Microbiological Distribution, Antimicrobial Susceptibility and Risk Factors of Polymicrobial Infections in Diabetic Foot.

BACKGROUND: Diabetic foot infection (DFI) leads to poor prognosis and polymicrobial infections are usually the main cause. The study is to explore the microbiological distribution, antimicrobial drug susceptibility, and risk factors of polymicrobial infections in hospitalized patients with DFI. METHODS: This retrospective study included 160 patients with DFI in Wagner's grades 2, 3, and 4. Deep necrotic tissue was used to acquire specimens for microbiological culture. VITEK-2 system and MALDI-TOF mass spectrometry were used to identify the bacterial isolates. The Kirby Bauer method was used for drug susceptibility tests. RESULTS: A total of 202 pathogens were isolated. The proportion of gram-negative bacilli (GNB, 62.4%, 126 of 202) was higher than that of gram-positive cocci (GPC, 37.6%, 76 of 202). The most prevalent GPC was Staphylococcus aureus in every Wagner grade, while the most common GNB varied in different Wagner grades. Linezolid was the most effective antibiotic for GPC in different Wagner grades. Imipenem was the most effective antibiotic for GNB in Wagner grade 2. Amikacin was the most effective antibiotic for GNB in Wagner grades 3 and 4. Polymicrobial infections existed only in Wagner grades 3 and 4 and increased the risk of amputation (p < 0.01). History of antibiotics, duration of diabetic foot, CRP, and lower extremity arterial disease were the independent risk factors of polymicrobial infections (p < 0.05). CONCLUSIONS: Clinicians should adjust the antibiotic as needed based on the results of drug susceptibility and clinical treatment effect among different Wagner grades. Particular attention should be given to the treatment of polymicrobial infections.

HIV-TB Coinfection: Current Therapeutic Approaches and Drug Interactions.

The co-occurrence of human immunodeficiency virus (HIV) and tuberculosis (TB) infection poses a significant global health challenge. Treatment of HIV and TB co-infection often necessitates combination therapy involving antiretroviral therapy (ART) for HIV and anti-TB medications, which introduces the potential for drug-drug interactions (DDIs). These interactions can significantly impact treatment outcomes, the efficacy of treatment, safety, and overall patient well-being. This review aims to provide a comprehensive analysis of the DDIs between anti-HIV and anti-TB drugs as well as potential adverse effects resulting from the concomitant use of these medications. Furthermore, such findings may be used to develop personalized therapeutic strategies, dose adjustments, or alternative drug choices to minimize the risk of adverse outcomes and ensure the effective management of HIV and TB co-infection.

No gender differences in the 24-month course of non-invasive liver fibrosis markers after DAA therapy in HCV-mono and HCV/HIV-coinfected patients.

Untreated HCV mono and HCV/HIV coinfected women have lower degrees of liver fibrosis (LF) compared to men. Direct acting antiviral (DAA) therapy attains viral eradication in > 90% of patients with progressive LF decline in parallel. Gender-related differences in LF regression in the long term assessed by non-invasive liver fibrosis markers (NILFM) in HCV mono and HCV/HIV coinfected after DAA treatment have not been explored so far. 374 HCV-infected adult patients, 214 of them HCV/HIV coinfected, were followed-up for 24 months after starting DAA therapy. LF was assessed by NILFM: transient elastometry (TE) and several biochemical indexes (APRI, Forns, FIB-4). Men had significantly more advanced LF at baseline than women assessed by NILFM. No LF differences at baseline in age, HIV coinfection course (CD4, HIV viral load), and HCV features (HCV viral load, genotype) were detected. No significant gender differences in LF decline after comparing 24-month and baseline LF values were observed. LF changes after DAA therapy were similar in HCV mono and HCV/HIV coinfected patients and in both sexes. Gender did not influence the course of LF decline after DAA assessed by NILFM: TE (P = 0.8), APRI (P = 0.9), Forns (P = 0.4) and FIB-4 (P = 0.7) by multivariate analysis. No gender differences in the 24 month LF decline after DAA with independence of having HCV mono or HCV/HIV coinfection were found.

Leishmania and HIV co-infection: first naturally Leishmania strain presenting decreased susceptibility to miltefosine, recovered from a patient in Portugal.

