ABSTRACT
Is there an increased incidence of bacteraemia among COVID-19 patients requiring critical care admission who have received IL-6 inhibitors? Introduction: Interleukin-6 (IL-6) inhibitors have been shown to reduce mortality in hospitalised COVID-19 patients. There is, however, concern that induced immunosuppression may increase the risk of secondary nosocomial infection. Objective(s): Our primary aim was to determine if there was increased incidence of bacteraemia in COVID-19 patients requiring critical care admission who had received IL-6 inhibitors compared to those who had not. Method(s): A retrospective review of all COVID-19 admissions to two critical care units in Liverpool from 4th March 2020 to 31st October 2021. Patients were divided into those who received an IL-6 inhibitor (sarilumab or tociluzimab) and those who did not. Hospital antimicrobial policy was to administer a five day prophylactic course of co-amoxiclav and clarithromycin for patients with severe COVID-19 during the study period. Blood culture results from 14 days before admission to critical care and 90 days after admission were included. The blood culture results comprised cultures taken in both critical care and on the wards. Data were linked and analysed using Stata V15.1 (StataCorp, Stata Statistical Software: Release 15, College Station, Texas, USA). Result(s): 894 patients were included in the study. 134 patients had at least one positive blood culture result. The most commonly identified pathogens were Coliforms (23/134, 17.2%), Enterobacter (22/134, 16.4%) and Escherichia coli (16/134, 11.9%). Of patients administered an IL-6 antagonist, 16.8% (114/565) developed a positive blood culture compared to 11.6% (20/172) who did not, p=0.096. We did not observe an increased frequency of antimicrobial resistant culture in the IL-6 administered group 22.8% (26/114) vs. 20.0% (4/20) in this cohort, p=0.781. Data have not been adjusted for demographic and clinical factors in this preliminary analysis. Conclusion(s): We observed a trend toward increased frequency of blood culture positivity in patients administered an IL-6 antagonist within this COVID-19 positive cohort but this was not statistically significant. Further analysis is required to adjust for relevant demographic and clinical factors.
ABSTRACT
Intro: The ongoing pandemic caused by the SARS-CoV-2 virus has brought many new insights into medicine. During the first months of the pandemic, when there were no comprehensive guidelines for precise antimicrobial therapy, empirical overuse of broad-spectrum antibiotics was observed. Which resulted in the development of clostidium infection in certain cases. In our report, we address 83 cases of clostridial colitis in post-covid patients from 3/2020 to 3/2021 and their specific therapy. Method(s): Retrospective analysis of risk factors for clostridial infection and therapy of clostridial colitis. Finding(s): In the period 3/2020-3/2021, 9617 patients were diagnosed with SARS-CoV-2 virus infection in our hospital, of which 1247 were hospitalized. In 83 cases, clostridial colitis occurred during or after the covid infection had resolved. Mortality in this group was 17%, which corresponds to 14 patients. Previous empirical administered antiobiotics in COVID-19 infection contributed to the development of clostridial colitis in case of 22 patients (27%) by clarithromycin, in 14 pacients (17%) by penicillins and by 3rd generation cephalosporins in 9 patients (11%). The average duration of therapy with broad-spectrum antibiotics was 15.63 days (+-8.99). Other risk factors we observed are: PPI use (25%), active malignant disease (10%), previous glucocorticoid therapy (22%). Vancomycin was used in clostridial infection therapy in 47% (39), metronidazole in 31% (25) and fidaxonicin in 7% (6). In the group, we observed recurrence of clostridium difficile infection in 14% of patients and FMT was performed in 6 patients. Conclusion(s): This study shows a higher percentage of clostridial infection in cases of long-term therapy with broad-spectrum antibiotics. It also points to the effect of specific antimicrobial therapy for infection caused by the bacterium Clostridium difficile and the possibility of using fecal bacteriotherapy.Copyright © 2023
ABSTRACT
Antibiotics play an essential role in antimicrobial therapy. Among all the medications in children, the most commonly prescribed therapy is antibiotics and is currently the indispensable means to cure transmissible diseases. Several categories of antibiotics have been introduced into clinical practice to treat microbial infections. Reducing the unnecessary use of antibiotics is a global need and priority. This article aims to provide better knowledge and understanding of the impact of the early use of antibiotics. This article highlights the proper use of antibiotics in chil-dren, detailing how early and inappropriate use of antibiotics affect the gut microbiome during normal body development and consequently affect the metabolism due to diabetes mellitus, obe-sity, and recurrence of infections, such as UTI. Several new antibiotics in their development stage, newly marketed antibiotics, and some recalled and withdrawn from the market are also briefly discussed in this article. This study will help future researchers in exploring the latest information about antibiotics used in paediatrics.Copyright © 2023 Bentham Science Publishers.
