Pulmonary Coinfection Research Articles

Recurrent pulmonary nocardiosis due to Nocardia Otitidiscaviarum in a patient with isolated CD4 lymphocytopenia: a case report

BackgroundIdiopathic CD4 lymphocytopenia (ICL) is an underdiagnosed immunodeficiency syndrome characterised by persistent low CD4 counts in the absence of HIV and other causes of lymphocytopenia. ICL patients are susceptible to opportunistic infections, with human papillomavirus, cryptococcal, and tuberculosis being the most common infections reported. Nocardiosis is rarely reported in patient with ICL.Case PresentationWe herein discuss a 46-year-old female presented with complaints of weight loss, low grade fever and cough with expectoration from last four months. The patient was diagnosed with pulmonary nocardiosis and aspergillosis co-infection four years back; in addition she also had ICL. Subsequently, the patient was lost in follow-up and readmitted four years later. Bronchoalveolar lavage sample shows the presence of acid-fast bacilli in modified gram stain, which later identified as Nocardia otitidiscaviarum by metagenomic next-generation sequencing. Her CD4 counts were still found low (298 cells/mm3). After an initial improvement with trimethoprim-sulfamethoxazole (TMP-SMX), she was commenced on indefinite secondary prophylaxis.ConclusionsNocardiosis without usual risk factors should be evaluated for ICL. This case emphasize the importance of periodic follow-up with CD4 count monitoring and secondary prophylaxis therapy to prevent recurrence or the emergence of new infections in ICL.Clinical trial numberNot applicable.

Successful treatment of mixed pulmonary Aspergillus and Mucor infection using intrabronchial amphotericin B infusion: a case report and literature review

BackgroundReports of pulmonary aspergillosis and mucormycosis co-infections are rare; thus, limited guidance is available on early diagnosis and treatment. We present a case of mixed pulmonary Aspergillus and Mucor infection and review the literature regarding this co-infection. The diagnosis and treatment methods are summarized to improve clinicians’ understanding of the disease and to facilitate early diagnosis and treatment.Case presentationA 60-year-old male farmer with poorly controlled diabetes mellitus was admitted to hospital with a fever of unknown origin that had been present for 15 days and pulmonary aspergillosis complicated by Mucor spp. infection. Because multiple lobes were involved, the infection worsened despite surgical resection and antifungal therapy. Finally, we treated this patient with a bronchoscopic infusion of amphotericin B. After four courses of bronchoscopic amphotericin B infusion, we observed rapid clinical improvement and subsequent resolution of pulmonary infiltrates.ConclusionOur case highlights the use of bronchoscopy in the successful clinical treatment of invasive fungal diseases of the lung.

Pulmonary non-tuberculous mycobacteria and Mycobacterium tuberculosis complex co-infection: A pragmatic approach to its diagnosis and management in South Africa.

Pulmonary non-tuberculous mycobacteria and Mycobacterium tuberculosis complex co-infection: A pragmatic approach to its diagnosis and management in South Africa.

Concurrent TB and HIV therapies effectively control clinical reactivation of TB during co-infection but fail to eliminate chronic immune activation.

The majority of Human Immunodeficiency Virus (HIV) negative individuals exposed to Mycobacterium tuberculosis (Mtb) control the bacillary infection as latent TB infection (LTBI). Co-infection with HIV, however, drastically increases the risk to progression to tuberculosis (TB) disease. TB is therefore the leading cause of death in people living with HIV (PLWH) globally. Combinatorial antiretroviral therapy (cART) is the cornerstone of HIV care in humans and reduces the risk of reactivation of LTBI. However, the immune control of Mtb infection is not fully restored by cART as indicated by higher incidence of TB in PLWH despite cART. In the macaque model of co-infection, skewed pulmonary CD4+ TEM responses persist, and new TB lesions form despite cART treatment. We hypothesized that regimens that concurrently administer anti-TB therapy and cART would significantly reduce TB in co-infected macaques than cART alone, resulting in superior bacterial control, mitigation of persistent inflammation and lasting protective immunity. We studied components of TB immunity that remain impaired after cART in the lung compartment, versus those that are restored by concurrent 3 months of once weekly isoniazid and rifapentine (3HP) and cART in the rhesus macaque (RM) model of LTBI and Simian Immunodeficiency Virus (SIV) co-infection. Concurrent administration of cART + 3HP did improve clinical and microbiological attributes of Mtb/SIV co-infection compared to cART-naïve or -untreated RMs. While RMs in the cART + 3HP group exhibited significantly lower granuloma volumes after treatment, they, however, continued to harbor caseous granulomas with increased FDG uptake. cART only partially restores the constitution of CD4 + T cells to the lung compartment in co-infected macaques. Concurrent therapy did not further enhance the frequency of reconstituted CD4+ T cells in BAL and lung of Mtb/SIV co-infected RMs compared to cART, and treated animals continued to display incomplete reconstitution to the lung. Furthermore, the reconstituted CD4+ T cells in BAL and lung of cART + 3HP treated RMs exhibited an increased frequencies of activated, exhausted and inflamed phenotype compared to LTBI RMs. cART + 3HP failed to restore the effector memory CD4+ T cell population that was significantly reduced in pulmonary compartment post SIV co-infection. Concurrent therapy was associated with the induction of Type I IFN transcriptional signatures and led to increased Mtb-specific TH1/TH17 responses correlated with protection, but decreased Mtb-specific TNFa responses, which could have a detrimental impact on long term protection. Our results suggest the mechanisms by which Mtb/HIV co-infected individuals remain at risk for progression due to subsequent infections or reactivation due of persisting defects in pulmonary T cell responses. By identifying lung-specific immune components in this model, it is possible to pinpoint the pathways that can be targeted for host-directed adjunctive therapies for TB/HIV co-infection.

