Chloramphenicol treatment revisited - demographics, clinical characteristics, and outcomes of hospitalized patients.

Limited literature exists on chloramphenicol's clinical use. In this retrospective, single-center case-series, we examined 183 chloramphenicol-treated and 81 piperacillin-tazobactam-treated medical patients. Chloramphenicol recipients were older, more debilitated, cognitively impaired, and penicillin allergic, while increased need for inotropics, higher leukocyte count, and higher creatinine levels were notable in the piperacillin-tazobactam group. Pneumonia was the most common indication, with no mortality difference between groups. While acknowledging its antimicrobial activity and potential benefit in specific conditions such as pneumonia, further clinical studies are needed to assess the role of chloramphenicol in the setting where other alternatives are available.

An epidemiological survey of COVID-19 serology and its association with clinical infection among older adults- does antibody titer matter?

BACKGROUND: Older adults are at increased risk of severe SARS-CoV-2 infection. In this study we assessed the response to COVID-19 vaccination and infection rates among nursing homes (NH) and assisted-living care home (ALCH) residents. METHODS: The study was conducted between August 2021 and January 2022, after widespread population vaccination with the third dose of Pfizer-BioNtech mRNA COVID-19 vaccine in Israel. Three groups were addressed: hospitalized older patients; NH and ALCH residents. Demographic data, COVID-19 serology (anti-spike IgG antibodies) and PCR test results were obtained to assess the dynamics of antibody titers and its correlation to infection rates. RESULTS: Two-hundred eighty-five individuals were evaluated; 92 hospitalized patients; 100 ALCH residents and 93 NH residents. In the latter two groups two serology surveys were conducted three months apart. Hospitalized patients were younger than ALCH and NH residents (mean age 80.4 ± 8 versus 82.6 ± 8 and 83.6 ± 5, respectively, p = 0.01), and had more comorbidities (p = 0.003). The degree of decline in the antibody level overtime was similar in ALCH and NH residents. Infection rates were higher among NH residents than ALCH residents [35/91 (38.4%) versus 11/100 (11%), p < 0.001]. Antibody level was lower among those infected [2113 (1271-3512) Au/ml versus 4113 (3364-5029) Au/ml, p < 0.001]. Adjusted analysis showed that NH residence, but not antibody levels, were significantly associated with infection. CONCLUSION: Among older adults, infection rates inversely correlated with antibody level. However, only nursing home residence was significantly associated with infection, suggesting that other factors such as crowding considerably contribute to the risk of infection.

An immune-protein score combining TRAIL, IP-10 and CRP for predicting severe COVID-19 disease.

COVID-19 patients are oftentimes over- or under-treated due to a deficit in predictive management tools. This study reports derivation of an algorithm that integrates the host levels of TRAIL, IP-10, and CRP into a single numeric score that is an early indicator of severe outcome for COVID-19 patients and can identify patients at-risk to deteriorate. 394 COVID-19 patients were eligible; 29% meeting a severe outcome (intensive care unit admission/non-invasive or invasive ventilation/death). The score's area under the receiver operating characteristic curve (AUC) was 0.86, superior to IL-6 (AUC 0.77; p = 0.033) and CRP (AUC 0.78; p < 0.001). Likelihood of severe outcome increased significantly (p < 0.001) with higher scores. The score differentiated severe patients who further deteriorated from those who improved (p = 0.004) and projected 14-day survival probabilities (p < 0.001). The score accurately predicted COVID-19 patients at-risk for severe outcome, and therefore has potential to facilitate timely care escalation and de-escalation and appropriate resource allocation.