ABSTRACT
Background: Bipolar electrocautery tonsillectomy has been the preferred technique for many otolaryngologists, yet coblation tonsillectomy is gaining popularity in the current practice. This study aims at comparing both techniques in terms of pain, bleeding, and healing. Result(s): A total of 120 patients were randomly divided into two equal groups. Overall mean pain score associated with coblation tonsillectomy was statistically less than that caused by bipolar electrocautery throughout the follow-up period (p < 0.001). The difference in pain duration was statistically longer for the bipolar group. The incidence of postoperative hemorrhage-both reactionary and secondary-was statistically higher in the bipolar group. Coblation tonsillectomy showed statistically shorter duration of healing (p < 0.001). Conclusion(s): Coblation tonsillectomy is associated with less pain severity and shorter pain duration, fewer bleeding incidents, and more prompt healing.Copyright © 2022, The Author(s).
ABSTRACT
COVID-19 disease is caused by the new coronavirus SARS-CoV-2. The disease first appeared in China in 2019 and quickly spread throughout the world. It primarily affects the respiratory tract, manifested by fever, cough and the devel-opment of dyspnoea, but the symptoms and complications can affect any organ system. Neurological symptoms include headaches, muscle and joint pain, taste and smell disorders. Complications include inflammatory diseases of the central nervous system, ataxia, peripheral nerve and muscle diseases, worsening of extra-pyramidal diseases, and neuropsychiatric disorders. This paper presents a case report of a 62-year-old man with cere bellar syndrome, ataxia, intentional tremor and hypermetria when dealing with COVID-19 disease.Copyright © 2021 Neuroendocrinology Letters.
ABSTRACT
Background: Currently, the present world is facing a new deadly challenge from a pandemic disease called COVID-19, which is caused by a coronavirus named SARS-CoV-2. To date, no drug or vaccine can treat COVID-19 completely, but some drugs have been used primarily, and they are in different stages of clinical trials. This review article discussed and compared those drugs which are running ahead in COVID-19 treatments. Method(s): We have explored PUBMED, SCOPUS, WEB OF SCIENCE, as well as press releases of WHO, NIH and FDA for articles related to COVID-19 and reviewed them. Result(s): Drugs like favipiravir, remdesivir, lopinavir/ritonavir, hydroxychloroquine, azithromycin, ivermectin, corticosteroids and interferons have been found effective to some extent, and partially approved by FDA and WHO to treat COVID-19 at different levels. However, some of these drugs have been disapproved later, although clinical trials are going on. In parallel, plasma therapy has been found fruitful to some extent too, and a number of vaccine trials are going on. Conclusion(s): This review article discussed the epidemiologic and mechanistic characteristics of SARS-CoV-2, and how drugs could act on this virus with the comparative discussion on progress and drawbacks of major drugs used till date, which might be beneficial for choosing therapies against COVID-19 in different countries.Copyright © 2022 Bentham Science Publishers.
ABSTRACT
Antibiotic resistance among Helicobacter pylori strains is the major cause of eradication failure. Resistance prevalence is dynamic and can greatly vary among countries over the years. We revealed H. pylori resistance trends for five antibiotics in 14 countries through articles predominantly published in 2018-2022, since the latest data can best show the most recent trends in resistance evolution. Amoxicillin resistance generally exhibited no evolution, yet it increased in Bulgaria, Iran, China, and Vietnam. Metronidazole resistance exhibited different trends, including an increase, a decrease and no evolution in six, three, and five studies, respectively. Clarithromycin resistance increased in Australia, Belgium, Bulgaria, Italy, Iran, and Taiwan, but remained stable in France, Spain, Russia, China, Chile, and Colombia. Tetracycline resistance was low and stable except in Iran. Levofloxacin resistance increased in four European and six other countries/regions, without significant increases in France, Spain, and Chile. In Chile, triple resistance also increased. In countries such as France and Spain, resistance to most antibiotics was stabilized, while in Bulgaria, Belgium, Iran and Taiwan, resistance to three or more agents was reported. Use of non-recommended regimens, national antibiotic consumption, patient's compliance, host factors, strain virulence, migrations, and azithromycin overuse during the COVID-19 pandemic can influence resistance evolution. New drugs, eradication regimens and diagnostic methods, such as next-generation sequencing can improve H. pylori infection control.