BACKGROUND: In Europe, up to 70% of visceral leishmaniasis (VL) cases occurring in adults living with HIV. People living with HIV with VL co-infection often display persistent parasitemia, requiring chronic intermittent anti-Leishmania therapies. Consequently, frequent VL relapses and higher mortality rates are common in these individuals. As such, it is of paramount importance to understand the reasons for parasite persistence to improve infection management. METHODS: To outline possible causes for treatment failure in the context of HIV-VL, we followed a person living with HIV-VL co-infection for nine years in a 12-month period. We characterized: HIV-related clinicopathological alterations (CD4+ T counts and viremia) and Leishmania-specific seroreactivity, parasitemia, quantification of pro-inflammatory cytokines upon stimulation and studied a Leishmania clinical isolate recovered during this period. RESULTS: The subject presented controlled viremia and low CD4+ counts. The subject remained PCR positive for Leishmania and also seropositive. The cellular response to parasite antigens was erratic. The isolate was identified as the first Leishmania infantum case with evidence of decreased miltefosine susceptibility in Portugal. CONCLUSION: Treatment failure is a multifactorial process driven by host and parasite determinants. Still, the real-time determination of drug susceptibility profiles in clinical isolates is an unexplored resource in the monitoring of VL.

Hepatitis B virus and cytomegalovirus coinfection in an older patient: a case report.

Cytomegalovirus (CMV) infection involving the skin is relatively rare. We herein report a case involving a man in his late 70s with positive hepatitis B surface antigen who presented with multiform skin lesions, including a papuloid rash, papular urticaria, and purpura. The patient had taken no antiviral drugs for nearly 13 years but had recently developed severe liver injury. Laboratory examination revealed positive CMV immunoglobulin M, CMV polymerase chain reaction result of 1.09 × 102 copies/mL, and a slightly decreased CD4+ cell count; however, the CD8+ T-cell count was within the normal range. A skin biopsy was performed in the region of the papular eruption on the left inner thigh, and the pathologic findings were consistent with CMV infection. After admission, the patient began a combination of antiviral therapy for hepatitis B virus and CMV. After 3 weeks of treatment, the patient was discharged with skin lesions, and his liver function recovered.

Impact of mixed-infection rate of clarithromycin-susceptible and clarithromycin-resistant Helicobacter pylori strains on the success rate of clarithromycin-based eradication treatment.

BACKGROUND: Clarithromycin (CAM) resistance is a major contributor to the failure to eradicate Helicobacter pylori (H. pylori). The mixed-infection ratio of CAM-susceptible and CAM-resistant H. pylori strains differs among individuals. Pyrosequencing analysis can be used to quantify gene mutations at position each 2142 and 2143 of the H. pylori 23S rRNA gene in intragastric fluid samples. Herein, we aimed to clarify the impact of the rate of mixed infection with CAM-susceptible and CAM-resistant H. pylori strains on the success rate of CAM-containing eradication therapy. MATERIALS AND METHODS: Sixty-four H. pylori-positive participants who received CAM-based eradication therapy, also comprising vonoprazan and amoxicillin, were enrolled in this prospective cohort study. Biopsy and intragastric fluid samples were collected during esophagogastroduodenoscopy. H. pylori culture and CAM-susceptibility tests were performed on the biopsy samples, and real-time PCR and pyrosequencing analyses were performed on the intragastric fluid samples. The mutation rates and eradication success rates were compared. RESULTS: The overall CAM-based eradication success rate was 84% (54/64): 62% (13/21) for CAM-resistant strains, and 95% (39/41) for CAM-sensitive strains. When the mutation rate of the 23S rRNA gene was 20% or lower for both positions (2142 and 2143), the eradication success rate was 90% or more. However, when the mutation rate was 20% or higher, the eradication success rate was lower (60%). CONCLUSIONS: The mutation rate of the CAM-resistance gene was related to the success of eradication therapy, as determined via pyrosequencing analysis.

Staphopain mediated virulence and antibiotic resistance alteration in co-infection of Staphylococcus aureus and Pseudomonas aeruginosa: an animal model.

