Infections caused by Haemophilus ducreyi: one organism, two stories.

SUMMARYChancroid, a sexually transmitted infection caused by Haemophilus ducreyi, is characterized by painful genital ulcers (GU) and inguinal lymphadenitis. H. ducreyi was recently described as a major cause of non-sexually transmitted cutaneous ulcers (CU) on the lower legs in children in yaws-endemic regions. This review explores the relationship between CU and GU strains of H. ducreyi; their clinical presentation, diagnosis, epidemiology, and treatment; and how findings from a human challenge model relate to GU and CU. We contrast the decline of GU with the persistence of CU caused by H. ducreyi. Factors such as transmission dynamics, control, and elimination efforts are discussed. Syndromic management and targeted treatment of sex workers can eradicate chancroid, while skin colonization by CU strains and environmental factors may necessitate topical treatments or vaccination for CU eradication. Efforts should focus on identifying additional reservoirs of CU strains, improving hygiene, and eliminating asymptomatic colonization to eradicate this painful infection in children.

Perspective on the challenges of COVID-19 facing healthcare workers.

The emergence of COVID-19 has caused a significant impact on healthcare workers (HCWs) across the globe. A few of these challenges include high workload, lack of coordination and direction, changing information, shortage of personal protective equipment (PPE), managing isolation, fear, and increased anxiety, adapting to changes in healthcare practice and policy, coping strategies, and emotional and physical needs. Here, we shed light on some aspects of these challenges among healthcare workers.

Carbapenem use correlates with percentage of patients with COVID-19 in intensive care units.

BACKGROUND: The first wave of COVID-19 pandemic may have significantly impacted antimicrobial consumption in hospitals. The objective of this study was to assess the evolution of carbapenem consumption and describe the implemented measures during the first year of the COVID-19 pandemic. METHODS: We calculated carbapenem consumption for all the hospital and for intensive care units (ICU) for three periods: baseline (before COVID-19 cases, January 2019-February 2020), and the period of COVID-19 cases as a pre-intervention (March-August 2020) and a post-intervention phase (September 2020-December 2021). RESULTS: During the study period, the percentage of admitted COVID-19 patients increased in the months of April-August of 2020 (pre-intervention period) from 5 to 26% of total admitted patients. The consumption of carbapenems (DDD/1000 patient days) increased from a mean of 67.1 at baseline to 142.9 pre-intervention. In ICUS, there was an increase in the mean from 125.7 to 240.8 DDD/1000 patient days. After interventions, the DDD/1000 patient days decreased by 49.5% overall the hospital and by 36% in ICUs. For the post-intervention period, there was a correlation between COVID-19 cases and carbapenem usage in the ICU but not the overall hospital. CONCLUSION: An increase in the antimicrobial consumption during the first wave of COVID-19 pandemic was noticed, especially in the ICU. Antimicrobial stewardship programs are essential to reduce consumption rate.

COVID-19 and other respiratory tract infections at mass gathering religious and sporting events.

PURPOSE OF REVIEW: Mass gathering (MG) religious events provide ideal conditions for transmission and globalization of respiratory tract infections (RTIs). We review recent literature on COVID-19 and other RTIs at recurring international annual MG religious and sporting events. RECENT FINDINGS: Due to the COVID-19 pandemic organizers of MG religious and sporting events introduced risk-based infection control measures that limited transmission of RTIs. The 2020 and 2021 Hajj were conducted with limited numbers of pilgrims compared to the annual millions of pilgrims. The Tokyo 2020 Olympic and Paralympic Games were cancelled and held in 2021. The success of the COVID-19 countermeasures at the 2021 Hajj and 2021 Tokyo Olympics was based on implementing good public health and social measures alongside a comprehensive testing strategy. SUMMARY: MG events are associated with transmission of a range of bacterial and viral RTIs. Introducing risk based a multitude of public health interventions can reduce transmission of SARS-CoV-2 and other RTIs.

Antibiotics in the pipeline: a literature review (2017-2020).

