COVID-19 Compared to Other Pandemic Diseases.

In December 2019, the first cases of a new contagious disease were diagnosed in the city of Wuhan, the capital of Hubei province in China. Within a short period of time the outbreak developed exponentially into a pandemic that infected millions of people, with a global death toll of more than 500,000 during its first 6 months. Eventually, the novel disease was named coronavirus disease 2019 (COVID-19), and the new virus was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Similar to all known pandemics throughout history, COVID-19 has been accompanied by a large degree of fear, anxiety, uncertainty, and economic disaster worldwide. Despite multiple publications and increasing knowledge regarding the biological secrets of SARS-CoV-2, as of the writing of this paper, there is neither an approved vaccine nor medication to prevent infection or cure for this highly infectious disease. Past pandemics were caused by a wide range of microbes, primarily viruses, but also bacteria. Characteristically, a significant proportion of them originated in different animal species (zoonoses). Since an understanding of the microbial cause of these diseases was unveiled relatively late in human history, past pandemics were often attributed to strange causes including punishment from God, demonic activity, or volatile unspecified substances. Although a high case fatality ratio was common to all pandemic diseases, some striking clinical characteristics of each disease allowed contemporaneous people to clinically diagnose the infection despite null microbiological information. In comparison to past pandemics, SARS-CoV-2 has tricky and complex mechanisms that have facilitated its rapid and catastrophic spread worldwide.

How holobionts get sick-toward a unifying scheme of disease.

All humans, animals, and plants are holobionts. Holobionts comprise the host and a myriad of interacting microorganisms-the microbiota. The hologenome encompasses the genome of the host plus the composite of all microbial genomes (the microbiome). In health, there is a fine-tuned and resilient equilibrium within the members of the microbiota and between them and the host. This relative stability is maintained by a high level of microbial diversity, a delicate bio-geographic distribution of microorganisms, and a sophisticated and intricate molecular crosstalk among the multiple components of the holobiont. Pathobionts are temporarily benign microbes with the potential, under modified ecosystem conditions, to become key players in disease. Pathobionts may be endogenous, living for prolonged periods of time inside or on the host, or exogenous, invading the host during opportunistic situations. In both cases, the end result is the transformation of the beneficial microbiome into a health-perturbing pathobiome. We hypothesize that probably all diseases of holobionts, acute or chronic, infectious or non-infectious, and regional or systemic, are characterized by a perturbation of the healthy microbiome into a diseased pathobiome.

Unusual "flesh-eating" strains of Escherichia coli.

Monomicrobial necrotizing fasciitis (type II) is typically caused by group A streptococcus alone or in combination with Staphylococcus aureus. Escherichia coli has been isolated from polymicrobial or Fournier's gangrene but has rarely been reported in monomicrobial necrotizing fasciitis. We describe the clinical characteristics and outcomes of seven cases of monomicrobial E. coli necrotizing fasciitis and/or severe soft tissue infection diagnosed at a single institution during an 18-month period. Four isolates from three patients and two isolates from two patients with type I polymicrobial severe soft tissue infection (controls) were assayed by the randomly amplified polymorphic DNA (RAPD) analysis for fingerprinting and PCR amplification of primers in order to detect cytotoxic necrotizing factor 1 and 2 (cnf1 and cnf2) genes. All patients had some type of immune suppression. The limb was the most commonly involved organ. In all cases, E. coli was isolated as a monomicrobial pathogen from blood, fascia, or both. All patients died during hospitalization, three within the first 48 h. The RAPD amplification assay showed a high degree of genetic diversity among the "flesh-eating" strains and controls. The cnf1 toxin gene was identified in two out of three cases, but not in the controls. cnf2 was not detected in any of the patients. E. coli may be responsible for life-threatening necrotizing fasciitis. Further research is needed to reveal relevant risk factors, reservoirs, and modes of transmission of cnf1 E. coli.

Positron emission tomography/computed tomography for the diagnosis of endocarditis in patients with pulmonic stented valve/pulmonic stent.