ABSTRACT
Aim: To determine the changes in the diagnoses of patients admitted to pediatric emergency department due to infection and the change in the tendency towards prescribing antibiotics during the COVID-19 pandemic.Methods: Age, gender and the diagnoses of and the antibiotics prescribed for patients under the age of 18 who admitted to the pediatric emergency department on two separate days before and during the pandemic period were compared retrospectively.Results: It was found that the admissions to the pediatric emergency department decreased by 83% during the pandemic period compared to the pre-pandemic period. Upper respiratory tract infection (URTI) was diagnosed in 61.6% of the patients during the pre-pandemic period compared to 32.6% of the patients during the pandemic periods, indicating a statistically significant difference between the groups (p<0.001). The percentage of patients diagnosed with paranasal infection in the pandemic period was also significantly lower than in the pre-pandemic period. On the other hand, the percentages of patients diagnosed with urinary infection and diagnoses other than infection in the pandemic period were significantly higher than in the pre-pandemic period. Additionally, the percentage of patients who were prescribed amoxicillin-clavulanic acid (CAM) was significantly higher, whereas the percentage of patients who were prescribed Clarithromycin was significantly lower in the pandemic period than in the pre-pandemic period. Furthermore, it was determined that Oseltamivir was not prescribed during the pandemic period.Conclusions: Quarantines imposed due to the COVID-19 pandemic and the use of masks have reduced the incidence of upper and lower respiratory tract infections. In parallel, it was determined that the percentage of patients presented to the pediatric emergency department with the diagnosis of non-infectious diagnoses has increased. This result has been attributed to the use of masks and the attention paid to the hygiene, which caused a decrease in the incidence of infectious diseases, influenza in particular.
ABSTRACT
Introduction: Severe COVID-19 viral pneumonitis, requiring invasive mechanical ventilation, has a mortality rate approaching 45%.1 The RECOVERY trial demonstrated that Dexamethasone protocol (6 mg a day for up to 10 days, commenced early) decreased 28 days' mortality for this cohort from 41.4% to 29.3% (OR 0.64;95% CI 0.51-0.81).2 More generally, a study confirmed corticosteroids' beneficial effect in COVID-19 patients which was more prominent in females, younger patients (<65) and with higher C-reactive protein (CRP) levels (in excess of 150 mg/ L). Importantly, it did not increase incidence of bacteremia or fungemia.3 In another study, responders to corticosteroids (more than 50% of CRP levels reduction in 72 hours) had reduced risk of death ( 25.2% vs. 47.8% in nonresponders;OR 0.37, P<0.001).4 In our district general hospital, the Dexamethasone protocol was introduced and used consistently at the beginning of COVID-19 second wave. Therefore, an impact of this intervention could be detected by comparing the outcomes between SaRS-CoV-2' patients admitted during Wave-1 versus Wave-2. Concomitant antibiotics (Co-amoxiclav and Clarithromycin) were introduced at the same time, but this practice varied. Objectives: To detect impact of Dexamethasone protocol on COVID-19 invasively ventilated ICU patients' outcomes by using retrospective analysis. Methods: The information on ICU mortality, peak CRP levels (irrespectively of peak-time, but most manifested within 10 days from admission) and incidence of positive blood cultures (if resulted from both sampling tubes) was collected from trust databases after the last patient's ICU discharge. Wave-1 was defined as SARS-CoV-2 PCR confirmed patients admitted to the hospital from 1/3/2020 until 31/5/ 2020. Wave-2 period was from 1/10/2020 until 28/2/2021. Mann Whitney U test was used for CRP numbers. Results: Number of ICU patients requiring mechanical ventilation: 34 (W-1) versus 39 (W-2). There was no statistical difference in age and gender. ICU mortality was: 41% (W-1) versus 44% (W-2). Incidence