Polymicrobial communities lead to worsen the wound infections, due to mixed biofilms, increased antibiotic resistance, and altered virulence production. Promising approaches, including enzymes, may overcome the complicated condition of polymicrobial infections. Therefore, this study aimed to investigate Staphopain A-mediated virulence and resistance alteration in an animal model of Staphylococcus aureus and Pseudomonas aeruginosa co-infection. S. aureus and P. aeruginosa were co-cultured on the L-929 cell line and wound infection in an animal model. Then, recombinant staphopain A was purified and used to treat mono- and co-infections. Following the treatment, changes in virulence factors and resistance were investigated through phenotypic methods and RT-PCR. Staphopain A resulted in a notable reduction in the viability of S. aureus and P. aeruginosa. The biofilm formed in the wound infection in both animal model and cell culture was disrupted remarkably. Moreover, the biofilm-encoding genes, quorum sensing regulating genes, and virulence factors (hemolysin and pyocyanin) controlled by QS were down-regulated in both microorganisms. Furthermore, the resistance to vancomycin and doripenem decreased following treatment with staphopain A. According to this study, staphopain A might promote wound healing and cure co-infection. It seems to be a promising agent to combine with antibiotics to overcome hard-to-cure infections.

The course of COVID-19 in a multiple sclerosis: a case report.

The authors present the case of a prolonged course of COVID 19 disease in a 37-year-old patient with multiple sclerosis on anti-CD20 monoclonal antibodies immunotherapy. This publication presents a clinical case of the course of COVID-19 disease in a multiple sclerosis patient receiving ublituximab therapy. The use of disease-modifying anti-CD20 monoclonal antibody therapy was associated with a protracted wave-like course of COVID-19 with the addition of a bacterial infection. This publication illustrates the key mechanisms and approaches to the treatment of such a cohort of patients. The use of highly effective multiple sclerosis treatment methods may be associated with an increase in the incidence of COVID-19 and worsening of its course. Multiple sclerosis patients receiving anti-CD20 therapy are at particular risk of a wave-like course of COVID-19, caused by immunosuppression, creates a basis for bacterial and fungal coinfection.

The Rapidly Changing Patterns in Bacterial Co-Infections Reveal Peaks in Limited Gram Negatives during COVID-19 and Their Sharp Drop Post-Vaccination, Implying Potential Evolution of Co-Protection during Vaccine-Virus-Bacterial Interplay.

SARS-CoV-2 has caused the most devastating pandemic of all time in recent human history. However, there is a serious paucity of high-quality data on aggravating factors and mechanisms of co-infection. This study aimed to identify the trending patterns of bacterial co-infections and types and associated outcomes in three phases of the pandemic. Using quality hospital data, we have investigated the SARS-CoV-2 fatality rates, profiles, and types of bacterial co-infections before, during, and after COVID-19 vaccination. Out of 389 isolates used in different aspects, 298 were examined before and during the pandemic (n = 149 before, n = 149 during). In this group, death rates were 32% during compared to only 7.4% before the pandemic with significant association (p-value = 0.000000075). However, the death rate was 34% in co-infected (n = 170) compared to non-co-infected patients (n = 128), indicating a highly significant value (p-value = 0.00000000000088). However, analysis of patients without other serious respiratory problems (n = 28) indicated that among the remaining 270 patients, death occurred in 30% of co-infected patients (n = 150) and only 0.8% of non-co-infected (n = 120) with a high significant p-value = 0.00000000076. The trending patterns of co-infections before, during, and after vaccination showed a significant decline in Staphylococcus aureus with concomitant peaks in Gram negatives n = 149 before/n = 149 during, including Klebsiella pneumonian = 11/49 before/during, E. coli n = 10/24, A. baumannii n = 8/25, Ps. aeruginosa n = 5/16, and S. aureus 13/1. Nevertheless, in the post-vaccination phase (n = 91), gender-specific co-infections were examined for potential differences in susceptibility. Methicillin-resistant S. aureus dominated both genders followed by E. coli in males and females, with the latter gender showing higher rates of isolations in both species. Klebsiella pneumoniae declined to third place in male patients. The drastic decline in K. pneumoniae and Gram negatives post-vaccination strongly implied a potential co-protection in vaccines. Future analysis would gain more insights into molecular mimicry.

Respiratory virus coinfections during the COVID-19 pandemic: epidemiologic analysis and clinical outcomes from the Phase 2/3 molnupiravir trial (MOVe-OUT).

