The advent of sensitive enhanced culture (metaculturomic) and culture-independent DNA-based (metagenomic) methods has revealed a rich collection of microbial species that inhabit the human urinary tract. Known as the urinary microbiome, this community of microbes consists of hundreds of distinct species that range across the entire phylogenetic spectrum. This new knowledge clashes with standard clinical microbiology laboratory methods, established more than 60 years ago, that focus attention on a relatively small subset of universally acknowledged uropathogens. Increasing reports support the hypothesis that this focus is too narrow. Single uropathogen reports are common in women with recurrent urinary tract infection (UTI), although wider disruption of their urinary microbiome is likely. Typical “UTI” symptoms occur in patients with “no growth” reported from standard culture and sometimes antibiotics improve these symptoms. Metaculturomic and metagenomic methods have repeatedly detected fastidious, slow growing, and/or anaerobic microbes that are not detected by the standard test in urine samples of patients with lower urinary tract symptoms. Many of these microbes are also detected in serious non-urinary tract infections, providing evidence that they can be opportunistic pathogens. In this review, we present a set of poorly understood, emerging, and suspected uropathogens. The goal is to stimulate research into the biology of these microbes with a focus on their life as commensals and their transition into pathogens 

Beyond the usual suspects: emerging uropathogens in the microbiome age

We read with interest the article by Luraschi and colleagues on caspofungin and Pneumocystis jirovecii published in Antimicrobial Agents and Chemotherapy (1). Caspofungin is an echinocandin which is widely used as the first-line treatment of systemic candidiasis (2). This drug is a noncompetitive inhibitor of the subunit GSC1 of the enzymatic complex involved in 1,3-D-glucan synthesis, 1,3-glucan being a major cell wall component of most fungi. The main goal of the aforementioned study was to assess in vitro sensitivity of P. jirovecii, the human-specific Pneumocystis species, to caspofungin. Nonsynonymous mutations that confer resistance to caspofungin have been identified on the gsc1 gene of the fungal pathogen C. albicans. The study performed by Luraschi and colleagues concerns site-directed mutagenesis based on mutations previously identified within the C. albicans gsc1 gene and the construction of Saccharomyces cerevisiae deletants for the gsc1 gene followed by their complementation with the gsc1 gene of wild or mutant P. jirovecii, Pneumocystis murina (the specific species in mice), and Pneumocystis carinii (the specific species in rats) organisms. The results showed that the drug was effective in vitro against P. jirovecii, P. murina, and P. carinii as well. In vivo efficiency of caspofungin for treating Pneumocystis sp. infections has been established using rat and mouse models (3). Nonetheless, the drug essentially depletes Pneumocystis asci in the infected lungs, whereas it is less efficient against trophic forms (3). These results may be due to the absence or rarity of 1,3-D-glucan in trophic forms and the abundance of this component in ascus walls. In this context, a potential synergistic combination based on low doses of caspofungin and co-trimoxazole and targeting asci and trophic forms has been evaluated using a mouse model. It was shown that P. murina could be eradicated within the lungs by this combined regimen (4). Similar combined regimens in patients with Pneumocystis pneumonia (PCP) have been reported (5–16) (Table 1). In a recent study, the gene expression profiles of P. murina were compared between infected untreated mice and those treated with an echinocandin; results suggested that ascus formation may be necessary for Pneumocystis proliferation (17). These findings may explain in part the efficiency of caspofungin monotherapy in patients developing P. jirovecii infections, as described in four case reports (eight patients) (18–21; Table 1). Conversely, three case reports described the apparent failure of caspofungin treatment in nine patients with PCP (21, 22, 23, Table 1). Thus, efficiency of echinocandins and specifically that of caspofungin to treat P. jirovecii infections in humans remains a subject of controversy. Be that as it may, original results of Luraschi and colleagues that were obtained through a fundamental approach bring strong arguments for the use of caspofungin for PCP treatment in humans. These results render it necessary to implement clinical Citation Nevez G, Le Gal S. 2019. Caspofungin and Pneumocystis pneumonia: it is time to go ahead. Antimicrob Agents Chemother 63:e01296-19. https://doi.org/10.1128/AAC .01296-19. Copyright © 2019 American Society for Microbiology. All Rights Reserved. Address correspondence to Gilles Nevez, gilles.nevez@univ-brest.fr. For the author reply, see https://doi.org/10 .1128/AAC.01320-19. Published LETTER TO THE EDITOR

Caspofungin and Pneumocystis Pneumonia: It Is Time To Go Ahead.

Scientific rationale for inhaled caspofungin to treat Pneumocystis pneumonia: A therapeutic innovation likely relevant to investigate in a near future….