of bacteremia was: 24% (W-1) versus 46% (W-2). The bulk of the difference was due to coagulase negative coccal flora and Staphylococcus epidermidis;increase from 1 to 11 cases. Medians (quartiles 1 -3) of peak CRP levels were: 336 (264 -415) (W-1) versus 264 (172 -379) (W-2), P-0.042. The difference was even more pronounced when looking at peak CRPs of W-2 survivors: median 234 (150 -270). It was statistically significant for this group in comparisons between W-2 non-survivors and W-1 survivors, P -0.021 and 0.017 correspondingly. Conclusion: Our data (bearing in mind loss of some due to inter-hospital transfers and overall limited numbers) did not demonstrate any significant difference in ICU mortality of mechanically ventilated patients which could be attributed to the protocol. Statistically significant differences in average peak CRP levels between the COVID-19 waves (especially for Wave-2 ICU survivors) may be explained by the Dexamethasone protocol impact. This agrees with previous data.4 There was a significant increase in incidence of positive blood cultures due to bacterial flora usually considered contaminants.
ABSTRACT
Background: The COVID-19 pandemic has generated uncertainties and concerns along with expectations and hopes that may be of relevance to patients with rheumatic diseases. Objectives: The aim of this study is to assess changes in the fears and hopes of patients with rheumatic diseases throughout the two phases of REUMAVID. Methods: REUMAVID is an international cross-sectional study collecting data through an online survey in seven European countries led by the Health & Territory Research group of the University of Seville, together with a multidisciplinary team including patient representatives, rheumatologists, and health researchers. Data were collected in two phases: Phase 1 (P1) between April-July 2020 and Phase 2 (P2) between February-April 2021. Demographics, health behaviours, employment status, access to healthcare services, disease characteristics, WHO-5 Well-Being Index and Hospital Anxiety and Depression Scale (HADS). Participants rated a series of fears (infection, medication consequences, lack of medication, impact on healthcare, lost job, civil disorder) on a scale from zero ('no concern at all') to five ('extremely concerned') and hopes (treatment/vaccine availability, going outside, travel, economic situation, treatment continuation, health status) on a scale from zero ('no hopeful at all') to five ('extremely hopeful'). Descriptive analysis and Mann-Whitney test were used to explore fears and hopes in both phases of REUMAVID. Results: A total of 3,802 participants were recruited across both phases in REU-MAVID with comparable demographic characteristics: mean age 52.6 (P1) vs. 55.0 years (P2), 80.2% female (P1) vs. 83.7% (P2), 69.6% married (P1) vs. 68.3% (P2), and 48.6% university educated (P1) vs. 47.8% (P2). Most prevalent RMD was axial spondyloarthritis in P1 (37.2%), and rheumatoid arthritis in P2 (53.1%). In P1 and P2 the major concern was the impact on healthcare in the future (3.1 and 3.2 out of 5, p=0.051). Compared to P1, patients in P2 had less fears about RMD medications not reaching the country (2.4 vs. 1.9, p<0.001), civil disorders (2.0 vs. 1.8, p=0.001), or losing their jobs (1.4 vs. 1.5, p=0.003). Comparing hopes with P1, patients in P2 had greater hopes about availability of treatments or vaccines suitable for COVID-19 (3.2 vs. 3.9, p<0.001), to be able to go out as before the pandemic (3.1 vs. 3.5, p<0.001), to be able to travel as before the pandemic (2.8 vs. 3.3, p<0.001), maintain and even improve the current economic situation after the pandemic (2.6 vs. 3.0, p<0.001), and to be able to continue their treatment as usual (3.8 vs. 3.8, p=0.049;Table 1) Conclusion: During the frst phase of REUMAVID at the beginning of the pandemic, patients with RMDs were more fearful and less hopeful compared to the second phase. These fears were notable in terms of lack of medication for their RMD, while during the second phase, patients were hopeful of a treatment or vaccine against COVID-19, and of being able to go out and travel as before.