Prevalence and associated factors of TB and HIV coinfections among adult inmates with presumptive pulmonary TB in a Kenyan prison

BackgroundTuberculosis (TB) is more than ten times higher in prisons compared to the general population, and HIV-infected persons are at increased risk of developing active TB and death. In the World Health Organization (WHO) African region, however, where the TB and HIV coinfections are highest, and prisons rarely factored in national disease surveillance, epidemiological data to inform TB control interventions in correctional facilities is limited. In this study, we assessed the prevalence of TB and HIV coinfections, as well as the factors associated with coinfections in our study setting.MethodsThis was a prospective cross-sectional study among 157 adult (≥ 18 years) prisoners presenting with symptoms of pulmonary TB at Shimo La Tewa Prison, Kenya, between January and June 2023. The study excluded those with a history of anti-TB drugs use or on treatment follow-up and collected demographic and clinical characteristics data using a questionnaire. Sputum samples were collected and processed immediately using Xpert® MTB/RIF assay or stored at 4 °C for three (3) days in case of delay.ResultsThe overall prevalence of TB among inmates with presumptive pulmonary TB was 10.2%, 95% CI 6.37–16.91% (16/157), HIV 19.1%, 95% CI 13.73–25.97% (30/157). All the TB cases were positive for HIV (16/16, 100%), translating to TB/HIV coinfection of 10.2%, 95% CI 6.37–16.91% (16/157), and there was no rifampicin resistance. TB and HIV coinfection cases were found among underweight (100%, 16/16) prisoners. The independent factors associated with TB and HIV coinfections were education level (adjusted OR = 0.17, p = 0.007), smoking history (adjusted OR = 3.01, p = 0.009) and illegal drug use history (adjusted OR = 4.55, p = 0.044).ConclusionWe report a high prevalence of pulmonary TB and HIV coinfections among adult inmates with presumptive pulmonary TB in Kenya, with education level, smoking status, and illegal drug use as the independent factors associated with the coinfection. The authority should take measures to protect HIV-positive prisoners from TB, focusing on education, nutrition, smoking, and illegal drug use.

Laboratory data and broncho-alveolar lavage on Covid-19 patients with no intensive care unit admission: Correlation with chest CT features and clinical outcomes.

Broncho-alveolar lavage (BAL) is indicated in cases of uncertain diagnosis but high suspicion of Sars-Cov-2 infection allowing to collect material for microbiological culture to define the presence of coinfection or super-infection. This prospective study investigated the correlation between chest computed tomography (CT) findings, Covid-19 Reporting and Data System score, and clinical outcomes in Coronavirus disease 2019 (Covid-19) patients who underwent BAL with the aim of predicting outcomes such as lung coinfection, respiratory failure, and hospitalization length based on chest CT abnormalities. Study population included 34 patients (range 38-90 years old; 20 males, 14 females) with a positive nucleic acid amplification test for Covid-19 infection, suitable BAL examination, and good quality chest CT scan in the absence of lung cancer history. Pulmonary coinfections were found in 20.6% of patients, predominantly caused by bacteria. Specific correlations were found between right middle lobe involvement and pulmonary co-infections. Severe lung injury (PaO2/FiO2 ratio of 100-200) was associated with substantial involvement of right middle, right upper, and left lower lobes. No significant correlation was found between chest CT findings and inflammatory markers (C-reactive protein, procalcitonin) or hospitalization length of stay. Specific chest CT patterns, especially in right middle lobe, could serve as indicators for the presence of co-infections and disease severity in noncritically ill Covid-19 patients, aiding clinicians in timely interventions and personalized treatment strategies.