Percutaneous pulmonic valve and pulmonic stent implantation have become a well-established treatment for recurrent pulmonic stenosis or insufficiency in patients with repaired congenital heart disease. Late endocarditis is seldom reported, but its diagnosis might be challenging due to the limited visualization of the stented valve or stent by transesophageal echocardiography. We present 2 young patients who were hospitalized for suspected endocarditis and in whom the diagnosis was made with the aid of positron emission tomography/computed tomography scan.

A large Q fever outbreak in an urban school in central Israel.

BACKGROUND. On 28 June 2005, numerous cases of febrile illness were reported among 322 students and employees of a boarding high school located in an urban area in central Israel. Subsequent investigation identified a large outbreak of Q fever which started 2 weeks earlier. We describe the investigation of this outbreak and its possible implications. METHODS. We conducted a case-control study to identify risk factors for Q fever disease. Environmental sampling was conducted to identify the source and the mode of transmission of Coxiella burnetii, the infectious agent. RESULTS. Of 303 individuals, 187 (62%) reported being ill between 15 June and 13 July 2005. Serological evidence for C. burnetii infection was evident in 144 (88%) of the 164 tested individuals. Being a student, dining regularly at the school dining room, and boarding at school during a June religious holiday and the preceding weekend were all significant risk factors for contracting Q fever. C. burnetii DNA was detected using polymerase chain reaction on samples from the school dining room's air conditioning system, supporting contribution of the air conditioning system to the aerosol transmission of the infectious agent. CONCLUSIONS. We report a large outbreak of Q fever in an urban school, possibly transmitted through an air conditioning system. A high level of suspicion for C. burnetii infection should be maintained when investigating point source outbreaks of influenza-like disease, especially outside the influenza season.

Travel-related leptospirosis in Israel: a nationwide study.

Leptospirosis is re-emerging in developed countries as a travel-related infection. In this nationwide study of travel-related leptospirosis in Israel, all cases diagnosed at the Central Reference Laboratory for Leptospirosis, during 2002-2008 were retrospectively reviewed and only travel-related cases were included. During the study years, 20 (42%) of 48 leptospirosis cases in Israel were travel-related. Exposure occurred in Southeast Asia in 15 (75%) of 20 cases. The estimated yearly incidence of travel-related leptospirosis was 1.78/100,000 travelers compared with an incidence of endemic cases of 0.06/100,000 inhabitants (risk ratio = 29.6, 95% confidence interval = 16.7-52.4). Most patients (89%) were infected during water-related activities. Severe disease was present in 10 (55%) of 18 patients; 7 of them were presumptively infected with the Icterohaemorrhagiae serogroup. Thus, travel-related leptospirosis is becoming increasingly important in the epidemiology of leptospirosis in Israel. Leptospirosis should be suspected in any traveler with undifferentiated febrile illness, especially when water exposure is reported.

Adult-onset ornithine transcarbamylase (OTC) deficiency unmasked by the Atkins' diet.

BACKGROUND & AIMS: Late-onset symptoms of urea-cycle disorder may lead to a life-threatening disease which is often undetected. We report the clinical and metabolic manifestations of acute hyperammonemic encephalopathy in a 47-year-old asymptomatic man with ornithine transcarbamylase (OTC) deficiency. The hyperammonemic encephalopathy was unmasked by a high-protein Atkins diet. METHODS: Genetic analysis of the patient's family, 89 unrelated Ashkenazi Jewish and 50 unrelated Europeans subjects was performed using polymerase chain reaction amplification and DNA sequencing of the OTC gene. RESULTS: Treatment with hemodialysis, provision of adequate calories to prevent catabolism, and protein elimination for 24h followed by protein restriction and ammonia scavenging medications effectively lowered the patient's plasma ammonia level and resulted in full recovery. Genetic analysis of the OTC gene revealed a novel hemizygous missense mutation in exon 5 (c.477T>G), leading to an isoleucine-to-methionine substitution in codon 159 (Ile159Met). Further genetic analysis of the patient's family yielded the mutation in many of them, although findings were negative in 89 unrelated Ashkenazi Jewish and 50 unrelated Europeans subjects. CONCLUSIONS: This is the first reported case of an adult urea-cycle defect unmasked by the Atkins diet. Measurements of serum ammonia level must be part of the basic work-up in all patients presenting with encephalopathy of unknown origin even in the absence of liver dysfunction. Awareness of this important association can contribute to prompt diagnosis and life-saving treatment. Correct diagnosis is also important to prevent future recurrences and to provide genetic counselling for family members.