ABSTRACT
This study was conducted in the College of Medicine, Wasit University Cooperation with the Al Zahraa Teaching Hospital, Al Kut Hospital laboratory in Wasit, Al-Karama hospital and private clinics of internal from the period of November 2020 to April 2021. It has been carried out on 150 samples of nasal and throat swabs from post COVID-19 patients who suffered from nasal and throat infection from both sex (male &female). The infections were in age group between (4-88) years. The results of throat swabs showed that 84(56%) were infected with bacteria and 66(44%) non-infected and the results of nasal swabs showed that 67(44.66%) were infected with bacteria and 83(55.33%) non-infected. The results of culture appeared that from 150 throat swab sample found that 66(44%) samples were no growth and 84(56%) were infected with bacteria. The results were Pseudomonas aeruginosa 12/150(8%), E. coli 9/150(6%), Enterobacter spp. 2/150(1.33), Pseudomonas spp. 2/ 150(1.33%), Klebsiella spp. 2/150(1.33%), Staphylococcus spp. 4/150(2.66%), Staphylococcus aureus 4/150(2.66%), Streptococcus viridans 43/150(28.66%) and mix of Staphylococcus spp. and Streptococcus viridans 6/150(4%). Out of 150 nasal swab sample found that 83/150(55.33%) sample were no growth and 67/150(44.67%) were infected with bacteria. The result were Pseudomonas aeruginosa 7/150(4.66%), E.coli 3/150(2%), Enterobacter spp. 2/150(1.33), Pseudomonas spp. 5/ 150(3.33%), Klebsiella spp. 6/150(4%), Staphylococcus spp. 12/150(8%), Staphylococcus aureus 3/150(2%), Streptococcus viridans 24/150(16%) and mix of Staphylococcus spp. and Streptococcus viridans 3/150(5.33%) and mix of E. coli and Pseudomonas spp. 2/150(1.33%). Antimicrobial sensitivity for Pseudomonas aeruginosa showed sensitivity to Amikacin (100%), levofloxacin (90%), Meropenem (90%), Cefipime (70%), Imipenem (60%), Aztreonam (30%), Chloramphenicol (5%), and don’t show sensitive to Tetracycline, Pipracillin, Ampicillin, Trimethoprim-Sulphamethoxazole and Clarithromycin. To facilitate species identification, used molecular methods (PCR analysis) by 16s rRNA primers gene for more predominant bacteria isolates (Pseudomonas aeruginosa) isolates studied were detected by 16S rRNA gene and there virulence factors based on multiplex polymerase chain reaction technique amplifying five virulence factors primer for Pseudomonas aeruginosa (aprA, filC, toxA, pilA, pslA). In this study, we concluded that the production of virulence factors genes in Pseudomonas aeruginosa is important to human infection especially (ToxA) gene and the PCR technique was very specific and fast method in detection virulence factor genes in Pseudomonas aeruginosa.
ABSTRACT
Azithromycin (AM) detection has become of great interest as being one of the prescribed medicines in the medication protocol in Egypt for the recent coronavirus disease 2019 pandemic. Herein, a carbon paste electrode was simply amended with fumed silica for determining AM. The characterization of the new material was done by different techniques, including scanning electron microscopy, transmission electron microscopy, and electrochemical impedance spectroscopy. The newly modified fumed silica carbon paste electrode exhibited a highly sensitive response toward the oxidation of 1.0 mmol/L AM in phosphate buffer solution (PBS) for a pH range of 5.0-10.0. The effect of varying AM concentrations was studied in PBS, pH 7.4, with a detection limit of 11 mu mol/L and a quantification limit of 37 mu mol/L. Eventually, the recently amended electrode attained reasonable sensitivity and constancy for AM detection in actual trials, such as blood plasma and pharmaceutical drugs.
ABSTRACT
This article is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Review previously published in the Cochrane Database of Systematic Reviews. Original publication: Popp M, Stegemann M, Riemer M, Metzendorf MI, Romero CS, Mikolajewska A, et al. Antibiotics for the treatment of COVID-19. Cochrane Database of Systematic Reviews.
