No SARS-CoV-2 detection in the German CAPNETZ cohort of community acquired pneumonia before COVID-19 peak in March 2020.

PURPOSE: The first SARS-CoV-2 cases in Europe were reported in January 2020. Recently, concern arose on unrecognized infections before this date. For a better understanding of the pandemic, we retrospectively analyzed patient samples for SARS-CoV-2 from the prospective CAPNETZ study cohort. METHODS: We used nasopharyngeal swab samples from a cohort of well characterized patients with community acquired pneumonia of the CAPNETZ study group, recruited from different geographic regions across Germany, Austria, the Netherlands, and Switzerland between 02nd December 2019 and 28th April 2020. Multiplex real-time RT-PCR for a broad range of respiratory pathogens and SARS-CoV-2 real-time RT-PCR were performed on all samples. RESULTS: In our cohort, respiratory pathogens other than SARS-CoV-2 were detected in 21.5% (42/195) of patients with rhinovirus as the most frequently detected pathogen. The detection rate increased to 29.7% (58/195) when SARS-CoV-2 was included. No SARS-CoV-2 positive sample was detected before end of March 2020. CONCLUSIONS: Respiratory viral pathogens accounted for a considerable number of positive results but no SARS-CoV-2 case was identified before the end of March 2020.

Epidemiology and Molecular Identification and Characterization of Mycoplasma pneumoniae, South Africa, 2012-2015.

During 2012-2015, we tested respiratory specimens from patients with severe respiratory illness (SRI), patients with influenza-like illness (ILI), and controls in South Africa by real-time PCR for Mycoplasma pneumoniae, followed by culture and molecular characterization of positive samples. M. pneumoniae prevalence was 1.6% among SRI patients, 0.7% among ILI patients, and 0.2% among controls (p<0.001). Age <5 years (adjusted odd ratio 7.1; 95% CI 1.7-28.7) and HIV infection (adjusted odds ratio 23.8; 95% CI 4.1-138.2) among M. pneumonia-positive persons were associated with severe disease. The detection rate attributable to illness was 93.9% (95% CI 74.4%-98.5%) in SRI patients and 80.7% (95% CI 16.7%-95.6%) in ILI patients. The hospitalization rate was 28 cases/100,000 population. We observed the macrolide-susceptible M. pneumoniae genotype in all cases and found P1 types 1, 2, and a type 2 variant with multilocus variable number tandem repeat types 3/6/6/2, 3/5/6/2, and 4/5/7/2.

Increased Community-Associated Infections Caused by Panton-Valentine Leukocidin-Negative MRSA, Shanghai, 2005-2014.

During 2005-2014, community-associated methicillin-resistant Staphylococcus aureus infections increased in Shanghai, China. Most infections were caused by sequence type 59 S. aureus that lacked Panton-Valentine leukocidin. This finding challenges the notion that Panton-Valentine leukocidin is necessary for epidemiologic success of community-associated methicillin-resistant S. aureus.

Travel- and Community-Based Transmission of Multidrug-Resistant Shigella sonnei Lineage among International Orthodox Jewish Communities.

Shigellae are sensitive indicator species for studying trends in the international transmission of antimicrobial-resistant Enterobacteriaceae. Orthodox Jewish communities (OJCs) are a known risk group for shigellosis; Shigella sonnei is cyclically epidemic in OJCs in Israel, and sporadic outbreaks occur in OJCs elsewhere. We generated whole-genome sequences for 437 isolates of S. sonnei from OJCs and non-OJCs collected over 22 years in Europe (the United Kingdom, France, and Belgium), the United States, Canada, and Israel and analyzed these within a known global genomic context. Through phylogenetic and genomic analysis, we showed that strains from outbreaks in OJCs outside of Israel are distinct from strains in the general population and relate to a single multidrug-resistant sublineage of S. sonnei that prevails in Israel. Further Bayesian phylogenetic analysis showed that this strain emerged approximately 30 years ago, demonstrating the speed at which antimicrobial drug-resistant pathogens can spread widely through geographically dispersed, but internationally connected, communities.