Empirical antibiotic therapy in COVID-19 ICU pulmonary coinfections

Empirical antibiotic therapy in COVID-19 ICU pulmonary coinfections

Management of pregnant women in tertiary maternity hospitals in the Paris area referred to the intensive care unit for acute hypoxaemic respiratory failure related to SARS-CoV-2: which practices for which outcomes?

BackgroundEvidence for the management of pregnant women with acute hypoxaemic respiratory failure (AHRF) is currently lacking. The likelihood of avoiding intubation and the risks of continuing the pregnancy under invasive ventilation remain undetermined. We report the management and outcome of pregnant women with pneumonia related to SARS-CoV-2 admitted to the ICU of tertiary maternity hospitals of the Paris area.MethodsWe studied a retrospective cohort of pregnant women admitted to 15 ICUs with AHRF related to SARS-CoV-2 defined by the need for O2 ≥ 6 L/min, high-flow nasal oxygen (HFNO), non-invasive or invasive ventilation. Trajectories were assessed to determine the need for intubation and the possibility of continuing the pregnancy on invasive ventilation.ResultsOne hundred and seven pregnant women, 34 (IQR: 30–38) years old, at a gestational age of 27 (IQR: 25–30) weeks were included. Obesity was present in 37/107. Intubation was required in 47/107 (44%). Intubation rate according to respiratory support was 14/19 (74%) for standard O2, 17/36 (47%) for non-invasive ventilation and 16/52 (31%) for HFNO. Factors significantly associated with intubation were pulmonary co-infection: adjusted OR: 3.38 (95% CI 1.31–9.21), HFNO: 0.11 (0.02–0.41) and non-invasive ventilation: 0.20 (0.04–0.80). Forty-six (43%) women were delivered during ICU stay, 39/46 (85%) for maternal pulmonary worsening, 41/46 (89%) at a preterm stage. Fourteen non-intubated women were delivered under regional anaesthesia; 9/14 ultimately required emergency intubation. Four different trajectories were identified: 19 women were delivered within 2 days after ICU admission while not intubated (12 required prolonged intubation), 23 women were delivered within 2 days after intubation, in 11 intubated women pregnancy was continued allowing delivery after ICU discharge in 8/11, 54 women were never intubated (53 were delivered after discharge). Timing of delivery after intubation was mainly dictated by gestational age. One maternal death and one foetal death were recorded.ConclusionIn pregnant women with AHRF related to SARS-CoV-2, HFNO and non-invasive mechanical ventilation were associated with a reduced rate of intubation, while pulmonary co-infection was associated with an increased rate. Pregnancy was continued on invasive mechanical ventilation in one-third of intubated women.Study registration retrospectively registered in ClinicalTrials (NCT05193526).

Pulmonary coinfection by Pneumocystis jirovecii and Aspergillus terreus in an ITP patient after corticosteroid therapy: A case report

AbstractPneumocystis jirovecii pneumonia and invasive pulmonary aspergillosis are both life‐threatening opportunistic fungal infections. There are only few reports of coinfection by these two fungi in the literature, and Aspergillus fumigatus is the predominant Aspergillus species in the coinfection. We report here the first case of coinfection by Aspergillus terreus and P. jirovecii pneumonia and caspofungin can be an appropriate choice for salvage treatment of the coinfection. A 51‐year‐old man with a history of immune thrombocytopenia treated with prednisone over 2 months was admitted to emergency intensive care unit for acute respiratory failure and a cavity was found on chest computed tomography. Therefore, his trachea was immediately intubated. The patient was treated with a large spectrum of antibiotic regimen, consisting initially of imipenem/cilastatin, moxifloxacin and fluconazole followed by fluconazole, imipenem/cilastatin, vancomycin, trimethoprim–sulphamethoxazole (TMP‐SMZ) and azithromycin. When the polymerase chain reaction analysis of the bronchoalveolar lavage sample revealed P. jirovecii and A. terreus, all the antibiotics were stopped except TMP‐SMZ, and voriconazole was added. Two weeks later, the patient showed clinical improvement but radiological deterioration. Consequently, caspofungin was started for salvage therapy, then the patient showed gradual clinical improvement. He was discharged with oral voriconazole and TMP‐SMZ. The antifungal treatment was continued for 6 months until complete radiological absorption. In conclusion, early bronchoscopy with bronchoalveolar lavage fluid should be considered in order to diagnose and treat promptly in those treated with corticosteroids combined with immunocompromised and caspofungin could be an appropriate choice for salvage treatment of coinfection by P. jirovecii and A. terreus.