ABSTRACT
Introduction: Gastrointestinal symptomatology in SARS-CoV-2 infection is a common clinical presentation, reported in up to 61% in those affected, being the presence of acute diarrhea one of the most common symptoms, reported in up to 33.7%. There are multiple theories about physiopathological mechanisms of diarrhea associated with SARS-CoV2 infection, but there is not enough evidence to attribute this symptom only to the infection without the influence of host and environment factors. Objective: Determine the associated factors with acute diarrhea in Mexican population with SARS-CoV-2 infection. Methods: A case-control cross-sectional study was performed to analyze the factors associated with acute diarrhea in patients with SARS-CoV-2. This research was carried out during the 2020-2021 in five states of Mexico. An online survey was applied to 784 patients, selected by randomized sampling of whom sociodemographic data, medical history, and symptoms related to SARSCoV- 2 infection were collected. A univariate and multivariate logistic regression analysis was performed applying a χ2 test with 95% confidence intervals to determinate the association of acute diarrhea in SARS-CoV-2 infection with other symptomatology and possible nonhost contributing factors for its presentation. Results: A total of 784 patients were analyzed with a mean age of 29 ± 8 years, predominantly female with 75.4% (591). The most frequently described symptom was fatigue in 75% (588) followed by anosmia and myalgias with 67% (525) and 65.5% (514) respectively. Acute diarrhea was present in 28.6% (321) of our population during the acute phase of SARS-CoV-2 infection. The most used drugs were acetaminophen (79.2%) and azithromycin (29.7%). The multivariate logistic regression analysis showed a statistically significant association between acute diarrhea and the use of macrolides, mainly with clarithromycin with an OR of 2.96 (95% CI of 1.26-6.95, p = 0.001) followed by azithromycin with an OR of 1.47 (95% CI 1.035-2.091, p = 0.031). In this same analysis, there was no significant association of acute diarrhea with the rest of SARS-CoV-2 infection symptoms. Discussion: This study demonstrates the association of acute diarrhea in SARS-CoV-2 infection with the concomitant use of macrolides, without finding any association with described SARS-CoV-2 viral symptoms. According to the previously mentioned, we propose that a proportion of acute diarrhea associated with SARSCoV- 2 infection may be secondary to inappropriate macrolide prescription and not due to the viral disease itself.
ABSTRACT
BACKGROUND: Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple organ dysfunction syndrome. METHODS: We conducted a multicenter, randomized, clinical trial in patients with sepsis. Participants with ratio of partial oxygen pressure to fraction of inspired oxygen less than 200 and more than 3 SOFA points from systems other than the respiratory function were enrolled between December 2017 and September 2019. Patients were randomized to receive 1 gr of clarithromycin or placebo intravenously once daily for 4 consecutive days. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 90-day mortality; sepsis response (defined as at least 25% decrease in SOFA score by day 7); sepsis recurrence; and differences in peripheral blood cell populations and leukocyte transcriptomics. RESULTS: Fifty-five patients were allocated to each arm. By day 28, 27 (49.1%) patients in the clarithromycin and 25 (45.5%) in the placebo group died (risk difference 3.6% [95% confidence interval (CI) - 15.7 to 22.7]; P = 0.703, adjusted OR 1.03 [95%CI 0.35-3.06]; P = 0.959). There were no statistical differences in 90-day mortality and sepsis response. Clarithromycin was associated with lower incidence of sepsis recurrence (OR 0.21 [95%CI 0.06-0.68]; P = 0.012); significant increase in monocyte HLA-DR expression; expansion of non-classical monocytes; and upregulation of genes involved in cholesterol homeostasis. Serious and non-serious adverse events were equally distributed. CONCLUSIONS: Clarithromycin did not reduce mortality among patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration. Clinical trial registration clinicaltrials.gov identifier NCT03345992 registered 17 November 2017; EudraCT 2017-001056-55.
