher levels in the HIV-HCV co-infected subjects. No differences were registered in terms of γδT-cell function. Of note, the Vδ2/Th17 ratio, inversely linked to liver damage, increased significantly in the two groups upon treatment, yet a negative correlation between the Vδ2/Th17 ratio and liver function enzymes was found in the co-infected subjects alone. B-cell activation and γ-globulin levels decreased in both settings, yet B-cell activation remained higher in the HIV-HCV co-infected individuals. In HIV-HCV co-infected and HCV mono-infected participants, the effect of DAA was limited to γδ T- and B-cell activation as well as γ-globulin concentrations and the Vδ2/Th17 ratio, with no changes in γδ T-cell function and Treg frequencies. Importantly, γδ T- and B-cell activation remained at higher levels in the co-infected individuals than in those with HCV mono-infection alone. The persistence of such alterations within these cell subsets may be associated with the risk of hepatic and extrahepatic complications.

Antibiotic Therapy for Difficult-to-Treat Infections in Lung Transplant Recipients: A Practical Approach.

Lung transplant recipients are at higher risk to develop infectious diseases due to multi-drug resistant pathogens, which often chronically colonize the respiratory tract before transplantation. The emergence of these difficult-to-treat infections is a therapeutic challenge, and it may represent a contraindication to lung transplantation. New antibiotic options are currently available, but data on their efficacy and safety in the transplant population are limited, and clinical evidence for choosing the most appropriate antibiotic therapy is often lacking. In this review, we provide a summary of the best evidence available in terms of choice of antibiotic and duration of therapy for MDR/XDR P. aeruginosa, Burkholderia cepacia complex, Mycobacterium abscessus complex and Nocardia spp. infections in lung transplant candidates and recipients.

Central nervous system infections in solid organ transplant recipients: Results from the Swiss Transplant Cohort Study.

OBJECTIVES: To describe the epidemiology and clinical presentation of central nervous system (CNS) infections in solid organ transplant (SOT) recipients in the current era of transplantation. METHODS: Patients from the Swiss Transplant Cohort Study (STCS) transplanted between 2008 and 2018 were included with a median follow-up of 3.8 years. Epidemiological, microbiological, and clinical data were extracted from the STCS database and patients' medical records. We calculated incidence rates and 90-day survival of transplant recipients with CNS infection. RESULTS: Among 4762 patients, 42 episodes of CNS infection in 41 (0.8%) SOT recipients were identified, with an overall incidence rate of 2.06 per 1000 patient-years. Incidence of CNS infections was similar across all types of transplantations. Time to CNS infection onset ranged from 0.6 to 97 months after transplant. There were 22/42 (52.4%) cases of viral infections, 11/42 (26.2%) of fungal infections, 5/42 (11.9%) of bacterial infections and 4/42 (9.5%) of probable viral/bacterial etiology. Clinical presentation was meningitis/encephalitis in 25 cases (59.5%) and brain-space occupying lesions in 17 cases (40.5%). Twenty-three cases (60.5%) were considered opportunistic infections. Diagnosis were achieved mainly by brain biopsy/necropsy (15/42, 36%) or by cerebrospinal fluid analysis (20/42, 48%). Up to 40% of cases (17/42) had concurrent extra-neurological disease localizations. Overall, 90-day mortality rate was 29.0% (73.0% for fungal, 14.0% for viral and 11.0% for bacterial and probable infections, p<0.0001). CONCLUSIONS: CNS infections were rare in the STCS, with viral meningoencephalitis being the most common disease. Fungal infections were associated with a high mortality.

Epidemiology and outcomes of medically attended and microbiologically confirmed bacterial foodborne infections in solid organ transplant recipients.

