Coinfections and Superinfections Associated with COVID-19 in Colombia: A Narrative Review.

The COVID-19 pandemic has had significant impacts on healthcare systems around the world, including in Latin America. In Colombia, there have been over 23,000 confirmed cases and 100 deaths since 2022, with the highest number of cases occurring in females and the highest number of deaths in males. The elderly and those with comorbidities, such as arterial hypertension, diabetes mellitus, and respiratory diseases, have been particularly affected. Coinfections with other microorganisms, including dengue virus, Klebsiella pneumoniae, and Mycobacterium tuberculosis, have also been a significant factor in increasing morbidity and mortality rates in COVID-19 patients. It is important for surveillance systems to be improved and protocols to be established for the early detection and management of coinfections in COVID-19. In addition to traditional treatments, alternatives such as zinc supplementation and nanomedicine may have potential in the fight against COVID-19. It is also crucial to consider the social, labor, educational, psychological, and emotional costs of the pandemic and to address issues such as poverty and limited access to potable water in order to better prepare for future pandemics.

Lianhuaqingwen capsule inhibits non-lethal doses of influenza virus-induced secondary Staphylococcus aureus infection in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Lianhuaqingwen capsule (LH-C) is a traditional Chinese medicine (TCM), consisting of two prescriptions, Ma-xing-shi-gan-tang (MXSGT) and Yinqiao San. It has been proven to have antiviral, antibacterial, and immunomodulatory effects in recent years. Clinically, it is commonly used in the treatment of respiratory tract infections. AIM OF THE STUDY: It was demonstrated in our previous studies that LH-C has an effect of antivirus and inhibits influenza virus-induced bacterial adhesion to respiratory epithelial cells through down-regulation of cell adhesion molecules in vitro. However, LH-C's effect against influenza-induced secondary bacterial infection in animal studies remains unclear. Therefore, in the present study, we established a mouse model of infection with non-lethal doses of influenza virus(H1N1) and secondary infection of Staphylococcus aureus (S. aureus), to investigate the potential effects of LH-C. METHODS: Experiments were carried out on BALB/c mice infecting non-lethal doses of H1N1 and non-lethal doses of S. aureus, and the viral, and bacterial doses were determined by observing and recording changes in the body weight, mortality, and pathological changes. Moreover, after LH-C treatment, the survival rate, body weight, lung index, viral titers, bacterial colonies, pathological changes, and the inflammatory cytokines in the mouse model have all been systematically determined. RESULTS: In the superinfection models of H1N1 and S. aureus, the mortality rate was 100% in groups of mice infected with 20 PFU/50 µL of H1N1 and 105 CFU/mL of S. aureus, 20 PFU/50 µL of H1N1 and 106 CFU/mL of S. aureus, 4 PFU/50 µL of H1N1 and 106 CFU/mL of S. aureus. The mortality rate was 50% in the group of mice infected with 4 PFU/50 µL of H1N1 and 105 CFU/mL of S. aureus. The mortality rate was 37.5% in the group of mice infected with 20 PFU/50 µL of H1N1 alone and in the group of mice infected with 2 PFU/50 µL of H1N1 and 106 CFU/mL of S. aureus. The mortality rate in the group of mice infected with 2 PFU/50 µL of H1N1 and 106 CFU/mL of S. aureus was 30%. The infected mice of 2 PFU/50 µL of H1N1 and 106 CFU/mL of S. aureus had a weight loss of nearly 10%. About the histopathological changes in the lung tissue of infection mice, severe lung lesions were found in the superinfection models. LH-C improved survival in the superinfected mice, significantly reduced lung index, lowered viral titers and bacterial loads, and alleviated lung damage. It reduced lung inflammation by down-regulating mRNA expression levels of inflammatory mediators like IL-6, IL-1ß, IL-10, TNF-α, IFN-ß, MCP-1, and RANTES. CONCLUSIONS: We found that superinfection from non-lethal doses of S. aureus following non-lethal doses of H1N1 was equally fatal in mice, confirming the severity of secondary infections. The ability of LH-C to alleviate lung injury resulting from secondary S. aureus infection induced by H1N1 was confirmed. These findings provided a further assessment of LH-C, suggesting that LH-C may have good therapeutic efficacy in influenza secondary bacterial infection disease.