This exploratory post hoc analysis assessed the incidence of respiratory viral coinfections and their impact on clinical outcomes in non-hospitalized adults with mild-to-moderate coronavirus disease-2019 (COVID-19) treated with molnupiravir versus placebo for 5 days in the Phase 2/3 MOVe-OUT trial (NCT04575597), which took place in October 2020 to January 2021 (Phase 2, n = 302) and May 2021 to October 2021 (Phase 3, n = 1,433). Among 1,735 total randomized participants, 1,674 had a baseline respiratory pathogen panel (NxTAG Respiratory Pathogen Panel for the Luminex MAGPIX instrument) performed and 69 (4.1%) were coinfected with at least one additional respiratory viral pathogen. Human rhinovirus/enterovirus (39/69, 56.5%) was the most common coinfection detected at baseline. In the modified intention-to-treat population, two participants with coinfecting respiratory RNA viruses were hospitalized and received respiratory interventions through Day 29, and none died; one participant in the molnupiravir group was coinfected with human rhinovirus/enterovirus, and one participant in the placebo group was coinfected with human metapneumovirus. Hospitalization or death occurred in 6.2% and 9.0% of non-coinfected participants in the molnupiravir versus placebo group, respectively, and over 90% did not require respiratory interventions. Most coinfecting respiratory RNA viruses detected at baseline were not detected at the end of therapy in both the molnupiravir and placebo groups. In summary, participants coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and another respiratory RNA virus were not more likely to be hospitalized or die, or require respiratory interventions, compared to participants who were not coinfected with another respiratory RNA virus at baseline in both groups. IMPORTANCE: Respiratory viral coinfections are known to occur with coronavirus disease-2019 (COVID-19). In a cohort of non-hospitalized adults with mild-to-moderate COVID-19 treated with molnupiravir versus placebo in the MOVe-OUT trial during October 2020 to October 2021, 4.1% of participants had a documented viral coinfection; human rhinovirus/enterovirus was the most common pathogen detected with the NxTAG Respiratory Pathogen Panel assay. Participants who had a coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and another respiratory RNA virus were not more likely to have worse clinical outcomes compared to those participants without a viral coinfection, and many coinfecting respiratory RNA viruses were no longer detected at the end of the 5-day treatment period in both groups.

Mortality and associated factors among people living with HIV admitted at a tertiary-care hospital in Uganda: a cross-sectional study.

BACKGROUND: Hospital admission outcomes for people living with HIV (PLHIV) in resource-limited settings are understudied. We describe in-hospital mortality and associated clinical-demographic factors among PLHIV admitted at a tertiary-level public hospital in Uganda. METHODS: We performed a cross-sectional analysis of routinely collected data for PLHIV admitted at Kiruddu National Referral Hospital between March 2020 and March 2023. We estimated the proportion of PLHIV who had died during hospitalization and performed logistic regression modelling to identify predictors of mortality. RESULTS: Of the 5,827 hospitalized PLHIV, the median age was 39 years (interquartile range [IQR] 31-49) and 3,293 (56.51%) were female. The median CD4 + cell count was 109 cells/µL (IQR 25-343). At admission, 3,710 (63.67%) were active on antiretroviral therapy (ART); 1,144 (19.63%) had interrupted ART > 3 months and 973 (16.70%) were ART naïve. In-hospital mortality was 26% (1,524) with a median time-to-death of 3 days (IQR 1-7). Factors associated with mortality (with adjusted odds ratios) included ART interruption, 1.33, 95% confidence intervals (CI) 1.13-1.57, p 0.001; CD4 + counts ≤ 200 cells/µL 1.59, 95%CI 1.33-1.91, p < 0.001; undocumented CD4 + cell count status 2.08, 95%CI 1.73-2.50, p < 0.001; impaired function status 7.35, 95%CI 6.42-8.41, p < 0.001; COVID-19 1.70, 95%CI 1.22-2.37, p 0.002; liver disease 1.77, 95%CI 1.36-2.30, p < 0.001; co-infections 1.53, 95%CI 1.32-1.78, p < 0.001; home address > 20 km from hospital 1.23, 95%CI 1.04-1.46, p 0.014; hospital readmission 0.7, 95%CI 0.56-0.88, p 0.002; chronic lung disease 0.62, 95%CI 0.41-0.92, p 0.019; and neurologic disease 0.46, 95%CI 0.32-0.68, p < 0.001. CONCLUSION: One in four admitted PLHIV die during hospitalization. Identification of risk factors (such as ART interruption, function impairment, low/undocumented CD4 + cell count), early diagnosis and treatment of co-infections and liver disease could improve outcomes.

Mismatch Rate of Empirical Antimicrobial Treatment in Fracture-Related Infections.