Betamethasone and dexamethasone in adult community-acquired bacterial meningitis: a quality registry study from 1995 to 2014.

Acute bacterial meningitis (ABM) is a highly lethal disease. Available data support the use of corticosteroids in high-income countries, but the effect on mortality is still controversial. The effects of corticosteroids on mortality and sequelae were evaluated in the national Swedish quality registry. In total, during 1995-2014 1746 adults with ABM were included, of whom 989 were treated with corticosteroids (betamethasone, n = 766; dexamethasone, n = 248; methylprednisolone, n = 2), 498 were not given corticosteroids and in 259 patients data for corticosteroids were missing. Fatal outcome was observed in 8.9% of the patients in the corticosteroid-treated group vs. 17.9% in the non-corticosteroid-treated group (p <0.001), resulting in an odds ratio (OR) of 0.57 with a 95% confidence interval (CI) of 0.40-0.81 adjusted for age, sex, mental status, and door-to-antibiotic time. In patients with meningitis caused by S. pneumoniae, mortality was 10.2% in the corticosteroid-treated group and 21.3% in the non-corticosteroid-treated group (p <0.001) with an adjusted OR of 0.50 (95% CI 0.31-0.80). In ABM patients with non-pneumococcal aetiology the adjusted OR was 0.71 (95% CI 0.40-1.26). Lower mortality was observed in the corticosteroid-treated group with impaired mental status, whereas no significant difference was found in patients with unaffected mental status. The adjusted ORs for betamethasone and dexamethasone were 0.49 (95% CI 0.28-0.84) and 0.61 (95% CI 0.37-1.01), respectively. Corticosteroid treatment decreases mortality in ABM and should be administered initially with antibiotics in adult ABM patients with impaired mental status regardless of presumed aetiology. Betamethasone seems to be at least as effective as dexamethasone.

Community-onset Staphylococcus aureus Surveillance Programme annual report, 2012.

In 2012, the Australian Group on Antimicrobial Resistance (AGAR) conducted a community-onset period-prevalence survey of clinical Staphylococcus aureus isolated from hospital outpatients and general practice patients including nursing homes, long term care facilities and hospice patients. Day surgery and dialysis patients were excluded. Twenty-nine medical microbiology laboratories from all state and mainland territories participated. Isolates were tested by Vitek2® (AST-P612 card). Results were compared with previous AGAR community surveys. Nationally, the proportion of S. aureus that were methicillin-resistant S. aureus (MRSA) increased significantly from 11.5% in 2000 to 17.9% in 2012 (P<0.0001). Resistance to the non-ß-lactam antimicrobials varied between regions. No resistance was detected to vancomycin, teicoplanin or linezolid. Resistance in methicillin susceptible S. aureus was rare apart from erythromycin (12.8%) and was absent for vancomycin, teicoplanin, linezolid and daptomycin. The proportion of S. aureus characterised as health care-associated MRSA (HA-MRSA) was 5.1%. Three HA-MRSA clones were characterised, with 72.9% and 26.4% of HA-MRSA classified as ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA) respectively. Multi-clonal community-associated MRSA (CA-MRSA) accounted for 12.5% of all S. aureus. Regional variation in resistance in MRSA was primarily due to the differential distribution of the 2 major HA-MRSA clones; ST239-III [3A] (Aus-2/3 EMRSA), which is resistant to multiple non-ß-lactam antimicrobials, and ST22-IV [2B] (EMRSA-15), which is resistant to ciprofloxacin and typically erythromycin. Although the majority of CA-MRSA were non-multi-resistant, a significant expansion of Panton-Valentine leukocidin (PVL) positive CA-MRSA clones has occurred nationally. The mean age of patients (31.7 years, 95% CI 28.9-34.5) with a PVL positive CA-MRSA infection was significantly lower (P<0.0001), than the mean age of patients with a PVL negative CA-MRSA infection (55.7 years, 95% CI 50.7-60.6). This shift in the molecular epidemiology of MRSA clones in the Australian community will potentially increase the number of young Australians with skin and soft tissue infections requiring hospitalisation.