Pericarditis as a presenting sign of infective endocarditis: two case reports and review of the literature.

Pericarditis as a presenting sign of infective endocarditis is rare. Here we describe 2 cases and an additional 19 cases of pericarditis as a presenting sign of infective endocarditis reported during the last 40 y. 71% of patients were young males (mean age 43.2 y). The most commonly reported underlying conditions were diabetes mellitus type 2 (5 patients, 24%), and substance or alcohol abuse (4 patients, 19%). The native aortic valve was the most frequently involved valve. The most common symptoms were fever, cough or dyspnoea, and chest pain. Overt tamponade was diagnosed in 47% of the patients. However, pulsus paradoxus and pericardial friction rub were rare. A heart murmur was heard in 12 patients (57%). Staphylococcus aureus was the most commonly isolated pathogen concomitantly from blood and pericardial fluid. 16 patients (76%) were operated. Six underwent a pericardial procedure, 5 underwent valve replacement, 4 both, and 1 patient was operated for pseudoaneurysm. Mortality rates were 60% and 31% of patients treated with antibiotics alone versus antibiotics and surgical intervention, respectively. In patients presenting with pericarditis with or without cardiac tamponade, the possibility of infective endocarditis should be considered. Optimal therapy should consist of antibiotics and surgical intervention.

Clinical and radiological features of Mycobacterium kansasii infection and Mycobacterium simiae infection.

This retrospective study sought to systematically identify clinical and radiological features of Mycobacterium kansasii and Mycobacterium simiae infections. The sample included consecutive patients with a culture-positive diagnosis of M. simiae infection (n=102) or M. kansasii infection (n=62) derived from the databases of the Laboratory of Microbiology of a tertiary medical centre and two outpatient tuberculosis centres. Data on patient background and clinical features were collected, and chest radiographs were analysed. Sixty percent of the M. kansasii group were native born compared to 18% of the M. simiae group (p=0.0001). M. simiae infection was associated with a higher rate of co-morbid disease, including diabetes mellitus, heart disease, and malignancy. A similar rate of lung disease was found in both groups. Clinical symptoms were significantly more common in patients with M. kansasii infection. On radiological study, M. kansasii infection was associated with more cavitations, and M. simiae infection with more pulmonary infiltrates. Patients with M. simiae infection had a higher likelihood of middle and lower lobe disease whereas patients with M. kansasii infection had more upper lobe disease (p=0.001). Pleural effusions and lymphadenopathy were found only in the presence of M. simiae infection. We concluded that there are major differences in the epidemiologic features of M. kansasii and M. simiae infection which have important diagnostic and therapeutic implications.

Treatment of human brucellosis: systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: To determine and quantify differences in efficacy between treatment regimens for brucellosis. DESIGN: Systematic review and meta-analysis of randomised controlled trials assessing different antibiotic regimens and durations of treatment for human brucellosis. DATA SOURCES: PubMed, CENTRAL, Lilacs, conference proceedings, and bibliographies with no restrictions on language, study year, or publication status. Review methods Search, application of inclusion and exclusion criteria, data extraction, and assessment of methodological quality independently performed in duplicate. Primary outcomes were relapse and overall failure resulting from primary failure or relapse. Relative risks with 95% confidence intervals were calculated and pooled with a fixed effect model. RESULTS: 30 trials and 77 treatment arms were included. Overall failure was significantly higher with doxycycline-rifampicin compared to doxycycline-streptomycin, mainly due to a higher rate of relapse (relative risk 2.80, 95% confidence interval 1.81 to 4.36; 13 trials, without heterogeneity). Results were consistent among patients with bacteraemia and complicated brucellosis. Doxycycline-streptomycin resulted in a significantly higher rate of failure than doxycycline-rifampicin-aminoglycoside (triple drug regimen) (2.50, 1.26 to 5.00; two trials). Gentamicin was not inferior to streptomycin (1.45, 0.52 to 4.00 for failure; two trials). Quinolones combined with rifampicin were significantly less effective than doxycycline combined with rifampicin or streptomycin (1.83, 1.11 to 3.02, for failure; five trials). Monotherapy was associated with a higher risk of failure than combined treatment when administered for a similar duration (2.56, 1.55 to 4.23; five trials). Treatment for six weeks or more offered an advantage over shorter treatment durations. CONCLUSIONS: There are significant differences in effectiveness between currently recommended treatment regimens for brucellosis. The preferred treatment should be with dual or triple regimens including an aminoglycoside.