OBJECTIVES: To evaluate the current standard of care regarding empirical antimicrobial therapy in fracture-related infections (FRIs). DESIGN: Retrospective cohort study. SETTING: Level I Trauma Center. PATIENT SELECTION CRITERIA: Adult patients treated for FRI with surgical debridement and empirical antibiotics between September 1, 2014, and August 31, 2022. Patients were excluded if less than 5 tissue samples for culture were taken, culture results were negative, or there was an antibiotic-free window of less than 3 days before debridement. OUTCOME MEASURES AND COMPARISONS: FRI microbial etiology, antimicrobial resistance patterns (standardized antimicrobial panels were tested for each pathogen), the mismatch rate between empirical antimicrobial therapy and antibiotic resistance of causative microorganism(s), and mismatching risk factors. RESULTS: In total, 75 patients were included [79% (59/75) men, mean age 51 years]. The most prevalent microorganisms were Staphylococcus aureus (52%, 39/75) and Staphylococcus epidermidis (41%, 31/75). The most frequently used empirical antibiotic was clindamycin (59%, 44/75), followed by combinations of gram-positive and gram-negative covering antibiotics (15%, 11/75). The overall mismatch rate was 51% (38/75) [95% confidence interval (CI), 0.39-0.62] and did not differ between extremities [upper: 31% (4/13) (95% CI, 0.09-0.61), lower: 55% (33/60) (95% CI, 0.42-0.68, P = 0.11)]. Mismatching empirical therapy occurred mostly in infections caused by S. epidermidis and gram-negative bacteria. Combination therapy of vancomycin with ceftazidime produced the lowest theoretical mismatch rate (8%, 6/71). Polymicrobial infections were an independent risk factor for mismatching (OR: 8.38, 95% CI, 2.53-27.75, P < 0.001). CONCLUSIONS: In patients with FRI, a mismatching of empirical antibiotic therapy occurred in half of patients, mainly due to lack of coverage for S. epidermidis , gram-negative bacteria, and polymicrobial infections. Empirical therapy with vancomycin and ceftazidime produced the lowest theoretical mismatch rates. This study showed the need for the consideration of gram-negative coverage in addition to standard broad gram-positive coverage. Future studies should investigate the effect of the proposed empirical therapy on long-term outcomes. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The Effect of Immunoglobulin G on the Humoral Immunity in Patients with Tuberculosis/HIV Coinfection.

Previously, an increase in clinical effectiveness of the antituberculosis treatment (ATT) and antiretroviral therapy (ART) in case of additional immunoglobulin G (IgG) administration in patients with multidrug-resistant tuberculosis (MDR-TB)/HIV coinfection was reported. The aim of this study was to investigate the impact of IgG administration in addition to the standard second-line ATT and ART on the humoral immunity status in patients with MDR-TB/HIV coinfection immune deficiency. The study involved 52 patients living with HIV with MDR-TB coinfection and CD4+ lymphocyte cell count below 50 cells/µCL. Patients in the control group and intervention group received the second-line ATT and ART; in addition, patients in the intervention group received IgG intravenously. The humoral immunity status was evaluated by measurement of IgA, IgE, IgG, and IgM in plasma. The standard ATT and ART resulted in a two-step change in humoral immunity: IgM, IgG, IgA, and IgE levels gradually increased to a maximal level at the 5-month mark and started to gradually decrease after the 8-month mark. Addition of IgG to the standard therapy resulted in a steeper decrease in the immunoglobulin level in serum, especially IgG, compared with standard therapy alone, allowing for an earlier initiation of ART in patients in the intervention group.

The co-infection of pulmonary hydatid cyst, lophomoniasis and tuberculosis in a patient with resistant respiratory symptoms; a case report study.

BACKGROUND: Lophomonas blattarum is a rare protozoan that causes opportunistic infections, and the co-infection of lophomonas with tuberculosis and human hydatidosis is a serious public problem in the co-endemic areas of developing countries. CASE REPORT: We presented a 58-year-old female with fever, losing weight, and cough with whitish-yellow sputum that started one month ago. Increasing inflammatory markers and hypereosinophilia in laboratory tests, and a cavity with thick, regular walls and undulating air-fluid levels measuring 43 × 30, evident in the upper segment of the right lower lobe (RLL), along with consolidation and the ground glass opacity of the upper segment and posterior basal of the RLL is apparent in CT scan were reported. Then, a bronchoscopy was requested, and the BAL specimen reported a negative fungal and bacterial infection in the samples. Several live and oval flagellated lophomonas protozoa, hydatid cyst protoscoleces (the larval forms of the parasites), and M. tuberculosis were observed in microscopic evaluation. The patient was treated with metronidazole, oral albendazole, and a combination of TB regimen. CONCLUSION: Physicians should always consider the possibility of co-infections of lophomonas with tuberculosis and human hydatidosis and investigate patients with risk factors such as immunodeficiency conditions or treated with immunosuppressive medications.