Food-safety measures are recommended to solid organ transplant (SOT) recipients. However, the burden of foodborne infections in SOT recipients has not been established. We describe the epidemiology and outcomes of bacterial foodborne infections in a nationwide cohort including 4405 SOT recipients in Switzerland between 2008 and 2018. Participants were prospectively followed for a median of 4.2 years with systematic collection of data on infections, and patient and graft-related outcomes. We identified 151 episodes of microbiologically confirmed bacterial foodborne infections occurring in median 1.6 years (IQR 0.58-3.40) after transplantation (131 [88%] Campylobacter spp. and 15 [10%] non-typhoidal Salmonella). The cumulative incidence of bacterial foodborne infections was 4% (95% CI 3.4-4.8). Standardized incidence rates were 7.4 (95% CI 6.2-8.7) and 4.6 (95% CI 2.6-7.5) for Campylobacter and Salmonella infections, respectively. Invasive infection was more common with Salmonella (33.3% [5/15]) compared to Campylobacter (3.2% [4/125]; p = .001). Hospital and ICU admission rates were 47.7% (69/145) and 4.1% (6/145), respectively. A composite endpoint of acute rejection, graft loss, or death occurred within 30 days in 3.3% (5/151) of cases. In conclusion, in our cohort bacterial foodborne infections were late post-transplant infections and were associated with significant morbidity, supporting the need for implementation of food-safety recommendations.

Understanding rare infections post-lung transplantation.

Introduction: Lung transplant recipients are at the highest risk of infectious complications among all solid-organ transplant (SOT) recipients. In the current era, many standardized protocols in terms of diagnostic algorithms, prophylaxis, and therapeutic strategies have improved the management of the most common infectious complications. Conversely, diagnosis of rare infections can be particularly challenging and this can delay appropriate treatment.Areas covered: This article will review the epidemiology, clinical presentation, diagnostic and therapeutic management of certain rarely reported viral, fungal, bacterial and parasitic infections in lung transplant recipients.Expert opinion: Once the most frequent infections are excluded, clinical suspicion combined with molecular diagnostic methods such as targeted and broad-spectrum PCRs can allow diagnosis of a rare infection. A multidisciplinary team, including transplant pulmonologists, transplant infectious diseases specialists, microbiologists and pathologists is essential for prompt diagnosis and optimal therapeutic management.

Impact of HCV eradication with direct-acting antiviral agents on serum gamma globulin levels in HCV and HCV/HIV coinfected patients.

BACKGROUND: chronic viral infections by both HCV and HIV may lead to polyclonal activation of B cells resulting in hypergammaglobulinemia. This study retrospectively analyzed the effect of HCV eradication with interferon-free direct-acting antiviral agents (DAAs) on the gamma globulin levels in HCV-infected patients with or without HIV coinfection to identify factors potentially associated with gamma globulins decrease. METHODS: The charts of patients treated with DAAs for HCV chronic infection between January 2015-June 2019 were retrospectively reviewed. Gamma globulin levels before treatment and 12 weeks after the end of anti-HCV therapy were evaluated along with liver tests, liver fibrosis stage by elastography, SVR achievement, HIV-coinfection. Multivariate analyses were carried out to assess the factors and the potential confounders related to the changes in gamma globulin levels. RESULTS: A significant decrease of gamma globulin concentration was found in both cirrhotic and non-cirrhotic HCV-infected patients after treatment (from mean ± SD of 1.5 ± 0.44 g/dL to 1.31 ± 0.37 g/dL; p = 0.0001). Adjusted linear regression analyses of serum gamma globulin changes from baseline to SVR12 showed a positive significant association with pre-treatment gamma-globulin levels (ß-coefficient -0.23; p = 0.0001), Metavir fibrosis score (ß-coefficient -0.74; p = 0.008), ALT values and baseline HCV-RNA levels > 800,000. No difference was found between HIV-infected and HIV-uninfected patients. CONCLUSIONS: Our study confirms previous preliminary observation of the decrease of serum gamma globulins after HCV eradication either achieved with interferon-based therapy or with DAAs, suggesting a leading role of the virus on the activation of B cell compartment and gamma globulins production.

Overlooked cases of HIV infection: An Italian tale of missed diagnostic opportunities.