Pleural plaques related to "take-home" exposure to asbestos: An international case series.

CONTEXT: While a large number of studies indicate the risks of high-level exposures to asbestos in the workplace setting, a relatively small number of studies describe the risk of pleural disease related to "take-home" asbestos brought into the household by workers exposed to asbestos. Consequently, the risk of pleural disease in family members of asbestos-exposed workers is likely underappreciated. CASE PRESENTATIONS: Two families of siblings, one in Israel and one in the US, were evaluated because of their significant exposures to asbestos brought into the home by family members with heavy occupational exposures. Two of the four children of an asbestos cement debagger in Petach Tikvah, Israel and two children of a pipe lagger in a naval shipyard near Seattle, Washington, manifested benign pleural disease without parenchymal disease, despite having no occupational exposure to asbestos. DISCUSSION: These cases illustrate that "take-home" asbestos exposure may lead to pleural disease at higher rates than commonly realized. RELEVANCE TO CLINICAL PRACTICE: Providers should recognize that due to the potential for "take-home" exposures, asbestos-related disease in a patient may be a marker for disease in household contacts. Patients with family members heavily exposed to asbestos should be strongly encouraged to quit smoking in an effort to reduce any further carcinogenic exposures. Additionally, workplace control and regulation of asbestos use should be emphasized to protect both workers and their families.

The epidemiology of bacteremia with febrile neutropenia: experience from a single center, 1988-2004.

BACKGROUND: The epidemiology of bacteremic febrile neutropenia differs between locations and constitutes the basis for selection of empiric antibiotic therapy for febrile neutropenia. OBJECTIVES: To describe the epidemiology of bacteremia among patients with neutropenia in a single center in Israel. METHODS: We conducted a prospective data collection on all patients with neutropenia (< 500/mm3) and clinically significant bacteremia or fungemia during the period 1988-2004. RESULTS: Among adults (462 episodes) the most common bloodstream isolate was Escherichia coli. Gram-negative bacteria predominated throughout the study period and the ratio between Gram-negative and Gram-positive bacteremia increased from 1.7 to 2.3. Among children (752 episodes), the ratio between Gram-negative and Gram-positive bacteremia reversed from 1.2 to 0.7, due to increasing prevalence of coagulase-negative staphylcoccal bacteremia. Both among adults and children, the length of hospital stay prior to bacteremia had a major impact on the pathogens causing bacteremia and their antibiotic susceptibilities. The prevalence of E. coli decreased with time in hospital, while the rates of Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter spp., Acinetobacter spp., Enterococcus spp. and Candida spp. increased. Resistance to broad-spectrum empiric monotherapy in our center was observed in > 40% of Gram-negative bacteria when bacteremia was acquired after 14 days in hospital. CONCLUSIONS: Improved infection-control measures for neutropenic cancer patients in our center are needed. Empiric antibiotic treatment should be tailored to patients' risk for multidrug-resistant organisms. Individual hospitals should monitor infection epidemiology among cancer patients to guide empiric antibiotic treatment.

Appropriateness of antibiotic therapy on weekends versus weekdays.