Superinfection of hepatitis A virus in hepatocytes infected with hepatitis B virus.

Hepatitis A virus (HAV) infection is a major cause of acute hepatitis including acute liver failure. Hepatitis B infection (HBV) occurs worldwide, with the highest rates in Asian and African countries, and there are several reports that HAV infection may have a more severe clinical course in patients with chronic HBV infection. We previously demonstrated that Japanese miso extracts have inhibitory effects on HAV replication. In the present study, we examined the replication of HAV and HBV in a hepatocyte superinfection model and the inhibitory effects of Japanese miso extracts on both viruses. According to the results, HAV infection inhibited HBV replication in superinfected hepatocytes, and Japanese rice-koji miso extracts had inhibitory effects on HAV replication. Our findings provide useful information for clinicians in managing HAV infection in patients with chronic HBV infection.

Survival during influenza-associated bacterial superinfection improves following viral- and bacterial-specific monoclonal antibody treatment.

Postinfluenza bacterial superinfections cause increased morbidity and mortality compared with singular infection with influenza during both pandemics and seasonal epidemics. Vaccines and current treatments provide limited benefit, a rationale to conduct studies utilizing alternative therapies. FY1 and an optimized version, MEDI8852, anti-influenza HA mAbs, have been shown to neutralize influenza virus during singular influenza infection. MEDI4893*, an anti-Staphylococcus aureus α-toxin mAb, has been shown to improve survival when administered prophylactically prior to S. aureus pneumonia. Our objective was to determine if mAbs can improve survival during postinfluenza bacterial pneumonia. We administered FY1 in a murine model of postinfluenza methicillin-resistant S. aureus (MRSA) pneumonia and observed improved survival rates when given early during the course of influenza infection. Our findings indicate decreased lung injury and increased uptake and binding of bacteria by macrophages in the mice that received FY1 earlier in the course of influenza infection, corresponding to decreased bacterial burden. We also observed improved survival when mice were treated with a combination of FY1 and MEDI4893* late during the course of postinfluenza MRSA pneumonia. In conclusion, both FY1 and MEDI4893* prolong survival when used in a murine model of postinfluenza MRSA pneumonia, suggesting pathogen-specific mAbs as a possible therapeutic in the context of bacterial superinfection.

Prevention of influenza virus induced bacterial superinfection by standardized Echinacea purpurea, via regulation of surface receptor expression in human bronchial epithelial cells.

Viral infections may predispose the airways to secondary bacterial infections that can lead to unfavorable progression of principally self-limiting illnesses. Such complicated respiratory infections include pneumonia, bronchitis, sinusitis, acute otitis media, and sepsis, which cause high morbidity and lethality. Some of the pathogenic consequences of viral infections, like the expression of bacterial adhesion receptors and the disturbance of physical barrier integrity due to inflammation, may create permissive conditions for co-infections. Influenza virus A (H3N2) is a major pathogen that causes secondary bacterial infections and inflammation that lead to pneumonia. The herbal medicine Echinacea purpurea, on the other hand, has been widely used to prevent and treat viral respiratory infections, and recent clinical data suggest that it may prevent secondary infection complications as well. We investigated the role of standardized E. purpurea (Echinaforce® extract or EF) on H3N2-induced adhesion of live nontypeable Haemophilus influenzae (NTHi) and Staphylococcus aureus, along with the expression of bacterial receptors, intracellular adhesion molecule-1 (ICAM-1), fibronectin, and platelet activating factor receptor (PAFr), by BEAS-2B cells. Inflammatory processes were investigated by determining the cellular expression of IL-6 and IL-8 and the involvement of Toll-like receptor (TLR-4) and NFκB p65. We found that influenza virus A infection increased the adhesion of H. influenzae and S. aureus to bronchial epithelial cells via upregulated expression of the ICAM-1 receptor and, to some extent, of fibronectin and PAFr. Echinaforce (EF) significantly reduced the expression of ICAM-1, fibronectin, and PAFr and consequently the adhesion of both bacterial strains. EF also effectively prevented the super-expression of inflammatory cytokines by suppressing the expression of NFκB and possibly TLR-4. These results indicate that E. purpurea has the potential to reduce the risk of respiratory complications by preventing virus-induced bacterial adhesion and through the inhibition of inflammation super-stimulation (cytokine storms).