BACKGROUND: Late diagnoses are still a cause of increased HIV-related morbidity and mortality despite the availability of highly effective treatments. The aim of this study was to identify indicator conditions (ICs) in late presenters with HIV infection (LPs) that may represent missed opportunities of undertaking earlier HIV testing. METHODS: The medical records of LPs referred to a specialist clinic in Milan, Italy, between 2011 and 2017 were reviewed to assess the frequency of ICs during the five years preceding diagnosis. Logistic regression analysis was used to investigate the factors associated with missed opportunities of making an earlier diagnosis. RESULTS: The analysis considered 203 LPs (60.6% of the patients newly diagnosed as having HIV infection during the study period). Most had had ≥1 medical encounter in the five years before diagnosis, and 54 (26.6%) had been diagnosed as having ≥1 IC without undergoing HIV testing. The most frequent ICs were herpes zoster (19.8%), constitutional symptoms (17.4%) and lympho/thrombocytopenia (12.8%), and the missed opportunities for testing occurred in the settings of primary care (44.9%), specialist medical (38.2%) or surgical services (11.3%), and emergency departments (5.6%). Twenty-five (53.2%) of the 47 subjects with a non AIDS-defining IC had AIDS at the time of the diagnosis of HIV infection. Subjects aged >60 years were at increased risk of missed diagnostic opportunities (aOR 4.80, p = 0.008). CONCLUSION: Implementing IC-guided HIV testing in non-specialist settings is an essential means of reducing late diagnoses of HIV infection even in the case of older subjects.

Real-life food-safety behavior and incidence of foodborne infections in solid organ transplant recipients.

Food-safety measures are recommended in solid organ transplant (SOT) recipients. However, the actual adherence of patients in a real-life setting and the impact on the incidence of foodborne infections remain largely unexplored. We performed a survey among SOT recipients followed at our institution, aiming to evaluate their food-safety behavior. We assessed the incidence of microbiologically proven foodborne infections by chart review. One hundred ninety-seven SOT recipients (kidney = 117, lung = 35, liver = 29, and heart = 16) participated in the survey. Overall, 17.7% of the participants observed all food-safety recommendations (22.0% avoided food at risk of contamination while 67.9% applied hygiene recommendations). Patients within the first year after transplantation (odds ratio [OR] 5.42; P = .001) and females (OR 4.67; P = .001) followed food-safety recommendations more closely. Although the majority of SOT recipients felt concerned and actively sought information on food safety (68%-70%), only 27% were able to recognize all risks of foodborne infection in hypothetical scenarios. Incidence of proven foodborne infections was 17.9% (95% confidence interval 9.9%-30.9%) 5 years after transplantation. Importantly, foodborne infections occurred exclusively among patients not following food-safety recommendations. In summary, most SOT recipients eat foods that make them at risk of foodborne infections. Our results indicate that there is room for improvement in patient education, particularly later after transplantation, and reinforce current food-safety recommendations.

Is there a role for procalcitonin determination in avoiding unnecessary exposure to antibiotics in a non-intensive care setting?

The use of procalcitonin (PCT) as a tool to assist clinicians in using antibiotics in intensive care patients has been postulated. Here we evaluate the efficacy of procalcitonin determination in helping clinicians in the decision to start or discontinue an antibiotic treatment in patients admitted to infectious disease wards. A retrospective observational single centre study was conducted in two infectious disease wards. Descriptive and inferential statistical analysis was carried out and receiver operating characteristic curves and area under the curve (AUC) were used to assess the accuracy of PCT and C-reactive protein (CRP) in separating patients undergoing antibiotic treatment or otherwise. In all, 164 patients were analysed of whom 99 (60.4%) were not on antibiotic treatment at the time of PCT determination, whereas 65 (39.6%) took antibiotics. Regarding the accuracy of PCT and CRP in determining a subsequent antibiotic prescription in patients without an ongoing antibiotic treatment, no statistically significant difference between the two markers was detected [AUC, 0.75; confidence interval (CI) 95%: 0.66-0.84; vs 0.69; CI 95%: 0.59-0.79 for PCT and CRP, respectively; p=0.32]. Conversely, in patients with an ongoing antibiotic treatment a statistically significant difference between PCT and CRP AUC in their ability to determine an antibiotic interruption was observed [0.77 (CI 95%: 0.65-0.89) vs 0.59 (CI 95%: 0.45-0.73) (p=0.03)]. PCT determination appeared to be more helpful than CRP in determining discontinuation of an antibiotic treatment in non-intensive care patients. However, PCT should supplement and not supplant a careful clinical evaluation.