Subject(s)
Clarithromycin , Sepsis , Administration, Intravenous , Clarithromycin/pharmacology , Clarithromycin/therapeutic use , Humans , Multiple Organ Failure/complications , Multiple Organ Failure/drug therapy , Oxygen/therapeutic use , Sepsis/complicationsABSTRACT
Background: Secondary antibody deficiency (SAD) is typical of hematological malignancies, such as chronic lymphocytic leukemia (CLL), multiple myeloma, and lymphoma or as a side effect of their treatment. Immunological defects are observed in 25-85% of CLL patients (pts), both naïve and previously treated, depending on duration, stage of disease, treatment, patient's age, and comorbidities. (Na et al., 2019;Patel et al., 2019;Zinzani et al., 2019;Reiser et al., 2017). In CLL pts, SAD increases the risk of infections, with overall higher morbidity and mortality Antibiotics administration and vaccinations are recommended as risk-reduction strategies. No real guidelines are available, but many indications warrant immunoglobulins replacement therapy (IgRT) in selected pts with low IgG (<5 g/l) or with more than three infective episodes per year despite antibiotic treatment and timely vaccination (Na et al., 2019;Reiser et al., 2017). No clear indications are available regarding the delivery method (intravenous or subcutaneous), dosage, frequency of administration, and duration of IgRT. Aims: The aim of this study is to assess the efficacy and the safety of SCIg on CLL patients in terms of infectious events, immune recovery and lymphocytes subset, impact on quality of life (QoL) on CLL pts in the Covid-19 era. Methods: Ten CLL pts with SAD have been treated with subcutaneous IgRT (SCIg) from October 2019 to December 2020. The median age and body weight of the pts were 66 years (56-88) and 68 kg (52-86) respectively. Five patients had comorbidities (hypertension, diabetes mellitus, and lung diseases) and 90% of them had an Eastern Cooperative Oncology Group (ECOG) performance 0-1. Five pts presented with unmutated IgVH and one of them also had 17p deletion. The median number of prior therapies was 2 (IBR, BR, Chl-antiCD20, FCR, in 5, 4, 4, 3 pts, respectively). At that time, 7 pts were on therapy (IBR, Ven, Alkylating Agent in 4, 1, 2 pts, respectively). None presented neutropenia. All pts underwent antibiotic prophylaxis with trimetroprin-cotimoxazole, sometimes associated with clarithromycin, and influenza vaccinations. The median baseline IgG level was 485mg/dl (118-817), with a median of 3 infection/year (1-5;pneumonia, UTI). Patients' characteristics are reported in Table 1. All pts received 10 g total dose hyaluronidase-free SCIg over a 1 h in double-needle subcutaneous infusion every 15 days for one year, independently from body weight. After the first dose, administered in a hospital setting to make the patient comfortable with their personal pump, the next doses were self-administered at home. The IgG level and CD4/CD8, CD19, and CD16/56 (natural killer, NK) lymphocytes subset were recorded at baseline and every three months during the observation period to monitor the immunological reconstitution as the therapy went on. Results: In our monocentric experience from October 2019 to December 2020 no patient experienced infectious events nor Covid-19 mediated interstitial pneumonia while on SCIg therapy. All patients tolerated well the therapy: nobody interrupted the treatment and only one patient presented a skin rash (grade 2). Both dosage and administration schedule have been stable over time. Dealing with humoral immunity, IgG levels arose from a median of 485 (118-817) mg/dl to a stable median value >600 mg/dl from 6 months onward. As expected, IgA and IgM values remained below normal levels. Dealing with cellular immunity, T-cells including CD4, CD8, and natural killer (NK, CD16/56) cells displayed a stable fashion until 6 months. On the other hand, the CD19 B cells values reflect both the disease status and the ongoing treatment effects. Results are reported in Table 1. Finally, we observed advantages on adherence to treatment, QoL, and costs, since pts did not need to go to the hospital with the help of a care-giver, rather they could comfortably get their SCIg at home without any assistance. Conclusion: SCIg administration in CLL pts with SAD is efficacious and safe as infectious prophylaxis, with hig er median IgG levels, thanks to both pharmacokinetic advantages and improved adherence to treatment. Especially in the Covid-19 era, the subcutaneous route is preferred to the intravenous one, because of the self-administration at home and the granted availability to the drug itself. Finally, subcutaneous administration gives advantages to the QoL and hospital expenditure.