INTRODUCTION: Antimicrobial resistance (AMR) is an emerging global threat. It increases mortality and morbidity and strains healthcare systems. Health care professionals can counter the rising AMR by promoting antibiotic stewardship and facilitating new drug development. Even with the economic and scientific challenges, it is reassuring that new agents continue to be developed. METHODS: This review addresses new antibiotics in the pipeline. We conducted a review of the literature including Medline, Clinicaltrials.org, and relevant pharmaceutical companies for approved and in pipeline antibiotics in phase 3 or new drug application (NDA). RESULTS: We found a number of new antibiotics and reviewed their current development status, mode of action, spectra of activity, and indications for which they have been approved. The included studies from phase 3 clinical trials were mainly utilized for the treatment of acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, and pneumonia acquired in the healthcare settings. The number of these agents is limited against high priority organisms. The identified antibiotics were based mainly on previously known molecules or pre-existing antimicrobial agents. CONCLUSION: There are a limited number of antibiotics against high priority organisms such as multi-drug-resistant Pseudomonas aeruginosa, and carbapenem-resistant Enterobacteriaceae. New antimicrobial agents directed against the top priority organisms as classified by the World Health Organization are urgently needed.

Post-COVID-19 syndrome: assessment of short- and long-term post-recovery symptoms in recovered cases in Saudi Arabia.

INTRODUCTION: Recent studies investigated the endurance of symptoms and occurrence of complications three months after SARS-CoV-2 infection. This study aims to examine the prevalence, variation, and severity of continual symptoms in the post-COVID-19 using a single-center questionnaire. METHODS: The questionnaire was distributed among population in Saudi Arabia who recovered from COVID-19 between April 1, 2020 and December 31, 2021. RESULTS: A total of 744 participants completed the questionnaire, 318 (42.8%) recovered less than 3 months, 75 (10.1%) recovered 3-6 months, while 351 (47.2%) recovered more than 6 months. About half of the participants 353 (47.5%) had incessant symptoms and of those patients, more than half had two or more symptoms. Common symptoms included fatigue 189 (25.4%), headache 118 (15.9%), and myalgia 63 (8.5%). Of the participants, 189 (21.4%) experienced continual symptoms including anxiety in 98 (13.2%) and depression in 70 (9.5%). CONCLUSION: The current study showed a high proportion of individuals with long-COVID-19 symptoms. Thus, proper assessment of the individuals in the post-recovery period can guide the patients to the relevant clinics for rehabilitation. Moreover, there is a great importance to decrease COVID-19 infection, populations should be targeted to boost vaccine efficiency.

Implication of the emergence of the delta (B.1.617.2) variants on vaccine effectiveness.

INTRODUCTION: COVID-19 vaccines have been developed to compact the current SARS-CoV-2 pandemic and have been administered to people all over the world. These vaccines have been quite effective in reducing the possibility of severe illness, hospitalization and death. However, the recent emergence of Variants of Concern specifically the delta variant, B.1.617.2, had resulted in additional waves of the pandemic. METHODS: We aim to review the literature to understand the transmission and disease severity, and determine the efficacy of the current COVID-19 vaccines. We searched Pubmed, Scopus, and Embase till August 4th 2021, and used the search terms "delta variant", "vaccinations"," breakthrough infections", and "neutralizing antibody". For the meta-analysis, 21 studies were screened in particular and five articles (148,071 cases) were included in the study, and only four were analyzed in the meta-analysis. RESULTS: In this review, both in vitro and in vivo studies showed significant reductions in neutralization rates against delta variants for vaccinated individuals and convalescent patients with prior history of COVID-19. However, There was a lower incidence of infection with SARS-CoV-2 due to Delta variant was found after the second dose of Pfizer-BioNTech, Oxford-AstraZeneca and Moderna vaccines. CONCLUSION: In fully vaccinated individuals, symptomatic infection with the delta variant was significantly reduced, and therefore, vaccinations play an important role to assist the fight against delta variant.