Prosthetic joint infection caused by Trueperella bernardiae.

Trueperella bernardiae is a Gram-positive coryneform bacilli which role as human pathogen is unknown because it has been usually considered a contaminant. Furthermore its identification by biochemical test was difficult. We describe a prosthetic joint infection in a women who years ago underwent a total knee replacement with superinfection and necrosis of the patellar tendon as major complications. In the sample of synovial fluid collected grew a gram-positive bacilli which was identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) as T. bernardiae. The patient was treated with ciprofloxacin and currently preserves the prosthesis without signs of infection.

Superinfection of sows with Cystoisospora suis ante partum leads to a milder course of cystoisosporosis in suckling piglets.

Cystoisospora (syn. Isospora) suis is a leading cause of diarrheal disease in neonatal piglets. To address the possibility of maternal immunization against C. suis infection six non-naïve pregnant sows were superinfected with 100,000 oocysts 2 weeks ante partum and compared to non-superinfected animals. Their piglets were infected with 1000 oocysts on the third day of life. Clinical and parasitological parameters as well as antibody titers in colostrum/milk and blood of sows and in the blood of piglets were evaluated by IFAT against sporozoites and merozoites from 2 weeks ante partum until the 35th day after birth. For IFAT two different invasive stages of C. suis were used to find possible differences between the immune response against the initially infectious stages (sporozoites) and later occurring asexual developmental stages (merozoites), which might be responsible for persisting/extraintestinal infections. IFN-γ production of PBMC and piglet splenocytes was determined by ELISPOT. Maternal superinfection resulted in increased titers of IgA, IgM and IgG in colostrum and milk as well as in the blood of sows and their piglets. Oocyst shedding and diarrhea were observed in the offspring of both groups, but piglets of superinfected sows showed significantly reduced oocyst shedding and less diarrhea. This protective effect was correlated with increased titers of antibodies, especially IgA, in colostrum, milk and blood serum of sows and piglets, and with the reactivity of splenocytes to parasite antigen. Superinfection of sows ante partum could partially protect piglets against the clinical outcome of experimental infection. Both colostrum and milk contain maternal protective substances as the effect of protection was highly correlated with antibody titers during the first 2 weeks of life. IgA in different substrates may serve as a marker for the level of protection against clinical cystoisosporosis.

Acute sinusitis in children.

Acute rhinosinusitis is a common illness in children. Viral upper respiratory tract infection is the most common presentation of rhinosinusitis. Most children resolve the infection spontaneously and only a small proportion develops a secondary bacterial infection. The proper choice of antibiotic therapy depends on the likely infecting pathogens, bacterial antibiotic resistance, and pharmacologic profiles of antibiotics. Amoxicillin-clavulanate is currently recommended as the empiric treatment in those requiring antimicrobial therapy. Isolation of the causative agents should be considered in those who failed the initial treatment. In addition to antibiotics, adjuvant therapies and surgery may be used in the management of acute bacterial rhinosinusitis.

The risks of targeting co-inhibitory pathways to modulate pathogen-directed T cell responses.

The identification of T cell co-inhibition as a central mechanism in the regulation of adaptive immunity during infectious diseases provides new opportunities for immunotherapeutic interventions. However, the fact that T cell activity is frequently downregulated during pathogen-directed responses suggests a pivotal physiological role of co-inhibitory pathways during infectious disease. Reports of exacerbated immunopathology in conditions of impaired co-inhibition foster the view that downregulation of T cell activity is an essential negative feedback mechanism that protects from excessive pathogen-directed immunity. Thus, targeting co-inhibitory pathways can bear detrimental potential through the deregulation of physiological processes. Here, we summarize recent preclinical and clinical interventions that report immune-related adverse events after targeting co-inhibitory pathways.

Severe pneumonitis after fire eating.