Burden of Exposure to Potential Interactions Between Antiretroviral and Non-Antiretroviral Medications in a Population of HIV-Positive Patients Aged 50 Years or Older.

BACKGROUND: As HIV-infected patients aged 50 years or older are at increased risk of comorbidities and multidrug treatments, we examined their exposure to the potential drug-drug interactions (PDDIs) of antiretroviral (ARV) and other medications. METHODS: This cross-sectional study involved the patients aged 50 years or older receiving ARV and non-ARV medications at our clinic. PDDIs were identified using the University of Liverpool HIV Drug Interaction Checker. Logistic regression models were used to assess risk factors for PDDIs. The American Geriatrics Society Beers Criteria were used to identify potentially inappropriate medications (PIMs). RESULTS: A total of 395 (53.9%) of 744 patients showed ≥1 PDDI: 47.4% ≥ 1 amber-PDDI (comedications requiring appropriate management) and 5.6% ≥ 1 red-PDDI (contraindicated comedications). A higher risk of PDDIs was associated with the use of ≥5 medications (P < 0.001), of antiosteoporotics (P < 0.001), calcium channel blockers (P < 0.001), anti-benign prostatic hypertrophy agents (P < 0.001), hypnotics/sedatives (P = 0.022), and anticoagulants (P = 0.006). A higher risk of red-PDDIs was associated with the use of antacids (P < 0.001), anti-benign prostatic hypertrophy agents (P < 0.001) and antipsychotics (P = 0.023). The use of nucleoside reverse transcriptase inhibitor + nonnucleoside reverse transcriptase inhibitor and nucleoside reverse transcriptase inhibitor + integrase strand transfer inhibitor rather than protease inhibitor-based regimens was associated with a reduced risk of PDDIs (P < 0.001). Overall, 119 (16.0%) patients were receiving PIMs (mainly hypnotics/sedatives) and 49 (41.2%) of them had PDDIs able to increase the blood levels of these medications. CONCLUSIONS: Older patients with HIV are highly exposed to PDDIs between ARVs and comedications. The knowledge of their complete medication regimens and the screening for PDDIs and PIMs is therefore crucial to prevent drug-related adverse outcomes in this population.

Changes in the incidence of severe thrombocytopenia and its predisposing conditions in HIV-infected patients since the introduction of highly active antiretroviral therapy.

BACKGROUND: Severe thrombocytopenia (TCP, platelets <50 × 109/L) is relatively frequent during HIV infection and is associated with bleeding risk and disease progression. We investigated the changes in the incidence of severe TCP and its predisposing conditions in a cohort of HIV-positive subjects. METHODS: The incidence and predictors of platelet counts <50 × 109/L were investigated in all patients enrolled at our institution between 1985 and 2012. Three different periods were considered on the basis of the available antiretroviral regimens: P1 (1985-1989), P2 (1990-1996), and P3 (1997-2012). Incidence rates were assessed using Poisson regression models and the predictors by means of Cox regression. RESULTS: The study involved 5137 patients with platelet counts >50 × 109/L at enrollment. Severe TCP occurred in 597 subjects, and its incidence decreased over time. The incidence decreased in patients with opportunistic diseases and malignancies but increased in patients with chronic liver disease; TCP unrelated to any cause other than HIV infection remained stable. Multivariate analysis showed that injected drug use, a diagnosis of AIDS, low CD4⁺ cell counts, increased serum alanine aminotransferase levels, and an earlier year of enrollment were predictors of an increased risk of severe TCP, whereas the use of highly active antiretroviral therapy (HAART) was associated with a reduced risk. CONCLUSIONS: A considerable reduction in the incidence of severe TCP after the introduction of HAART was found, probably because of its ability to limit bone marrow damage induced by uncontrolled HIV replication and opportunistic infections. On the contrary, HAART may have a reduced impact on TCP related to chronic liver disease.