Colliding Challenges: An Analysis of SARS-CoV-2 Infection in Patients with Pulmonary Tuberculosis versus SARS-CoV-2 Infection Alone.

Background and Objectives: The concurrent occurrence of tuberculosis and COVID-19 coinfection poses significant clinical complexities, warranting a nuanced approach to diagnosis, management, and patient care. Materials and Methods: A retrospective, cross-sectional study was conducted on two groups: one comprising 32 patients with pulmonary TB (PTB) and COVID-19 co-infection, and one including 100 patients with COVID-19 alone. Data was collected from medical records, including patient history, clinical parameters, laboratory, imaging results, and patient outcome. Results: A lower BMI emerges as a significant marker suggesting underlying PTB in patients with SARS-CoV-2 co-infection. Type 2 diabetes mellitus increases the risk of death in PTB-SARS-CoV-2 co-infection. Co-infected patients show lymphocytopenia and higher neutrophil levels, CRP, transaminases, and D-dimer levels. Elevated CRP and ALT levels are linked to increased co-infection likelihood. Certain parameters like SpO2, CRP, ALT, AST, and D-dimer effectively differentiate between co-infected and COVID-19 patients. Platelet-to-lymphocyte ratio is notably higher in co-infected individuals. Lesion severity on imaging is significantly associated with co-infection, highlighting imaging's diagnostic importance. Longer hospital stays are linked to co-infection but not significantly to death risk. Conclusions: Certain clinical and biological factors may serve as potential indicators of PTB co-infection in patients with SARS-CoV-2.

Pulmonary co-infections by Pneumocystis jirovecii and Herpesviridae: a seven-year retrospective study

BackgroundPneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary colonization in individuals with mild immunosuppression or impaired respiratory function. PCP and Cytomegalovirus (CMV) co-infections have been widely described whereas those involving other Herpesviruses (HVs) such as Epstein-Barr virus (EBV), Herpes simplex virus type 1 and type 2 (HSV-1 and -2), and Varicella zoster virus (VZV) remain scarce. To date, no data are available concerning HVs co-infections in P. jirovecii colonization.MethodsOur main objective was to evaluate the frequency of HVs in bronchoalveolar lavage fluid (BALF) samples from patients with PCP or with pulmonary colonization. The secondary objective was to assess the relationship between HVs and the mortality rate in PCP patients. A retrospective single-center study over a seven-year period was conducted. All patients with P. jirovecii detected using PCR in a BALF sample and for whom a PCR assay for HVs detection was performed were included in the study.ResultsOne hundred and twenty-five patients were included, corresponding to 77 patients with PCP and 48 colonized patients. At least one HV was detected in 54/77 (70.1%) PCP patients and in 28/48 (58.3%) colonized patients. EBV was the most frequent in both groups. Furthermore, the 30-day survival rate in PCP patients was significantly lower with [EBV + CMV] co-infection than that with EBV co-infection, [EBV + HSV-1] co-infection and without HV co-infection.ConclusionOur results show that the frequency of HV, alone or in combination is similar in PCP and colonization. They also suggest that [EBV + CMV] detection in BALF samples from PCP patients is associated with an increased mortality rate, underlying the significance to detect HVs in the course of PCP.