A 38-year-old, previously healthy fire eater presented with severe pneumonitis after incidental aspiration of an unquantifiable amount of petroleum. The chest CT revealed extensive pulmonary consolidations, and the laboratory results showed massively elevated inflammatory markers. An intravenous antibiotic treatment was started and, after improvement of symptoms and inflammatory markers, continued orally for a total of 3 weeks, despite negative results of blood cultures and urinary pneumococcal and legionella antigen tests. The patient's symptoms subsided completely, and a CT scan 10 weeks after the accident showed complete resolution of the lung consolidations. Aspiration of petroleum is associated with a severe inflammatory response of the lung, but if bacterial superinfection can be prevented with early antibiotic treatment, even a severe presentation of a fire eater's lung usually follows a benign course with complete recovery.

A fatal case of strongyloidiasis stercoralis superinfection in an immunocompromized patient.

Strongyloides stercoralis is a disease of worldwide distribution particularly in the immunocompromized patients, especially who are receiving systemic steroids or immunosuppressant therapy, early diagnosis is the key for life safety. A fatal case of chronic strongyloidiasis is reported in an immunocompromized patient with complicated pulmonary infection.

Ceftriaxone and ciprofloxacin restriction in an intensive care unit: less incidence of Acinetobacter spp. and improved susceptibility of Pseudomonas aeruginosa / Restricción del uso de ceftriaxona y ciprofloxacino en una unidad de cuidados intensivos: menor incidencia de Acinetobacter spp. y mayor sensibilidad de Pseudomonas aeruginosa

Objective. To determine whether restricting the use of ceftriaxone and ciprofloxacin could significantly reduce colonization and infection with resistant Gram-negative bacilli (r-GNB). Methods. A two-phase prospective study (before/after design) was conducted in an intensive care unit in two time periods (2004–2006). During phase 1, there was no antibiotic restriction. During phase 2, use of ceftriaxone or ciprofloxacin was restricted. Results. A total of 200 patients were prospectively evaluated. In phase 2, the use of ceftriaxone was reduced by 93.6% (P = 0.0001) and that of ciprofloxacin by 65.1% (P = 0.041), accompanied by a 113.8% increase in use of ampicillin-sulbactam (P = 0.002). During phase 1, 48 GNB were isolated [37 r-GNB (77.1%) and 11 non-r-GNB (22.9%)], compared with a total of 64 during phase 2 [27 r-GNB (42.2%) and 37 non-r-GNB (57.8%)] (P = 0.0002). Acinetobacter spp. was isolated 13 times during phase 1 and 3 times in phase 2 (P = 0.0018). The susceptibility of Pseudomonas aeruginosa to ciprofloxacin increased from 40.0% in phase 1 to 100.0% in phase 2 (P = 0.0108). Conclusions. Restriction of ceftriaxone and ciprofloxacin reduced colonization byAcinetobacter spp. and improved the susceptibility profile of P. aeruginosa.

Objetivo. Determinar si la restricción del uso de ceftriaxona y ciprofloxacino reduce significativamente la colonización y la infección por bacilos gramnegativos resistentes. Métodos. Se efectuó un estudio prospectivo de dos fases (diseño antes/después de la intervención) en una unidad de cuidados intensivos en dos períodos sucesivos entre los años 2004 y 2006. Durante la fase 1, no hubo ninguna restricción de antibióticos. Durante la fase 2, se restringió el uso de ceftriaxona y ciprofloxacino. Resultados. Se evaluó prospectivamente a 200 pacientes en total. En la fase 2, el uso de ceftriaxona se redujo en 93,6% (P = 0,0001) y el de ciprofloxacino en 65,1% (P = 0,041), lo que se acompañó de un aumento de 113,8% en el uso de ampicilina/sulbactam (P = 0,002). Durante la fase 1, se aislaron 48 bacilos gramnegativos (37 resistentes [77,1%] y 11 no resistentes [22,9%]), en comparación con un total de 64 durante la fase 2 (27 resistentes [42,2%] y 37 no resistentes [57,8%]) (P = 0,0002). Se aisló Acinetobacter spp. 13 veces durante la fase 1 y 3 veces en la fase 2 (P = 0,0018). La sensibilidad de Pseudomonas aeruginosa al ciprofloxacino aumentó de 40,0% en la fase 1 a 100,0% en la fase 2 (P = 0,0108). Conclusiones. La restricción del uso de ceftriaxona y ciprofloxacino redujo la colonización por Acinetobacter spp. y mejoró el perfil de sensibilidad de P. aeruginosa.