ABSTRACT
Introduction: Increase in cases with chilblain-like acral lesions has been observed during the pandemic period. Epidemiological data suggest that children have different immunological responses to SARS-CoV-2 virus, which can cause mild respiratory illness but more frequently involve other organ systems. Co-infection of SARS-CoV-2 with Chlamydia or Mycoplasma pneumoniae has been described both in adults and pediatrics (1). Objectives: To analyze clinical features, laboratory and instrumental findings of a group of patients with chilblain-like lesions during SARS-CoV-2 pandemic period. Methods: Retrospective analysis of 4 patients with chilblain-like lesions. Results: We present 4 patients with chilblain-like acral lesions (2 female and 2 male). The median age was 15.5 years (13 to 16 years old). Two patients had lesions only in toes whilst others had both hand and feet perniosis. All patients had no laboratorical signs of inflammation (CRP, ESR, WBC, neutrophil, and lymphocyte count were in normal range) and markers for rheumatic and connective tissue diseases (cryoglobulins, antinuclear antibodies, anti-double-stranded DNA antibodies, antineutrophil cytoplasmic antibodies, rheumatoid factor) were negative. Levels of serum complement C3 (mean value 0.775 g/l) and complement C4 (mean value 0.1425 g/l) was reduced in all cases. Two patients had positive Chlamydia pneumonia antibodies (IgM titers of >12 were defined as positive), others were not tested. The first patient had lesions in toes and for the second patient, both hands and feet were damaged. All patients underwent ultrasound of affected sites. One of 4 patients was diagnosed with reactive arthritis in metatarsophalangeal joints in ultrasound and MRI. There was no epidemiological anamnesis or clinical manifestation or any evidence of SARS-CoV-2 infection (SARS-CoV-2 antibodies were negative) for all patients. Also, there was no anamnesis of any respiratory tract symptoms or diagnosed infection in the last 4 months in all patients. Patients with C. pneumoniae IgM antibodies positive were given a course of clarithromycin. Despite the prescribed course of antibiotics, the skin lesions remained. One patient with arthritis was treated with NSAIDs. Others resolved by themselves without requiring any treatment. Conclusion: Chilblain-like lesions in the skin can be one of the signs of previous SARS-CoV-2 infection despite negative virus antibodies (2). Possible hypothesis is a high production of type I interferon (IFN) associates with early viral control and suppression of antibody production. A strong IFN response can cause skin manifestations (3). Coinfection with other atypical bacteria can intensify immune complexes formation and skin injury (4). This phenomenon can be observed with low levels of C3 and C4 in blood samples.
ABSTRACT
INTRODUCTION: The anti-inflammatory effect of macrolides prompted the study of oral clarithromycin in moderate COVID-19. METHODS: An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the end of treatment (EOT) as no need for hospital re-admission and no progression into lower respiratory tract infection (LRTI) for patients with upper respiratory tract infection and as at least 50% decrease of the respiratory symptoms score without progression into severe respiratory failure (SRF) for patients with LRTI. Viral load, biomarkers, the function of mononuclear cells and safety were assessed. RESULTS: The primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1-92.2%); this was 91.7% and 81.4% among patients starting clarithromycin the first 5 days from symptoms onset or later (odds ratio after multivariate analysis 6.62; p 0.030). The responses were better for patients infected by non-B1.1 variants. Clarithromycin use was associated with decreases in circulating C-reactive protein, tumour necrosis factor-alpha and interleukin (IL)-6; by increase of production of interferon-gamma and decrease of production of interleukin-6 by mononuclear cells; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported. CONCLUSIONS: Early clarithromycin treatment provides most of the clinical improvement in moderate COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04398004.
ABSTRACT
In light of the accumulating evidence for survival benefit coming from the use of macrolides for community-acquired pneumonia (CAP), a group of experts from the field of internal medicine and infectious diseases frame a position statement on the use of macrolides for the management of bacterial CAP and for infection by the novel coronavirus (COVID-19). The statement is framed taking into consideration existing publications and own research experience. The main content of this statement is that the combination of one ß-lactam and a macrolide should be the first treatment of choice for patients with severe bacterial CAP. Severity is assessed as scoring 2 or more points on the CURB65 scoring system of severity or as pneumonia severity index III to V or C-reactive protein more than 150 mg/l; the suggested macrolide is either azithromycin or clarithromycin. The experts also suggest that in COVID-19 pneumonia, the combination of one ß-lactam and a macrolide should be reserved only when there is strong suspicion of bacterial co-infection.