The healing effect of Pseudomonas Quinolone Signal (PQS) with co-infection of Staphylococcus aureus and Pseudomonas aeruginosa: A preclinical animal co-infection model.

BACKGROUND: Because of the rise in antibiotic resistance and the control of pathogenicity, polymicrobial bacterial biofilms exacerbate wound infections. Since bacterial quorum sensing (QS) signals can dysregulate biofilm development, they are interesting therapeutic treatments. In this study, Pseudomonas Quinolone Signal (PQS) was used to treat an animal model of a wound that had both Staphylococcus aureus and Pseudomonas aeruginosa co-infection. METHODS: S. aureus and P. aeruginosa mono- and co-infection models were developed in vitro on the L-929 cell line and in an animal model of wound infection. Moreover, PQS was extracted and purified using liquid chromatography. Then, the mono- and co-infection models were treated by PQS in vitro and in vivo. RT-PCR analysis was used to look into changes in biofilm, QS, tissue regeneration, and apoptosis genes after the treatment. RESULTS: PQS significantly disrupted established biofilm up to 90% in both in vitro and in vivo models. Moreover, a 93% reduction in the viability of S. aureus and P. aeruginosa was detected during the 10 days of treatment in comparison to control groups. In addition, the biofilm-encoding and QS-regulating genes were down-regulated to 75% in both microorganisms. Also, fewer epithelial cells died when treated with PQS compared to control groups in both mono- and co-infection groups. CONCLUSION: According to this study, PQS may facilitate wound healing by stimulating the immune system and reducing apoptosis. It seems to be a potential medication to use in conjunction with antibiotics to treat infections that are difficult to treat.

Co-infection of Nocardia and Aspergillus fumigatus in a immunosuppressed patient: Case report.

BACKGROUND: Nocardia and Aspergillus fumigatus are opportunistic pathogenic fungus that has a major impact on the mortality of rheumatoid arthritis patients. Opportunistic infections in immunocompromised patients present diagnostic challenges. Nocardia and A fumigatus are both easily overlooked because of their rarity, leading to delayed diagnosis and treatment. CASE PRESENTATION: We report an infection caused by steroid use in a patient with rheumatoid arthritis. A 76-year-old man with a history of rheumatoid arthritis was admitted to our hospital because of cough, expectoration and fever for 10 days. The patient had low immune function, granulocytopenia, diffuse infiltration could be seen on chest computed tomography, and BAL fluid galactomannan level of 1.3 S/CO. The microbiological findings reflect a possible co-infection with Nocardia and A fumigatus. Voriconazole was used to treat pulmonary aspergillosis, ceftriaxone and Trimethoprim-Sulfamethoxazole were used to treat Nocardia. After timely targeted medication administration, the patient was discharged with a good prognosis. CONCLUSION: Co-infection is more common in immunosuppressed patients and warrants attention in clinical practice. Early diagnosis and treatment can help patients with Co-infection of Nocardia and A fumigatus achieve better prognosis.

Hepatitis B virus coinfection in patients treated for chronic hepatitis C: clinical characteristics, risk of reactivation with long-term follow-up, and effectiveness of antiviral therapy.

INTRODUCTION: Hepatitis B virus (HBV) and hepatitis C virus (HCV) share a similar transmission route, which increases coinfection odds and worsens clinical outcomes. OBJECTIVES: Our aim was to investigate coinfected patients undergoing HCV treatment with direct-acting antivirals (DAAs) to understand their characteristics, risk of HBV reactivation, and effectiveness of the therapy. PATIENTS AND METHODS: Our study comprehensively analyzed 1118 patients with chronic HCV infection, divided into 3 subgroups based on their HBV status. RESULTS: We documented that 0.7% of the analyzed population was positive for hepatitis B virus surface antigen (HBsAg), while 14.3% had evidence of a past HBV infection. The patients without HBV coinfection were less burdened with comorbidities, and were mostly treatment-naive, while the individuals suffering from coinfection were younger and more likely to have a history of a previous therapy. Infection with HCV genotype 3 was more common among the HBsAg-positive patients than in the other studied groups. Response to DAA therapy was comparable between the groups, and most patients completed the course of treatment as planned. Only 3 cases of HBV reactivation were observed, all of which achieved sustained virologic response after DAA therapy. Two were women on immunosuppressants with antihepatitis B core positive antibodies, and the third patient was an HBsAgpositive man. These patients remained in long-term follow-up. CONCLUSIONS: Neither the presence of HBV markers nor HBV reactivation during DAA treatment reduced effectiveness of the therapy. Our findings are important for future recommendations and guidelines on managing HBV/HCV coinfection.