Community-onset Gram-negative Surveillance Program annual report, 2012.

The Australian Group on Antimicrobial Resistance performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric Gram-negative pathogens. The 2012 survey focussed on community-onset infections, examining isolates from urinary tract infections from patients presenting to outpatient clinics, emergency departments or to community practitioners. In 2012, 2,025 Escherichia coli, 538 Klebsiella species and 239 Enterobacter species were tested using a commercial automated method (Vitek 2, BioMérieux) and results were analysed using Clinical and Laboratory Standards Institute breakpoints from January 2012. Of the key resistances, non-susceptibility to the third-generation cephalosporin, ceftriaxone, was found in 4.2% of E. coli and 4.6%-6.9% of Klebsiella spp. Non-susceptibility rates to ciprofloxacin were 6.9% for E. coli, 0.0%-3.5% for Klebsiella spp. and 0.8%-1.9% in Enterobacter spp, and resistance rates to piperacillin-tazobactam were 1.7%, 0.7%-9.2%, and 8.8%-11.4% for the same 3 groups respectively. Only 1 Enterobacter cloacae was shown to harbour a carbapenemase (IMP-4).

Community-acquired pneumonia: 2012 history, mythology, and science.

Pneumonia remains one of the major disease entities practicing physicians must manage. It is a leading cause of infection-related morbidity and mortality in all age groups, and a leading cause of death in those older than 65 years of age. Despite its frequency and importance, clinical questions have remained in the therapy of community-acquired pneumonia including when to start antibiotics, when to stop them, who to treat, and what agents to use. Answers to these questions have involved historical practice, mythology, and science-sometimes good science, and sometimes better science. How clinical decisions are made for patients with community-acquired pneumonia serves as an illustrative model for other problem areas of medicine and allows for insight as to how clinical decisions have been made and clinical practice established.

[Clostridium difficile epidemic, Chile 2012: report of the Chilean Society for Infectious Diseases. A scientific historical analysis]. / Epidemia de Clostridium difficile, Chile 2012: Informe de la Sociedad Chilena de Infectología. Una aproximación científico histórica.

A Summary Report from the Chilean Society for Infectious Diseases regarding the presence of a Clostridium difficile epidemic with several fatalities in Chile's premier emergency public hospital in Santiago is used to make a scientific historical analysis of the situation. This Summary Report identifies several hygienic and sanitary shortcomings that may have played a role in triggering this major epidemic. These include deficiencies in hand washing policies, overcrowding of beds in wards, relaxation of infection control policies, antimicrobial therapy mismanagement and lack of laboratory support. The relevance of these shortcomings to the epidemic is further supported by the lack of any laboratory evidence for the presence of hypertoxigenic strains of C. difficile. In an era of whole genome sequencing of pathogens to guide therapy, prevention, and epidemiological studies of infectious diseases, it is illuminating and sobering, as this report so clearly demonstrates, to realize that many epidemics of hospital infections still result from breakdowns in classical and ancillary asepsis and infection control measures developed in the nineteenth century by Semmelweis, Nightingale and Lister. As the Summary Report suggests, such hygienic breakdowns in countries like Chile are usually brought about by lack of implementation and regulation of national hospital infection control policies resulting from the shift of economic resources from the public to the private sector, despite the former being responsible for health care of 80% of the population.

Epidemia de Clostridium difficile, Chile 2012: Informe de la Sociedad Chilena de Infectología. Una aproximación científico histórica / Clostridium difficile epidemic, Chile 2012: Report of the Chilean Society for Infectious Diseases. A scientific historical analysis