High seroprevalence of SARS-CoV-2 among high-density communities in Saudi Arabia.

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection had been investigated utilizing serology. MATERIALS AND METHODS: This community-based sero-survey was carried out in the neighborhoods of three cities in Saudi Arabia. RESULTS: Of 5629 participants, 2766 (49.1%) were women; and 2148 (38.1%) were 18-34 years of age, and 3645 (64.7%) were from South East Asia. Positive serology was seen in 2825 (50.2% (95% CI: 48.8-51.5%) for SARS-CoV-2 anti-S1 IgG antibodies by ECLIA. Being in the age category of 18-34 years and being from Eastern Mediterranean Region (country A) were associated with higher COVID-19 seropositivity with estimated odds ratio of 1.3 [95% CI 1.1-1.8] and 2.5 [95% CI 1.1.5-4.2] respectively. Gender, social status, education, nationality, symptoms, presence of comorbidities and activity style were positively associated with increased seropositivity. Factors associated negatively with the rate of seropositivity were higher education and having outdoor activity with estimated OR of 0.92 [95% CI 0.46-0.95] and 0.59 [95% CI 0.47-0.74], respectively. CONCLUSION: The study showed high seroprevalence of SARS-CoV-2 among high density population. Health education campaigns should target middle-aged, those with low education, those living in lower standards and indoor workers.

New-onset and relapsed liver diseases following COVID-19 vaccination: a systematic review.

BACKGROUND: Liver diseases post-COVID-19 vaccination is extremely rare but can occur. A growing body of evidence has indicated that portal vein thrombosis, autoimmune hepatitis, raised liver enzymes and liver injuries, etc., may be potential consequence of COVID-19 vaccines. OBJECTIVES: To describe the results of a systematic review for new-onset and relapsed liver disease following COVID-19 vaccination. METHODS: For this systematic review, we searched Proquest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses PRISMA guideline for studies on the incidence of new onset or relapsed liver diseases post-COVID-19 vaccination, published from December 1, 2020 to July 31, 2022, with English language restriction. RESULTS: Two hundred seventy-five cases from one hundred and eighteen articles were included in the qualitative synthesis of this systematic review. Autoimmune hepatitis (138 cases) was the most frequent pathology observed post-COVID-19 vaccination, followed by portal vein thrombosis (52 cases), raised liver enzymes (26 cases) and liver injury (21 cases). Other cases include splanchnic vein thrombosis, acute cellular rejection of the liver, jaundice, hepatomegaly, acute hepatic failure and hepatic porphyria. Mortality was reported in any of the included cases for acute hepatic failure (n = 4, 50%), portal vein thrombosis (n = 25, 48.1%), splanchnic vein thrombosis (n = 6, 42.8%), jaundice (n = 1, 12.5%), raised liver enzymes (n = 2, 7.7%), and autoimmune hepatitis (n = 3, 2.2%). Most patients were easily treated without any serious complications, recovered and did not require long-term hepatic therapy. CONCLUSION: Reported evidence of liver diseases post-COIVD-19 vaccination should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively very small in relation to the hundreds of millions of vaccinations that have occurred and the protective benefits offered by COVID-19 vaccination far outweigh the risks.

Frequency of bacteremia in patients with sickle cell disease: a longitudinal study.