OBJECTIVES: To compare the appropriateness of antibiotic treatment prescribed in an emergency department (ED) of a tertiary medical centre on weekdays and weekends. METHODS: During a 1 month period, medical charts of 1029 ED visits for patients who were discharged from the ED were reviewed. Data of patients who were discharged with antibiotics were blind evaluated by two infectious disease specialists, and an 'appropriateness score' was given to the antibiotic prescription. RESULTS: Antibiotics were prescribed at discharge for 182 (17.7%) patients. Appropriate antibiotic treatment was administered significantly less frequently on weekends when compared with weekdays (P = 0.004). Appropriateness scores were higher for the surgical and urological wings (P = 0.011) and for diagnoses of pneumonia and urinary tract infection (P = 0.005). Time of the day and patient's age and sex did not have a significant effect on the appropriateness score. Adjusting for all variables, only weekends remained significantly associated with less appropriate antibiotic treatment, odds ratio 0.35 and 95% confidence intervals 0.16-0.78. CONCLUSIONS: This study shows less appropriate antibiotic prescription in an ED on weekends than weekdays. More studies are required to clarify measures to improve appropriate antibiotic therapy at weekends.

Predicting Clostridium difficile toxin in hospitalized patients with antibiotic-associated diarrhea.

OBJECTIVE: Clostridium difficile infection is implicated in 20%-30% of cases of antibiotic-associated diarrhea. Studying hospitalized patients who received antibiotic therapy and developed diarrhea, our objective was to compare the clinical characteristics of patients who developed C. difficile-associated diarrhea (CDAD) with those of patients with a negative result of a stool assay for C. difficile toxin. METHODS: A prospective study was done with a cohort of 217 hospitalized patients who had received antibiotics and developed diarrhea. Patients with CDAD were defined as patients who had diarrhea and a positive result for C. difficile toxin A/B by an enzyme immunoassay of stool. The variables that yielded a significant difference on univariate analysis between patients with a positive assay result and patients with a negative assay result were entered into a logistic regression model for prediction of C. difficile toxin.Setting. A 900-bed tertiary care medical center. RESULTS: Of 217 patients, 52 (24%) had a positive result of assay for C. difficile toxin A/B in their stool. The logistic regression model included impaired functional capacity, watery diarrhea, use of a proton pump inhibitor, use of a histamine receptor blocker, leukocytosis, and hypoalbuminemia. The area under the receiver operating characteristic curve for the model as a predictor of a positive result for the stool toxin assay was 0.896 (95% confidence interval, 0.661-1.000; P<.001), with 95% specificity and 68% sensitivity. CONCLUSIONS: Our results may help clinicians to predict the risk of CDAD in hospitalized patients with antibiotic-associated diarrhea, to guide careful, specific empirical therapy, and to direct early attention to infection control issues.

Successful organ transplantation from donors with Acinetobacter baumannii septic shock.

Donor bacteremia with severe sepsis, especially due to gram-negative organisms, has been considered a contraindication to transplantation. Over a 6-month period we prospectively collected standardized data on all brain-dead, heart-beating organ donors with gram negative bacteremia and septic shock and the recipients of their organs in hospitals throughout Israel. Donors were treated with appropriate antibiotics for at least 48 hr prior to organ retrieval while recipients received 7 days of culture-specific antibiotics following transplantation. In total, 12 organs were transplanted (5 kidneys, 2 livers, 3 lungs and 2 hearts) from 3 donors with Acinetobacter baumannii bacteremia and septic shock. All patients were alive with good graft function 60 days following transplantation, apart from one of the heart recipients who died of primary nonfunction on the second postoperative day. Two recipients developed postoperative infections, none with Acinetobacter sp. (one Pseudomonas sp. urinary tract infection, one Klebsiella sp. central venous catheter sepsis).

Emergence of Mycobacterium simiae in respiratory specimens.