PERBANDINGAN CD4 HIV –TB PARU SEBELUM DAN SESUDAH ARV DAN OAT

Background: Human Immunodeficiency Virus (HIV) is a viral infectious disease that attacks the immune system or white blood cells (lymphocytes). HIV, which belongs to the Retroviridae family, is lymphatic, which can damage the specific immune system, namely T-helper lymphocytes or Cluster of Differentiation 4 (CD4). The CD4 count is normal when it is 500–1400 cells/mm3, which is usually the determinant of whether a patient is infected with HIV or not. Objective: This study aims to assess the comparison of CD4 counts in HIV-TB patients before and after ARV and OAT treatment at Dr. Pirngadi Medan City. Methods: Observational analysis research with a cross-sectional design was conducted at RSUD Dr. Pirngadi Medan City in September 2022. The sample for this study was 20 patient records from the medical records of RSUD Dr. Pirngadi, Medan City. The data were analyzed using an unpaired t-test. Results: The results of the study showed that the most HIV-TB pulmonary patients at RSUD Dr. Pirngadi Medan City were aged 36-45 years (50.0%). The majority of male patients (90.0%) and the domicile of most patients in Medan City are in the Medan Tembung sub-district (15.0%). The results of the unpaired t-test obtained a p-value of 0.022, meaning that there was a significant difference between the CD4 count before and after ARV and OAT treatment in HIV-TB patients at RSUD Dr. Pirngadi Medan City. Conclusion: There were significant differences in CD4 counts before and after ARV and OAT treatment in HIV patients with pulmonary TB co-infection at Dr. Pirngadi, Medan City. Keywords: HIV, HIV-TB pulmonary, CD4

Prevalence of Pulmonary Tuberculosis and HIV Co-Infection among Women in Bogodogo, Burkina Faso

Prevalence of Pulmonary Tuberculosis and HIV Co-Infection among Women in Bogodogo, Burkina Faso

ОСОБЕННОСТИ ПРОЯВЛЕНИЙ ВПЕРВЫЕ ВЫЯВЛЕННОГО ТУБЕРКУЛЕЗА ОРГАНОВ ДЫХАНИЯ У БОЛЬНЫХ С СОПУТСТВУЮЩИМИ ВИРУСНЫМИ ГЕПАТИТАМИ

Objective: to study typical manifestations of newly diagnosed pulmonary TB in patients with viral hepatitis (VH) co-infection. Materials and methods. The cohort cross-sectional study included 35 patients with newly diagnosed pulmonary TB; out of them 15 patients had pulmonary TB and hepatitis virus C or B co-infection (group 1) and 20 patients had pulmonary TB alone (group 2). The study was carried out in 2019–2023. Results. Among patients with TB/VH co-infection men aged 50–59 and women aged 60–69 years either with unhealthy habits (including alcohol and substance abuse), or ex-prisoners, or those burdened with comorbidities (gastrointestinal diseases, cardiovascular diseases, type 2 diabetes mellitus) prevailed. In these patients we commonly observed tuberculomas, small destructive changes, and preserved susceptibility to TB drugs. Conclusion. Among patients with pulmonary TB and VH co-infection men aged 50–59 and women aged 60–69 years with unhealthy habits or underlying gastrointestinal or cardiovascular disease or type 2 diabetes mellitus prevailed. The typical manifestations of pulmonary TB in this category of patients were pulmonary tuberculoma, small destructive changes, and preserved susceptibility to TB drugs. Before TB treatment commencement the patients with pulmonary TB and VH co-infection had elevated aminotransferase levels, enlarged liver with signs of fibrosis.

Resistant Pulmonary TB-HIV Co-Infection in an Infant: About a Case

Resistant Pulmonary TB-HIV Co-Infection in an Infant: About a Case

Asymptomatic pulmonary co-infection with Cryptococcus and Aspergillus in a patient from China

n asymptomatic HIV-negative patient was admitted to hospital because she was found multiple pulmonary nodules by chest Computed Tomography (CT) in a routine examination. And the patient was diagnosed as pulmonary cryptococcosis and aspergillosis

Impact of the COVID-19 Pandemic on the Epidemiological Situation of Pulmonary Tuberculosis-Using Natural Language Processing.

We aimed to analyze the impact of the COVID-19 pandemic on pulmonary tuberculosis (TB) using artificial intelligence. To do so, we compared the real-life situation during the pandemic with the pre-2020 situation. This non-interventional, retrospective, observational study applied natural language processing to the electronic health records of the Castilla-La Mancha region of Spain. The analysis was conducted from January 2015 to December 2020. A total of 2592 patients were diagnosed with pulmonary tuberculosis; 64.6% were males, and the mean age was 53.5 years (95%CI 53.0-54.0). In 2020, pulmonary tuberculosis diagnoses dropped by 28% compared to 2019. In total, 62 (14.2%) patients were diagnosed with COVID-19 and pulmonary tuberculosis coinfection in 2020, with a mean age of 52.3 years (95%CI 48.3-56.2). The main symptoms in these patients were dyspnea (27.4%) and cough (35.5%), although their comorbidities were no greater than patients with isolated TB. The female sex was more frequently affected, representing 53.4% of this patient subgroup. During the first year of the COVID-19 pandemic, a decrease was observed in the incidence of pulmonary tuberculosis. Women presented a significantly higher risk for pulmonary tuberculosis and COVID-19 coinfection, although the symptoms were not more severe than patients diagnosed with pulmonary tuberculosis alone.