A Summary Report from the Chilean Society for Infectious Diseases regarding the presence of a Clostridium difficile epidemic with several fatalities in Chile's premier emergency public hospital in Santiago is used to make a scientific historical analysis of the situation. This Summary Report identifies several hygienic and sanitary shortcomings that may have played a role in triggering this major epidemic. These include deficiencies in hand washing policies, overcrowding of beds in wards, relaxation of infection control policies, antimicrobial therapy mismanagement and lack of laboratory support. The relevance of these shortcomings to the epidemic is further supported by the lack of any laboratory evidence for the presence of hypertoxigenic strains of C. difficile. In an era of whole genome sequencing of pathogens to guide therapy, prevention, and epidemiological studies of infectious diseases, it is illuminating and sobering, as this report so clearly demonstrates, to realize that many epidemics of hospital infections still result from breakdowns in classical and ancillary asepsis and infection control measures developed in the nineteenth century by Semmelweis, Nightingale and Lister. As the Summary Report suggests, such hygienic breakdowns in countries like Chile are usually brought about by lack of implementation and regulation of national hospital infection control policies resulting from the shift of economic resources from the public to the private sector, despite the former being responsible for health care of 80% of the population.

Methicillin-resistant Staphylococcus aureus in Canada: a historical perspective and lessons learned.

The history of methicillin-resistant Staphylococcus aureus (MRSA) in Canada has many similarities to MRSA evolution worldwide, but especially to that in the United States and United Kingdom. Reports of MRSA occurred as early as 1964, and community isolates were cited in the 1970s. Nosocomial outbreaks were becoming common by 1978 and flourished gradually thereafter. Endemic institutional MRSA became predominant in the 1990s, threatening large teaching hospitals in particular. In the last decade, both hospital-acquired and community-acquired MRSA have created major medical problems in Canada. More recently, an epidemic of Canadian community-acquired MRSA-10, has led to heightened public health concerns. Canadian contributions to MRSA science are numerous, with organized surveillance continuing to mature across the nation. A typing system for epidemic clones is now available and is being judiciously applied. Estimated costs for MRSA surveillance, treatment, and control are extraordinary, paralleling the dramatic rise in the number of MRSA isolations. Whereas surveillance continues to form an essential aspect of MRSA management, control, eradication, and overall diminution, MRSA reservoirs deserve much greater attention. Such efforts, however, must be as widely publicized in the community and in patient homes as they are in medical institutions responsible for both acute and long-term care.

Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era.

Staphylococcus aureus is the leading cause of bacterial infections in developed countries and produces a wide spectrum of diseases, ranging from minor skin infections to fatal necrotizing pneumonia. Although S. aureus infections were historically treatable with common antibiotics, emergence of drug-resistant organisms is now a major concern. Methicillin-resistant S. aureus (MRSA) was endemic in hospitals by the late 1960s, but it appeared rapidly and unexpectedly in communities in the 1990s and is now prevalent worldwide. This Review focuses on progress made toward understanding the success of community-associated MRSA as a human pathogen, with an emphasis on genome-wide approaches and virulence determinants.

School closure may be effective in reducing transmission of respiratory viruses in the community.

Proposed measures to contain pandemic influenza include school closure, although the effectiveness of this has not been investigated. We examined the effect of a nationwide elementary school strike in Israel in 2000 on the incidence of influenza-like illness. In this historical observational study of 1.7 million members of a preferred provider organization, we analysed diagnoses from primary-care visits during the winter months in 1998-2002. We calculated the weekly ratio of influenza-like diagnoses to non-respiratory diagnoses, and fitted regression models for school-aged children, children's household members, and all other individuals aged >12 years. For each population the steepest drop in the ratio of influenza-like diagnoses to non-respiratory diagnoses occurred in the strike year 2 weeks after the start of the strike. The changes in the weekly ratio of influenza-like diagnoses to non-respiratory diagnoses were statistically significant (P=0.0074) for school children for the strike year compared to other years. A smaller decrease was also seen for the adults with no school-aged children in 1999 (P=0.037). The Chanukah holiday had a negative impact on the ratio for school-aged children in 1998, 1999 and 2001 (P=0.008, 0.006 and 0.045, respectively) and was statistically significant for both adult groups in 1999 and for adults with no school-aged children in 2001. School closure should be considered part of the containment strategy in an influenza pandemic.