Temporal changes in epidemiology of non-tuberculous mycobacteria (NTM) infections have hardly been explored. Frequency of isolation of different NTM species varies geographically. We aimed to determine whether the distribution of Mycobacteria species isolated from respiratory specimens had changed from 1996 to 2003. We analysed data on 484 patient mycobacterial isolates from 23,483 respiratory specimens submitted to the Laboratory of Microbiology in a tertiary medical centre. The proportion of patients with Mycobacterium tuberculosis isolates decreased from 44.6% in period I (1996-1999) to 20.6% in period II (2000-2003). Among the NTM, the proportion of some species increased significantly (Mycobacterium simiae: 8.4% to 31.6%; Mycobacterium fortuitum 12% to 20%; and Mycobacterium chelonae 4.8% to 11.3%), while others decreased (Mycobacterium avium complex 31.3% to 17.3%; Mycobacterium kansasii 28.9% to 7.5%; and Mycobacterium haemophilum 1.2% to 0%). These findings disclose major temporal changes in the distribution of mycobacterial species in respiratory specimens with an impressive emergence and takeover of M. simiae.

Malaria in travelers returning from short organized tours to holiday resorts in Mombassa, Kenya.

BACKGROUND: Short trips to holiday resorts in Mombassa, Kenya, have gained popularity among Israelis since the early 1990s. A cluster of cases of malaria among returned travelers raised concern that preventive measures were being neglected. OBJECTIVES: To characterize the demographic and clinical features of malaria acquired in Kenya, and to assess the adequacy of preventive measures. METHODS: Data were collected from investigation forms at the Ministry of Health. All persons who acquired malaria in Kenya during the years 1999-2001 were contacted by phone and questioned about use of chemoprophylaxis, attitudes towards malaria prevention, and disease course. Further information was extracted from hospital records. RESULTS: Kenya accounted for 30 (18%) of 169 cases of malaria imported to Israel and was the leading source of malaria in the study period. Of 30 malaria cases imported from Kenya, 29 occurred after short (1-2 weeks) travel to holiday resorts in Mombassa. Average patient age was 43 +/- 12 years, which is older than average for travelers to tropical countries. Only 10% of the patients were fully compliant with malaria chemoprophylaxis. The most common reason for non-compliance was the belief that a short trip to a holiday resort carries a negligible risk of malaria. Only 3 of 13 patients (23%) who consulted their primary physician about post-travel fever were correctly diagnosed with malaria. Twenty percent of cases were severe enough to warrant admission to an intensive care unit; one case was fatal. CONCLUSIONS: Measures aimed at preventing malaria and its severe sequelae among travelers should concentrate on increasing awareness of risks and compliance with malaria chemoprophylaxis.

Antibacterial susceptibility of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli.

BACKGROUND: The prevalence of extended-spectrum beta-lactamase-producing organisms and their antimicrobial resistance patterns may vary between geographic areas. OBJECTIVES: To evaluate the prevalence and susceptibility of ESBL-producing organisms among Klebsiella pneumoniae and Escherichia coli isolated from adult and pediatric patients in two Israeli hospitals. METHODS: ESBL production was tested according to recommendations of the Clinical and Laboratory Standards Institute, using ceftazidime (30 microg) and a combination of ceftazidime/clavulanate (30/ 10 microg) disks with a > or =5 mm difference indicating positivity. Antibiotic susceptibilities were determined by the disk diffusion method according to CLSI standards. Minimal inhibitory concentrations were determined by the E-test. RESULTS: The prevalence of ESBL-producing organisms was significantly higher among K. pneumoniae than E. coli isolates - 32% (241/765) vs. 10% (57/547) respectively (P < 0.001), and more frequently isolated from adults than children (odds ratio 2.27 for K. pneumoniae and 12.94 for E. coli). Resistance rates for amoxicillin/ clavulanate, piperacillin-tazobactam, amikacin, and ciprofloxacin among the ESBL-producing K. pneumoniae and E. coli isolates were 95%, 82%, 49% and 77% for K. pneumoniae, and 77%, 35%, 25% and 100% for E coli. Two (0.8%) ESBL-producing and 4 (0.7%) ESBL-negative K. pneumoniae isolates showed intermediate susceptibility (MIC 6 microg/ml) to meropenem. All isolates were sensitive to ertapenem and colistin. CONCLUSION: ESBL production among K. pneumoniae and E. coli is more prevalent in the adult population than the pediatric population and is associated with multidrug resistance.