Patients with coronavirus disease 2019 characterized by dysregulated levels of membrane and soluble cluster of differentiation 48.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can progress into a severe form of acute lung injury. The cosignaling receptor cluster of differentiation 48 (CD48) exists in membrane-bound (mCD48) and soluble (sCD48) forms and has been reported to be implicated in antiviral immunity and dysregulated in several inflammatory conditions. Therefore, CD48 dysregulation may be a putative feature in COVID-19-associated inflammation that deserves consideration. OBJECTIVE: To analyze CD48 expression in lung autopsies and peripheral blood leukocytes and sera of patients with COVID-19. The expression of the CD48 ligand 2B4 on the membrane of peripheral blood leukocytes was also assessed. METHODS: Twenty-eight lung tissue samples obtained from COVID-19 autopsies were assessed for CD48 expression using gene expression profiling immunohistochemistry (HTG autoimmune panel). Peripheral whole blood was collected from 111 patients with COVID-19, and the expression of mCD48 and of membrane-bound 2B4 was analyzed by flow cytometry. Serum levels of sCD48 were assessed by enzyme-linked immunosorbent assay. RESULTS: Lung tissue of patients with COVID-19 showed increased CD48 messenger RNA expression and infiltration of CD48+ lymphocytes. In the peripheral blood, mCD48 was considerably increased on all evaluated cell types. In addition, sCD48 levels were significantly higher in patients with COVID-19, independently of disease severity. CONCLUSION: Considering the changes of mCD48 and sCD48, a role for CD48 in COVID-19 can be assumed and needs to be further investigated.

Pyogenic Liver Abscess: Contemporary Trends in a Tertiary Institute.

Background: Pyogenic liver abscess (PLA) is an uncommon but potentially life-threatening condition. In recent years, advances in diagnostics and management have led to early diagnosis and treatment and decreased mortality. We present recent data from a large series of patients with PLA and examine the trends in the management of PLA over a period of 50 years. Methods: The medical records of all patients admitted to the Shaare Zedek Medical Center, Israel, between January 2011 and December 2021 with a primary or secondary diagnosis of PLA were reviewed retrospectively. Results: : Ninety-five patients with PLA were identified. Thirty-eight (40%) were female. The median patient age was 66 years (range 18-93). The diagnosis of PLA in all patients was confirmed with abdominal computed tomography (CT). In twenty patients (21.1%), PLA was not diagnosed by the initial abdominal US. Most abscesses were right-sided. Biliary tract origin was the most common underlying cause of PLA (n = 57, 60%), followed by cryptogenic etiology (n = 28, 30%). Escherichia coli, Klebsiella pneumoniae, and Streptococcus species were most commonly identified. The most common primary treatment modality was percutaneous drainage (PD), which was performed in 81 patients (85.3%). Fourteen patients (14.7%) were treated medically without intervention, and two patients (2.1%) were treated surgically following a failure of PD. Four patients died as a direct result of PLA. Conclusions: Patients diagnosed with PLA are older, the male predominance is less pronounced, and the offending pathogens are likely to originate from the biliary tract. This study questions the utility of abdominal US as the initial diagnostic imaging in patients with suspected PLA (versus CT) and demonstrates improved outcomes for patients with PLA over the years.

Rate and Risk Factors for Carbapenem Resistant Acinetobacter baumannii Clinical Infections in Colonized Patients.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important cause of nosocomial infections. Active surveillance for CRAB carriage to identify and isolate colonized patients is used to reduce transmission. OBJECTIVES: To assess the rate and risks of clinical infection among CRAB-carrier and non-carrier patients. METHODS: Hospitalized patients from whom CRAB screening-cultures were obtained between January and June 2018 were identified retrospectively. All CRAB-carriers were compared to a convenient sample of non-carriers and were followed to detect development of CRAB clinical infection during admission. RESULTS: We compared 115 CRAB carriers to 166 non-carriers. The median age in the study group was 76 years (IQR 71-87) vs. 65 years (55-79) in the non-carriers group (P < 0.001). Residence in a nursing facility, debilitated state, and admission to medical wards vs. intensive care units were more frequent among CRAB-carriers (P < 0.001). Mechanically ventilated patients included 51 CRAB carriers (44%) and 102 non-carriers (61%). Clinical infection developed in 49 patients (17%), primarily CRAB pneumonia. Of the CRAB-carriers and non-carriers, 26/115 (23%) and 23/166 (14%), respectively, developed a clinical infection (P = 0.05). One-third of the ventilated patients were infected. Debilitated state and antibiotic treatment during hospitalization were linked to higher infection rates (P = 0.01). Adjusted analysis showed that mechanical ventilation and CRAB colonization were strongly associated with clinical infection (P < 0.05). CONCLUSIONS: The rate of CRAB infection among carriers was high. Mechanical ventilation and CRAB colonization were associated with CRAB clinical infection, primarily pneumonia.