Bacterial infections in sickle cell disease (SCD) are associated with major risks of morbidity and mortality. Here, we describe the occurrence of bacteremia in SCD patients from 2000 to 2017. This is an observational study which included children and adults with SCD and fever and had confirmed positive blood cultures. During the study period, there were 1095 SCD patients with 17,053 blood cultures. Of all the patients, 699 (63.8%) were children and 396 (36.2%) adults with 576 (52.6%) males and 519 (47.4%) females. The mean age ± SD was 17.8 (± 14.7), and a median age (IQR) of 13.6 (6.8-23.5) years. The mean (SD) follow up was 7.4 (5.4) years and the total number of patient-years was 8069.1 years. Out of the 1095 patients, 91 (8.3%) had bacteremia with 35 (38.5%) children and 65 (61.5%) adults (p = .079). The rate of bacteremia in all patients, children, and adults were 1.5 (95% CI: 1.3-1.8), 0.6 (95% CI: 0.4-0.8), and 2.4 (95% CI: 1.8-3.1) per 100 patient-years, respectively. The risk of Gram-positive bacteremia was 0.5 (96% CI: 0.36-0.69) in all patients, 0.1 (95% CI: 0.06-0.20) in children, and 1.4 (95% CI: 1.0-2.0) in adults per 100 patient-years. The risk of Gram-negative bacteremia was 1.0 (95% CI: 0.81-1.3) in all patients, 0.6 (95% CI: 0.4-0.8) in children, and 2 (95% CI: 1.5-2.7) in adults per 100 patient-years. The risk of Gram-negative bacteremia was higher than Gram-positive bacteremia in children (p < .001) but not in adults (p = .113) and adults had higher risk in general than children. In this study of SCD cohort, 8.3% had bacteremia with predominant Gram-negative infections. Bacteremia was more frequently encountered in the adult age group. Further studies are needed to verify the findings and explore possible reasons predisposing SCD patients to bacteremia.

COVID-19 and mucormycosis superinfection: the perfect storm.

BACKGROUND: The recent emergence of the Coronavirus Disease (COVID-19) disease had been associated with reports of fungal infections such as aspergillosis and mucormycosis especially among critically ill patients treated with steroids. The recent surge in cases of COVID-19 in India during the second wave of the pandemic had been associated with increased reporting of invasive mucormycosis post COVID-19. There are multiple case reports and case series describing mucormycosis in COVID-19. PURPOSE: In this review, we included most recent reported case reports and case-series of mucormycosis among patients with COVID-19 and describe the clinical features and outcome. RESULTS: Many  of the mucormycosis reports were eported from India, especially in COVID-19 patients who were treated and recovered patients. The most commonly reported infection sites were rhino-orbital/rhino-cerebral mucormycosis. Those patients  were diabetic and had corticosteroids therapy for controlling the severity of COVID-19, leading to a higher fatality in such cases and complicating the pandemic scenario. The triad of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), corticosteroid use and uncontrolled diabetes mellitus have been evident for significant increase in the incidence of angioinvasive maxillofacial mucormycosis.  In addition, the presence of spores and other factors might play a role as well. CONCLUSION: With the ongoing COVID-19 pandemic and increasing number of critically ill patients infected with SARS-CoV-2, it is important to develop a risk-based approach for patients at risk of mucormycosis based on the epidemiological burden of mucormycosis, prevalence of diabetes mellitus, COVID-19 disease severity and use of immune modulating agents including the combined use of corticosteroids and immunosuppressive agents in patients with cancer and transplants.

Middle East Respiratory Syndrome Coronavirus.

The past two decades have witnessed the emergence of three zoonotic coronaviruses which have jumped species to cause lethal disease in humans: severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. MERS-CoV emerged in Saudi Arabia in 2012 and the origins of MERS-CoV are not fully understood. Genomic analysis indicates it originated in bats and transmitted to camels. Human-to-human transmission occurs in varying frequency, being highest in healthcare environment and to a lesser degree in the community and among family members. Several nosocomial outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by World Health Organization as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. MERS-CoV has been identified in dromedaries in several countries in the Middle East, Africa, and South Asia. MERS-CoV-2 causes a wide range of clinical presentations, although the respiratory system is predominantly affected. There are no specific antiviral treatments, although recent trials indicate that combination antivirals may be useful in severely ill patients. Diagnosing MERS-CoV early and implementation infection control measures are critical to preventing hospital-associated outbreaks. Preventing MERS relies on avoiding unpasteurized or uncooked animal products, practicing safe hygiene habits in health care settings and around dromedaries, community education and awareness training for health workers, as well as implementing effective control measures. Effective vaccines for MERS-COV are urgently needed but still under development.