Model of Pulmonary Co-Infection of Aspergillus and Pseudomonas in Immunocompetent Mice

Co-infection with Pseudomonas (Pa) and Aspergillus (Af) commonly occurs in the airways of immune-compromised patients or in cystic fibrosis and frequently results in more severe outcomes than mono-infection. We affixed both pathogens to agar beads, separately (Af beads, Pa beads) or on the same bead (AfPa beads) and infected immunocompetent mice, an in vivo Af-Pa interaction model. Endotracheal administration was superior to intranasal, allowing larger beads to be administered resulting in longer lung residence. The CFU of the Af beads, diameter 150–250 µm, were detectable for ≤21 days. Af-bead-infected mice cleared the Af infection more than mice infected with AfPa beads, but Af clearance was the same with a combination of beads (Af beads + Pa beads). Pa-infected mice had more Pa clearance in the presence of Af than with Pa beads alone. In vitro studies supported our conclusion that the close proximity of Af and Pa (on AfPa beads) was disadvantageous for Af, whereas a larger distance (Af + Pa beads) was not. We demonstrated that the interaction between Pseudomonas and Aspergillus during co-infection can be studied in immunocompetent mice. The mutual inhibition of Af and Pa in vivo appears to be dependent on their proximity. We review the literature relating to animal models of infection with Af, Pa, or both.

Asymptomatic Pulmonary Cryptococcosis And Tuberculosis Co-infection in an immunocompetent Host: A case report

Pulmonary Cryptococcosis is a rare fungal infection that mostly occurs in immunocompromised host. However, with advancement in diagnostic approach like tissue biopsy, cryptococcal infections are now increasingly being recognised.In immunocompetent host, cryptococcal infection is often asymptomatic and rarely becomes disseminated.
 Symptom development in immunocompetent host largely depends on burden and virulence of pathogen. Due to similarities in clinical, radiological and pathological findings in Cryptococcosis, Tuberculosis and other fungal infections like Blastomycocosis, it is important to have a tissue biospy to confirm the diagnosis.
 The aim of this case report is to highlight the investigation necessary to diagnose both fungal infection and Tuberculosis due to similar clinical, radiological features in both. We report a case of Gene Xpert positive Tuberculosis and histopathology proven Pulmonary Cryptococcos in same patient.

Sub-therapeutic trimethoprim and sulfamethoxazole plasma concentrations during continuous venovenous hemofiltration in a patient with COVID-19 and pulmonary Pneumocystis jirovecii co-infection: Acase report.

To investigate drug concentration of trimethoprim-sulfamethoxazole (TMP-SMX) using therapeutic drug monitoring (TDM) for severe Pneumocystis jirovecii (PJP) infection in a critically ill patient with COVID-19 receiving continuous venovenous hemofiltration treatment and regional citrate anticoagulation (RCA-CCVH). A 72-year-old man with hypoxemic respiratory failure due to COVID-19 infection was admitted to the intensive care unit for invasive mechanical ventilation. The patient developed acute renal failure that required RCA-CVVH. Pulmonary co-infection with PJP was diagnosed, and a high TMP-SMX dose was initiated according to (inter)national guidelines with dose reduction after 3 days because of renal failure. Population pharmacokinetics were assessed for TMP and SMX as well as clearance by RCA-CVVH, volume of distribution, and time above threshold levels for measured plasma concentrations. During renal failure requiring RCA-CVVH, a corresponding dose reduction of TMP-SMX to 320/1,600 mg twice a day, according to current Dutch SWAB and Dutch Association of Hospital Pharmacists guidelines, resulted in unintended under-dosing with sub-therapeutic TMP-SMX concentrations. Pharmacokinetic modeling and dose adjustment of TMP-SMX to 640/3,200 mg 3 times daily resulted in steady-state TMP-SMX peak concentrations associated with efficacy against PJP. Hence, the patient was successfully weaned from the ventilator and discharged. We hypothesize that our new dose recommendation of 640/3,200 mg TMP-SMX 3 times daily is associated with an increased probability of critical patients being successfully liberated from mechanical weaning following PJP pneumonia and COVID-19 infection.