Colistin-resistant Klebsiella pneumoniae bloodstream infection: old drug, bad bug.

Multi-drug-resistant (MDR) Enterobacteriaceae pose a global threat to hospitalized patients. We report a series of colistin-resistant Klebsiella pneumoniae blood isolates from Israel and explore their resistance mechanisms using whole genome sequencing (WGS). Patients with colistin-resistant K. pneumoniae bloodstream infection (BSI) were identified during the period between 2006 and 2018. Demographic and clinical data were collected, and antibiotic susceptibility testing (AST) was performed using three commercial platforms. Long and short read sequencing were performed on a PacBio RS II (Pacific Biosciences) and an Illumina Miseq (Illumina), respectively. Thirteen patients with colistin-resistant K. pneumoniae BSI were identified, and seven isolates from seven different patients were successfully revived. Patient records indicated that five of the patients were previously treated with colistin. AST indicated that six of the seven isolates were colistin resistant and four of these isolates were resistant to carbapenems. WGS assigned the isolates to four distinct clusters that corresponded to in silico-derived multi-locus sequence types (MLST). Three isolates carried blaKPC-3 on two different plasmids and one carried blaOXA-48 on a novel IncL/M plasmid. All colistin-resistant isolates carried a variety of different mutations that inactivated the mgrB gene. We report the first comprehensive analysis of a series of colistin-resistant K. pneumoniae from Israel. A diverse set of isolates were obtained and colistin resistance was found to be attributed to different mechanisms that ablated the mgrB gene. Notably, carbapenemase genes were identified in four isolates and were carried on novel plasmids.

Palindromic rheumatism following COVID-19 infection evolved to rheumatoid arthritis after COVID-19 reinfection.

A 33-year-old woman developed palindromic rheumatism (PLR) several weeks following an infection with severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Three months later, she developed full blown seropositive rheumatoid arthritis (RA) following COVID-19 reinfection. Although the occurrence of the joint diseases and the COVID-19 infections maybe fortuitous, knowing the enormous effects of COVID-19 infection on the human immune system, it is difficult to ignore the temporal relationship between the appearance of PLR after the first COVID-19 infection and the transition to full blown RA following her COVID-19 re-infection.

Anosmia and dysgeusia amongst COVID-19 patients are associated with low levels of serum glucagon-like peptide 1.

PURPOSE: Anosmia and dysgeusia (AD) are common amongst COVID-19 patients. These symptoms are not frequently associated with rhinorrhea or nasal congestion and the underlying mechanism is unclear. Previous reports suggested that glucagon-like peptide-1 (GLP-1) signalling plays a role in the modulation of olfaction and ageusia. We aimed to assess the correlation between GLP-1 and COVID-19-associated AD. METHODS: Blood samples obtained from COVID-19 patients with and without AD were tested for serum GLP-1 levels using enzyme-linked immunosorbent assay (ELISA). A second control group comprised of COVID-19-negative volunteers. RESULTS: Forty-nine subjects were included in the study. Nineteen were positive for COVID-19. Of the 19 patients, 10 had AD and 9 declined such complaints. Age and basic metabolic rate were similar amongst all study groups. Serum GLP-1 levels were significantly lower amongst patients with AD compared with patients without AD and COVID-19-negative individuals (1820 pg/mL vs 3536 pg/mL vs 3014 pg/mL, respectively, P < .02). CONCLUSION: COVID-19 patients who reported AD had lower serum levels of GLP-1 compared with those lacking AD symptoms and COVID-19-negative individuals. These results suggest that GLP-1 may be involved in the pathogenesis of AD. However, further larger scale studies should corroborate our findings.

QTc prolongation among hydroxychloroquine sulphate-treated COVID-19 patients: An observational study.