Middle East Respiratory Syndrome Coronavirus and Severe Acute Respiratory Syndrome Coronavirus.

Emerging infectious diseases continue to be of a significant importance worldwide with the potential to cause major outbreaks and global pandemics. In 2002, the world had witnessed the appearance of the severe acute respiratory syndrome coronavirus in China which disappeared abruptly within 6 months. About a decade later, a new and emerging novel coronavirus named the Middle East respiratory syndrome coronavirus (MERS-CoV) was described in a patient from Saudi Arabia. These two coronaviruses shared multiple similarities in the epidemiology, clinical presentations, and posed challenges in its prevention and management. Seven years since its discovery, MERS-CoV continues to be a lethal zoonotic pathogen capable of causing severe pneumonia with high case fatality rates and the ability to cause large health care-associated outbreaks.

Successful treatment of extra-pulmonary tuberculosis presenting concomitantly with acute myeloid leukemia.

PURPOSE: There were reports of the occurrence of TB during therapy for leukemia with possible complications. In patients with acute leukemia, therapy might be delayed or complicated by the presence of tuberculosis. METHOD: We present a patient who was diagnosed with acute leukemia and concomitant tuberculosis. RESULTS: The patient's therapy of leukemia had to be delayed and he had relapse of leukemia but was subsequently treated successfully for both diseases despite a prolonged culture positivity for tuberculosis. He required a prolonged course of therapy and additional secondary anti-tuberculosis therapy. CONCLUSIONS: The possibility of tuberculosis should be considered in the differential diagnosis of patients with pneumonia, persistent fever, and those with focal signs or symptoms suggestive of tuberculosis. Despite having a sensitive organism, the infection was difficult to treat, even with the addition of two second-line drugs. The standard anti-tuberculosis therapy is usually adequate, but response may be slow, and inadequate even if the organism is sensitive requiring the addition of second-line agents.

Impact of carbapenem versus non-carbapenem treatment on the rates of superinfection: A meta-analysis of randomized controlled trials.

Imipenem and meropenem are the recommended antipseudomonal carbapenems for nosocomial pneumonia per clinical practice guidelines. However, these agents have a relatively broader spectrum of activity than other antibiotics and need to be reserved. Carbapenems might cause higher rate of superinfection. The aim of this study was to compare the rate of superinfection between patients who received imipenem or meropenem versus those who received non-carbapenem treatment. PubMed, EMBASE, Cochrane Library databases and two trial registries were searched for relevant randomized controlled trials of hospitalized adults with pneumonia through February 24, 2017 without date or language restrictions. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using random-effects models. The primary outcome was based on the intention-to-treat analysis while clinically evaluable patients were analyzed as secondary outcome. Eight RCTs were included in this meta-analysis. A statistically higher risk of superinfection with low heterogeneity (RR = 1.690, 95% CI 1.247-2.291, p = 0.001, I2 = 0%) was associated with the two carbapenems compared to non-carbapenems. However, in comparison with non-carbapenems, superinfection with imipenem was significantly higher (RR = 1.694, 95% CI 1.234-2.325, p = 0.001, I2 = 0%), while it was non-significant with meropenem (RR = 1.647, 95% CI 0.552-4.919, p = 0.371, I2 = 0%). Superinfection was statistically higher in both double-blind and open-label studies and when carbapenems were compared to other antipseudomonal beta-lactams. This meta-analysis identified significantly higher superinfection with imipenem compared to non-carbapenems. The findings confirm the theory of higher superinfections with broader spectrum agents and provide additional support for reserving carbapenems for the treatment of infections caused by multidrug-resistant organisms.

Transmission of MERS-coronavirus in household contacts.