Factors associated with immunological non-response after ART initiation: a retrospective observational cohort study.

BACKGROUND: Among people living with HIV (PLHIV) on antiretroviral therapy (ART), the mortality of immunological non-responders (INRs) is higher than that of immunological responders (IRs). However, factors associated with immunological non-response following ART are not well documented. METHODS: We obtained data for HIV patients from the National Free Antiretroviral Treatment Program database in China. Patients were grouped into IRs (CD4 cell count ≥ 350 cells/µl after 24 months' treatment), immunological incomplete responders (ICRs) (200-350 cells/µl) and INRs (< 200 cells/µl). Multivariable logistic regression was used to assess factors associated with immunological non-response. RESULTS: A total of 3900 PLHIV were included, among whom 2309 (59.2%) were IRs, 1206 (30.9%) ICRs and 385 (9.9%) INRs. In multivariable analysis, immunological non-response was associated with being male (2.07, 1.39-3.09), older age [40-49 years (vs. 18-29 years): 2.05, 1.29-3.25; 50-59 years: 4.04, 2.33-7.00; ≥ 60 years: 5.51, 2.84-10.67], HBV co-infection (1.63, 1.14-2.34), HCV co-infection (2.01, 1.01-4.02), lower CD4 + T cell count [50-200 cells/µl (vs. 200-350 cells/µl): 40.20, 16.83-96.01; < 50 cells/µl: 215.67, 85.62-543.26] and lower CD4/CD8 ratio (2.93, 1.98-4.34) at baseline. Compared with patients treated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens, those receiving protease inhibitors (PIs) based regimens were less likely to be INRs (0.47, 0.26-0.82). CONCLUSIONS: We found a sizable immunological non-response rate among HIV-infected patients. Being male, older age, coinfection with HBV and HCV, lower CD4 + T cell count and lower CD4/CD8 ratio are risk factors of immunological non-response, whereas PIs-based regimens is a protective factor.

Bacterial infections in patients with COVID-19: the impact of procalcitonin testing on antibiotics prescription in the real world.

BACKGROUND: Bacterial infections are not prevalent among patients hospitalized with COVID-19, while unnecessary prescription of antibiotics was commonly observed. This study aimed to determine the impact of procalcitonin testing on antibiotics prescription in the real-world setting. METHODS: We performed a territory-wide retrospective cohort study involving all laboratory-confirmed patients hospitalized in public hospitals in Hong Kong in 2020 with COVID-19. We determined the prevalence of bacterial co-infections (documented infections within 72 h of admission) and secondary bacterial infections (infections after 72 h of admission) and antibiotics consumption, and the correlation between procalcitonin testing and antibiotics prescription. RESULTS: The cohort included 8666 patients, with mean age 45.3 ± 19.9 years, 48.5% male, and comorbidities in 26.9%. Among 2688 patients with bacterial cultures performed, 147 (5.5%) had bacterial co-infections, and 222 (8.3%) had secondary bacterial infections. Antibiotics were prescribed for 2773 (32.0%) patients during the hospital admission. Procalcitonin tests were performed for 2543 (29.3%) patients. More patients with procalcitonin testing received antibiotics (65.9% vs. 17.9%, p < 0.001). Procalcitonin testing was associated with 5-fold increased risk of antibiotics prescription after adjusting for confounding variables. At hospital level, procalcitonin testing correlated with antibiotics prescription. Patients with procalcitonin level < 0.5 ng/mL had a lower probability of antibiotics initiation and shorter duration of antibiotics therapy. CONCLUSIONS: Procalcitonin testing was not associated with lower prescription of antibiotics. Patients with low procalcitonin level had lower antibiotics exposure, supporting the use of procalcitonin to exclude bacterial infections aiding early stopping of antibiotics among patients hospitalized with COVID-19.