BACKGROUND: The liberal administration of hydroxychloroquine-sulphate (HCQ) to COVID-19 patients has raised concern regarding the risk of QTc prolongation and cardiac arrhythmias, particularly when prescribed with azithromycin. We evaluated the incidence of QTc prolongation among moderately and severely ill COVID-19 patients treated with HCQ and of the existence of concomitant alternative causes. METHODS: All COVID-19 patients treated with HCQ (between Mar 1 and Apr 14, 2020) in a tertiary medical centre were included. Clinical characteristics and relevant risk factors were collected from the electronic medical records. Individual patient QTc intervals were determined before and after treatment with HCQ. The primary outcome measure sought was a composite end point comprised of either an increase ≥60 milliseconds (ms) in the QTc interval compared with pre-treatment QTc, and/or a maximal QTc interval >500 ms RESULTS: Ninety patients were included. Median age was 65 years (IQR 55-75) and 57 (63%) were male. Thirty-nine patients (43%) were severely or critically ill. Hypertension and obesity were common (n = 23 each, 26%). QTc prolongation evolved in 14 patients (16%). Age >65 years, congestive heart failure, severity of disease, C-reactive protein level, hypokalaemia and furosemide treatment, were all associated with QTc prolongation. Adjusted analysis showed that QTc prolongation was five times more likely with hypokalaemia [OR 5, (95% CI, 1.3-20)], and three times more likely with furosemide treatment [OR 3 (95% CI, 1.01-13.7)]. CONCLUSION: In patients treated with HCQ, QTc prolongation was associated with the presence of traditional risk factors such as hypokalaemia and furosemide treatment.

Modification of Blood Test Draw Order to Reduce Blood Culture Contamination: A Randomized Clinical Trial.

BACKGROUND: Blood culture contamination leads to unnecessary interventions and costs. It may be caused by bacteria in deep skin structures unsusceptible to surface decontamination. This study was designed to test whether diversion of blood obtained at venipuncture into a lithium heparin tube prior to aspiration of blood culture reduces contamination. METHODS: The order of blood draws for biochemistry and blood cultures was randomized. Following standard disinfection and venipuncture, blood was either aspirated into a sterile lithium heparin tube before blood culture bottles (diversion group) or blood cultures first and then lithium heparin tube (control group). All study personnel were blinded with the exception of the phlebotomist. RESULTS: After exclusions, 970 blood culture/biochemistry sets were analyzed. Contamination occurred in 24 of 480 (5.0%) control vs 10 of 490 (2.0%) diversion group cultures (P = .01). True pathogens were identified in 26 of 480 (5.4%) control vs 18 of 490 (3.7%) diversion cultures (P = .22). Despite randomization, demographic differences were apparent between the 2 groups. A post hoc analysis of 637 cultures from 610 medical patients admitted from home neutralized demographic differences. Culture contamination remained more frequent in the control vs diversion group (17/312 [5%] vs 7/325 [2%]; P = .03). Fewer diversion group patients were admitted to hospital (control: 200/299 [66.9%] vs diversion: 182/311 [58.5%]; P = .03), and length of stay was shorter (control: 30 hours [interquartile range {IQR}, 6-122] vs diversion: 22 [IQR, 5-97]; P = .02). CONCLUSIONS: Use of lithium heparin tubes for diversion prior to obtaining blood cultures led to a 60% decrease in contamination. This technique is easy and inexpensive and might decrease overall hospital length of stay. CLINICAL TRIALS REGISTRATION: NCT03966534.

Mucormycosis in the Middle East and North Africa: Analysis of the FungiScope® registry and cases from the literature.

BACKGROUND: Regional differences in the underlying causes, manifestations and treatment of mucormycosis have been noted in studies covering Europe, Asia and South America. OBJECTIVES: To review cases of mucormycosis across the Middle East and North Africa (MENA) region in order to identify epidemiological, treatment and outcome trends in this region. PATIENTS/METHODS: Cases of proven or probable invasive mucormycosis from the region were identified from the FungiScope® database and the medical literature. For each case, information on underlying condition, site of infection, pathogenic species, therapeutic intervention, type of antifungal therapy and outcome were analysed. RESULTS: We identified 310 cases of mucormycosis in the MENA region. The number of reported cases increased by decade from 23 before 1990 to 127 in the 2010s. In this region, the most common underlying conditions associated with mucormycosis were diabetes mellitus (49.7%) and conditions associated with immunosuppression (46.5%). The majority of patients received treatment with antifungals (93.5%), with a large proportion treated with both antifungals and surgery (70.6%). Overall mortality rates decreased from 47.8% before 1990 to 32.3% in the 2010s. CONCLUSIONS: The number of reported cases of mucormycosis in the MENA region has risen over the past few decades, in line with increases in the number of patients with underlying conditions associated with this infection. Although the majority of patients received treatment with antifungal therapies and/or surgery, the associated mortality rate remains high and there is a clear need for more effective prevention and treatment strategies in the MENA region.