BACKGROUND: Strategies to contain the Middle East respiratory syndrome coronavirus (MERS-CoV) depend on knowledge of the rate of human-to-human transmission, including subclinical infections. A lack of serologic tools has hindered targeted studies of transmission. METHODS: We studied 26 index patients with MERS-CoV infection and their 280 household contacts. The median time from the onset of symptoms in index patients to the latest blood sampling in contact patients was 17.5 days (range, 5 to 216; mean, 34.4). Probable cases of secondary transmission were identified on the basis of reactivity in two reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays with independent RNA extraction from throat swabs or reactivity on enzyme-linked immunosorbent assay against MERS-CoV S1 antigen, supported by reactivity on recombinant S-protein immunofluorescence and demonstration of neutralization of more than 50% of the infectious virus seed dose on plaque-reduction neutralization testing. RESULTS: Among the 280 household contacts of the 26 index patients, there were 12 probable cases of secondary transmission (4%; 95% confidence interval, 2 to 7). Of these cases, 7 were identified by means of RT-PCR, all in samples obtained within 14 days after the onset of symptoms in index patients, and 5 were identified by means of serologic analysis, all in samples obtained 13 days or more after symptom onset in index patients. Probable cases of secondary transmission occurred in 6 of 26 clusters (23%). Serologic results in contacts who were sampled 13 days or more after exposure were similar to overall study results for combined RT-PCR and serologic testing. CONCLUSIONS: The rate of secondary transmission among household contacts of patients with MERS-CoV infection has been approximately 5%. Our data provide insight into the rate of subclinical transmission of MERS-CoV in the home.

Middle East Respiratory Syndrome Coronavirus and Pulmonary Tuberculosis Coinfection: Implications for Infection Control.

Coinfection of Middle East respiratory syndrome coronavirus (MERS-CoV) with tuberculosis (TB) has not been previously reported. Here, we present 2 cases with both MERS-CoV and pulmonary TB. The first case was a 13-year-old patient who was admitted with a 2-month history of fever, weight loss, night sweats, and cough. The second patient was a 30-year-old female who had a 4-week history of cough associated with shortness of breath and weight loss of 2 kg. The 2 patients were diagnosed with pulmonary TB and had positive MERS-CoV. Both patients were discharged to complete their therapy for TB at home. It is likely that both patients had pulmonary TB initially as they had prolonged symptoms and they subsequently developed MERS-CoV infection. It is important to carefully evaluate suspected MERS-CoV patients for the presence of other infectious diseases, such as TB, especially if cohorting is done for suspected MERS-CoV to avoid nosocomial transmission.

Viral Shedding and Antibody Response in 37 Patients With Middle East Respiratory Syndrome Coronavirus Infection.

BACKGROUND: The Middle East respiratory syndrome (MERS) coronavirus causes isolated cases and outbreaks of severe respiratory disease. Essential features of the natural history of disease are poorly understood. METHODS: We studied 37 adult patients infected with MERS coronavirus for viral load in the lower and upper respiratory tracts (LRT and URT, respectively), blood, stool, and urine. Antibodies and serum neutralizing activities were determined over the course of disease. RESULTS: One hundred ninety-nine LRT samples collected during the 3 weeks following diagnosis yielded virus RNA in 93% of tests. Average (maximum) viral loads were 5 × 10(6) (6 × 10(10)) copies/mL. Viral loads (positive detection frequencies) in 84 URT samples were 1.9 × 10(4) copies/mL (47.6%). Thirty-three percent of all 108 serum samples tested yielded viral RNA. Only 14.6% of stool and 2.4% of urine samples yielded viral RNA. All seroconversions occurred during the first 2 weeks after diagnosis, which corresponds to the second and third week after symptom onset. Immunoglobulin M detection provided no advantage in sensitivity over immunoglobulin G (IgG) detection. All surviving patients, but only slightly more than half of all fatal cases, produced IgG and neutralizing antibodies. The levels of IgG and neutralizing antibodies were weakly and inversely correlated with LRT viral loads. Presence of antibodies did not lead to the elimination of virus from LRT. CONCLUSIONS: The timing and intensity of respiratory viral shedding in patients with MERS closely matches that of those with severe acute respiratory syndrome. Blood viral RNA does not seem to be infectious. Extrapulmonary loci of virus replication seem possible. Neutralizing antibodies do not suffice to clear the infection.