Plagues in the ICU: a brief history of community-acquired epidemic and endemic transmissible infections leading to intensive care admission.

The ability to diagnose and treat infectious diseases and handle infectious disease outbreaks continues to improve. For the most part, the major plagues of antiquity remain historical footnotes, yet, despite many advances, there is clear evidence that major pandemic illness is always just one outbreak away. In addition to the HIV pandemic, the smaller epidemic outbreaks of Legionnaire's disease, hantavirus pulmonary syndrome, and severe acute respiratory syndrome, among many others, points out the potential risk associated with a lack of preplanning and preparedness. Although pandemic influenza is at the top of the list when discussing possible future major infectious disease outbreaks, the truth is that the identity of the next major pandemic pathogen cannot be predicted with any accuracy. We can only hope that general preparedness and the lessons learned from previous outbreaks suffice.

Historical and regulatory perspectives on the treatment effect of antibacterial drugs for community-acquired pneumonia.

A noninferiority margin based on the treatment effect of antibacterial drugs is required for noninferiority studies of community-acquired pneumonia. A quantitative estimate of treatment effect is generally determined from placebo-controlled trials, but, since the mid-to-late 1930s, no studies have compared outcomes for patients who received placebo (or no specific therapy) with those for patients who received an antibacterial drug for treatment of community-acquired pneumonia. In this article, early controlled studies, as well as observational data, are reviewed, and the beneficial effect of antibacterial drugs on mortality rates among patients with pneumococcal pneumonia is demonstrated. However, because these data were obtained in the early 20th century, several important factors have changed, including patient populations, the etiological agents of pneumonia, and medical standards of care. Thus, the applicability of these studies to the determination of a noninferiority margin for contemporary trials for community-acquired pneumonia remains in question.

Antimicrobial resistance: prognosis for public health.

Antimicrobial resistance poses a significant threat to public health worldwide, with certain infections already being untreatable with antibiotics. Increasing resistance is resulting from antimicrobial use coupled with various epidemiological factors that enhance transmission of drug-resistant organisms, and the problem is likely to worsen. Control of antimicrobial resistance is feasible, but will be difficult.

Clinical overview of typical Mycoplasma pneumoniae infections.

A number of clinical and epidemiological factors permit the tentative identification of Mycoplasma pneumoniae infections. These selective factors can be considered the mainstay of diagnosis because they facilitate intelligent and efficient use of laboratory tests. The laboratory, in turn, through identification of the causative agent, augments both clinical and epidemiological data. The laboratory can better serve its purpose as more rapid, sensitive, and specific diagnostic methods come into use.

Aetiology and treatment of community-acquired pneumonia in adults: an historical perspective.

Community-acquired pneumonia is common. Most disease is mild but mortality among hospitalized patients is 5-20%. The most common aetiological pathogens are Streptococcus pneumoniae, Haemophilus influenzae, and the 'atypical' organisms, Mycoplasma pneumoniae, Legionella pneumophila and Chlamydia pneumoniae. Less common pathogens account for 10-30% of cases and the aetiology cannot be determined in one-third to one-half of cases. Classification by aetiology and initiation of specific antimicrobial therapy are difficult and treatment is often initiated empirically. Ampicillin (or amoxycillin) or erythromycin are inexpensive and effective for most patients, but their use in combination, the addition of a beta-lactamase inhibitor (e.g. amoxycillin/clavulanate) or the substitution of an expanded spectrum cephalosporin (e.g. cefuroxime) should be considered for patients with more serious illnesses or pathogens likely to be drug-resistant. Fluoroquinolones such as ciprofloxacin or ofloxacin would be acceptable if adequacy for treating pneumococcal infections were likely. New macrolides, such as azithromycin and clarithromycin, and new fluoroquinolones, such as temafloxacin and sparfloxacin, have theoretical advantages over previously available drugs, but superior efficacy has not yet been demonstrated satisfactorily. Pneumococcal resistance in various parts of the world is modifying traditional treatment. Currently, there is no drug of choice for the empirical treatment of community-acquired pneumonia.