Intensive Care Admissions and Associated Severity of Influenza B Versus A During Influenza B Vaccine-mismatched Seasons.

Patients admitted to hospital with influenza B and A in Jerusalem, Israel, during the 2015-2016 and 2017-2018 influenza seasons demonstrated similar rates of intensive care unit (ICU) admission and associated disease severity. Most (63%) influenza B ICU patients received influenza B-mismatched trivalent vaccine. These findings call into question the equivalence of trivalent and quadrivalent vaccines in preventing severe influenza B.

An intervention to control an ICU outbreak of carbapenem-resistant Acinetobacter baumannii: long-term impact for the ICU and hospital.

BACKGROUND: Following a fatal intensive care unit (ICU) outbreak of carbapenem-resistant Acinetobacter baumanii (CRAB) in 2015, an aggressive infection control intervention was instituted. We outline the intervention and long-term changes in the incidence and prevalence of CRAB. METHODS: The infection control intervention included unit closure (3 days), environmental cleaning, hand hygiene interventions, and environmental culturing. CRAB acquisition and prevalence and colistin use were compared for the 1 year before and 2 years after the intervention. RESULTS: Following the intervention, ICU CRAB acquisition decreased significantly from 54.6 (preintervention) to 1.9 (year 1) to 5.6 cases (year 2)/1000 admissions (p < 0.01 for comparisons with preintervention period.). Unexpectedly, ICU CRAB admission prevalence also decreased from 56.5 to 5.8 to 13 cases/1000 admissions (p < 0.001) despite the infection control intervention's being directed at the ICU alone. In parallel, hospital CRAB prevalence decreased from 4.4 to 2.4 to 2.5 cases/1000 admissions (p < 0.001), possibly as a result of decreased discharge of CRAB carriers from the ICU to the wards (58.5 to 1.9 to 7.4 cases/1000 admissions; p < 0.001). ICU colistin consumption decreased from 200 to 132 to 75 defined daily dose (DDD)/1000 patient-days (p < 0.05). Hospital colistin consumption decreased from 21.2 to 19.4 to 14.1 DDD/1000 patient-days (p < 0.05). CONCLUSIONS: The ICU infection control intervention was highly effective, long-lasting, and associated with a decrease in last-line antibiotic use. The intervention was associated with the unexpected finding that hospital CRAB prevalence also decreased.

[AN EDUCATIONAL INTERVENTION TO REDUCE THE RATE OF CONTAMINANTS IN BLOOD CULTURES AND IMPROVE APPROPRIATE ANTIBIOTIC TREATMENT].

INTRODUCTION: Blood cultures' contamination (BCC) is associated with unnecessary processing of cultures, higher cost, and occasionally, unjustified antibiotic treatment. We aimed to reduce the rate of BCC by educational intervention. In parallel, we also strove to expand the use of aminoglycosides (AMG) and reduce the utilization of beta-lactam antibiotics. The rate of BCC was assessed prospectively in the study department - the Emergency Department (ED) and in control departments - Medical Departments A, B and Geriatrics. Data was collected continuously during the study period and educational interventions were performed in the ED but not in the control departments. The intervention included meetings with ED staff, emphasizing proper blood culture collection technique, and post-intervention result updates. The utilization of AMG was encouraged in cases of suspected gram-negative bacteremia. The empirical and definitive antibiotic regimen was assessed. During the study period, a 30% decrease in BCC rate [33/564 (5.9%) to 30/734 (4.1%), p=0.143] was noted in the study department whereas a small increase in BCC rate was noted in the control departments. Logistic regression analysis revealed significantly different trends in BCC rate between the study and control departments (p<0.001). Additionally, an increase in AMG utilization was observed (7% to 40%) in patients with suspected gram-negative bacteremia with normal renal function (p=0.16). Educational intervention was successful in reducing the rate of BCC and in parallel, increasing the utilization of AMG. Repeat and frequent interventions are required to maintain such achievements.