New antimicrobial therapies used against fungi present in subgingival sites--a brief review.

Although the main reservoir of Candida spp. is believed to be the buccal mucosa, these microorganisms can coaggregate with bacteria in subgingival biofilm and adhere to epithelial cells. The treatment of periodontal disease includes scaling and root planning (SRP) associated with proper oral hygiene. However, some patients may have negative responses to different therapeutic procedures, with a continuous loss of insertion, so the use of antimicrobials is needed as an adjuvant to SRP treatment. The use of a broad-spectrum antibiotic, such as tetracycline and metronidazole, as an aid in periodontal treatment has also been a factor for the development of superinfections by resistant bacteria and Candida species, even in patients with HIV. In the dental practice, the most commonly used antifungals are nystatin and fluconazole. However, the introduction of new drugs like the next generation of azoles is essential before the onset of emergent species in periodontal disease. Plants are good options for obtaining a wide variety of drugs. This alternative could benefit a large population that uses plants as a first treatment option. Plants have been used in medicine for a long time and are extensively used in folk medicine, because they represent an economic alternative, are easily accessible and are applicable to various diseases. Herein, we briefly review the literature pertaining the presence of Candida sp. in periodontal pockets, the conventional antifungal resistance and new therapies that include natural antifungal agents are reviewed.

Host-mediated regulation of superinfection in malaria.

In regions of high rates of malaria transmission, mosquitoes repeatedly transmit liver-tropic Plasmodium sporozoites to individuals who already have blood-stage parasitemia. This manifests itself in semi-immune children (who have been exposed since birth to Plasmodium infection and as such show low levels of peripheral parasitemia but can still be infected) older than 5 years of age by concurrent carriage of different parasite genotypes at low asymptomatic parasitemias. Superinfection presents an increased risk of hyperparasitemia and death in less immune individuals but counterintuitively is not frequently observed in the young. Here we show in a mouse model that ongoing blood-stage infections, above a minimum threshold, impair the growth of subsequently inoculated sporozoites such that they become growth arrested in liver hepatocytes and fail to develop into blood-stage parasites. Inhibition of the liver-stage infection is mediated by the host iron regulatory hormone hepcidin, whose synthesis we found to be stimulated by blood-stage parasites in a density-dependent manner. We mathematically modeled this phenomenon and show how density-dependent protection against liver-stage malaria can shape the epidemiological patterns of age-related risk and the complexity of malaria infections seen in young children. The interaction between these two Plasmodium stages and host iron metabolism has relevance for the global efforts to reduce malaria transmission and for evaluation of iron supplementation programs in malaria-endemic regions.

Ceftriaxone and ciprofloxacin restriction in an intensive care unit: less incidence of Acinetobacter spp. and improved susceptibility of Pseudomonas aeruginosa.

OBJECTIVE: To determine whether restricting the use of ceftriaxone and ciprofloxacin could significantly reduce colonization and infection with resistant Gram-negative bacilli (r-GNB). METHODS: A two-phase prospective study (before/after design) was conducted in an intensive care unit in two time periods (2004-2006). During phase 1, there was no antibiotic restriction. During phase 2, use of ceftriaxone or ciprofloxacin was restricted. RESULTS: Atotal of 200 patients were prospectively evaluated. In phase 2, the use of ceftriaxone was reduced by 93.6% (P = 0.0001) and that of ciprofloxacin by 65.1% (P = 0.041), accompanied by a 113.8% increase in use of ampicillin-sulbactam (P = 0.002).During phase 1, 48 GNB were isolated [37 r-GNB (77.1%) and 11 non-r-GNB (22.9%)], compared with a total of 64 during phase 2 [27 r-GNB (42.2%) and 37 non-r-GNB (57.8%)](P = 0.0002). Acinetobacter spp. was isolated 13 times during phase 1 and 3 times in phase 2 (P = 0.0018). The susceptibility of Pseudomonas aeruginosa to ciprofloxacin increased from 40.0% in phase 1 to 100.0% in phase 2 (P = 0.0108). CONCLUSIONS: Restriction of ceftriaxone and ciprofloxacin reduced colonization by Acinetobacter spp. and improved the susceptibility profile of P. aeruginosa.