This study was conducted at one of the largest poultry companies in Kuwait during November and December 2019 to evaluate the microbiological threats of Escherichia coli (APEC), Salmonella spp., and Aspergillus fumigatus to chickens in fattening houses by counting and identifying the microorganisms by culturing and pyrosequencing analysis. During the fattening cycle, the temperature and humidity ranged between 23.6°C and 29°C and 64.1% and 87.1%, respectively. The total bacterial population and Aspergillus fumigatus measured in the indoor and outdoor air exhibited a linear relationship during the fattening cycle. The total bacterial and Aspergillus concentrations determined during the cycle ranged between 150 and 2000 CFU/m3 and 0 and 1000 CFU/m3, respectively. E. coli and Salmonella spp. concentrations determined during the cycle ranged between 1 and 220 CFU/m3 and 4 and 110 CFU/m3, respectively. Pyrosequencing analysis of the air inside the houses at the end of the cycle revealed extensive biodiversity in the microorganisms, detecting 32 bacterial genera and 14 species. The identified species belonging to the genera Corynebacterium, Haemophilus, Streptococcus, Veillonella, and Aspergillus were identified as potentially affecting human and broiler health. The emission of potentially pathogenic bacteria to the outdoor environment from chicken housing can pose a considerable risk to human health and environmental microbial pollution. This study could guide the development of integrated control devices for monitoring microbes in broiler production facilities during chicken collection for transport to slaughterhouses.

/pdf/microbiological-indoor-and-outdoor-air-quality-in-chicken-3t2ozd3p.pdf

Microbiological Indoor and Outdoor Air Quality in Chicken Fattening Houses

www.transplantationdirect.com 1 CMV Infection Following mRNA SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients Shourjo Chakravorty, MD,1 Adam B. Cochrane, PharmD, MPH,2 Mitchell A. Psotka, MD, PhD,3 Anil Regmi, MD,4 Lauren Marinak, NP,5 Amy Thatcher, NP,3 Oksana A. Shlobin, MD,5 A. Whitney Brown, MD,5 Christopher S. King, MD, FCCP,5 Kareem Ahmad, MD,5 Vikramjit Khangoora, MD,5 Anju Singhal, MD,5 Steven D. Nathan, MD, FCCP,5 and Shambhu Aryal, MD, FCCP5

CMV Infection Following mRNA SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients

https://academicworks.medicine.hofstra.edu/cgi/viewcontent.cgi?article=6145&context=articles

Combination therapy with trimethoprim-sulfamethoxazole and caspofungin in a case of severe pneumocystis pneumonia

Streptococcus anginosus group (SAG) is a subgroup of viridans streptococci and can be found ubiquitously in normal human flora SAG is known to form invasive pyogenic infection when it becomes pathogenic Yet, SAG is a very rare cause of endocarditis, and there is a dearth of case reports on this topic We present a rare case of native bicuspid aortic valve endocarditis secondary to S anginosus that caused aortic insufficiency and ascending aortic aneurysm To our knowledge, this is the first well-documented case report of community-acquired S anginosus endocarditis on a bicuspid aortic valve in an immunocompetent patient The patient first presented with cough that was likely due to bronchus irritation from a 55 x 52 cm ascending aortic aneurysm He underwent aortic valve replacement with bovine bioprosthesis and ascending aortic aneurysm repairment and was treated with a two-week regimen of IV ceftriaxone and gentamicin followed by another four weeks of IV ceftriaxone He was eventually discharged to a rehabilitation facility SAG is usually susceptible to beta-lactam antibiotics The prognosis of SAG infection is usually good, but progression to bacteremia carries a poor outcome

/pdf/an-unusual-case-of-streptococcus-anginosus-endocarditis-in-a-4igalsqt2d.pdf

An Unusual Case of Streptococcus anginosus Endocarditis in a Healthy Host With Bicuspid Aortic Valve.

Vaccination with the inactivated influenza vaccine is routinely recommended for all patients before and after transplant, with reduction in complications noted in transplant recipients. The vaccine is relatively well tolerated with few mild side effects. Cytomegalovirus (CMV) infection can reactivate in both solid organ transplant and hematopoietic stem cell transplant recipients, with some patients progressing to disease. There are multiple factors known to contribute to reactivation and subsequent CMV disease, however vaccination has not been reported as a specific risk factor. We report on two renal transplant recipients who were seen to develop CMV viremia and CMV disease after receiving the Influenza vaccine. We review the literature regarding viremia occurring after vaccination in HIV patients (a similar group of immunocompromised patients).

Cytomegalovirus Viremia in Renal Transplant Recipients After Influenza Vaccination.

Epididymitis associated with bacteremic pneumococcal pneumonia.

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Combination therapy with trimethoprim-sulfamethoxazole and caspofungin in a case of severe pneumocystis pneumonia

An Unusual Case of Streptococcus anginosus Endocarditis in a Healthy Host With Bicuspid Aortic Valve.

Cytomegalovirus Viremia in Renal Transplant Recipients After Influenza Vaccination.

Epididymitis associated with bacteremic pneumococcal pneumonia.