Trimethoprim-sulfamethoxazole (TMP-SMX) is the preferred prophylactic agent for Pneumocystis jiroveci pneumonia (PJP) and toxoplasmosis after solid organ transplant (SOT). Compared with other agents, it has additional activity against Nocardia species.

The purpose of this study was to evaluate the incidence of Nocardia infection in SOT patients receiving TMP-SMX or an alternative agent for opportunistic infection (OI) prophylaxis.

This retrospective analysis included transplant recipients at a large urban medical center over a period of 4 years. All patients received either TMP-SMX or an alternative agent for PJP prophylaxis. The primary outcome was the incidence of Nocardia infection within 24 months posttransplant. Secondary outcomes included resistance rates of Nocardia isolates, usage rates of alternative prophylactic agents, reasons for using alternative agents, and rate of conversion from an alternative agent back to TMP-SMX.

A total of 791 adult SOT recipients who received PJP or toxoplasmosis prophylaxis were included. Mean age at transplantation was 60.9 years with the majority of patients being male (67.3%) lung transplant recipients (63.6%). TMP-SMX was the most commonly used initial prophylactic agent (84.6%), followed by atovaquone (15.4%). Of the 791 SOT recipients, 16 (2.0%) were diagnosed with nocardiosis within 24 months posttransplant. Patients receiving alternative agents had a higher incidence of infection compared with those receiving TMP-SMX prophylaxis (P < 0.001).

Our findings suggest that OI prophylaxis with TMP-SMX may be protective against nocardiosis in SOT recipients. If possible, patients who are switched to an alternative agent due to TMP-SMX intolerance should be re-challenged when the adverse effect resolves. Most patients in our study were able to tolerate re-initiation, suggesting that the adverse effects associated with TMP-SMX may be temporary and may not warrant discontinuation.

Liver transplant (LT) recipients have a profound susceptibility to infections. Although Nocardia and Actinomyces (NAs) are well-known bacteria that typically affect immunosuppressed patients, a scarcity of research exists on the effects of LT with NA infections. Our study aims to evaluate the outcomes associated with NA infections in patients with LT. Patients were selected from the National Inpatient Sample (NIS) from 2008 through 2020. International Classification of Disease revision 9 (ICD-9) and ICD revision 10 (ICD-10) codes. Patients admitted with a history of LT were subdivided into those who were and were not diagnosed with an NA infection. Records were weighted using the NIS algorithm. Primary outcomes were all-cause hospital mortality, acute kidney injury (AKI), acute myocardial infarction (AMI), shock, and a composite of these. Secondary outcomes were length of stay, total charges, cytomegalovirus (CMV), and transplant rejection. Demographics and comorbidities were compared between the groups with a weighted chi-square test. Outcomes were compared between the two groups, and adjusted odds ratios (ORs) and regression coefficients were calculated using weighted logistic or linear regression as appropriate. ORs were adjusted for age, gender, race, hospital characteristics, Charlson Comorbidity Index (CCI), median income based on zip code, weekend admission, and insurance. There were 469,141 patients with LT who were included in this study, 310 of them had NA infection (0.07%). Patients in each group were of similar age, race, and overall medical complexity (P > .05). Patients with NA infection were less likely to have a history of coronary artery disease (CAD; 4.84% vs 16.20%, P < .05), hypertension (14.53% vs 25.82%, P < .05), and obesity (1.61% vs 9.0%, P < .05) than the healthy controls. Patients with LT with NA infection were found to have higher odds of mortality (OR = 5.50, P < .001), AKI (OR = 1.9, P < .05), composite outcome (OR = 2.19, P < 0.01), and more likely to have CMV infection (OR = 6.38, P < .01). Patients with LT with NA infection stayed 13.11 days longer in the hospital (P < .01) with charges of $60,399 more (P < .01) than the healthy controls. Patients with LT who acquired an NA infection were at nearly six-fold higher odds of death and other negative outcomes. Based on previous research that has demonstrated organ transplant patients to be at high risk of infections, more vigilant care should be taken to protect patients with LT from such opportunistic infections.

Nocardiosis is an uncommon yet potentially devastating infection. Nocardia tends to affect individuals with chronic lung disease or immunocompromising conditions, 2 groups increasing in number. Incidence of nocardiosis is likely to increase as well, and it is vital to have an approach to this complex disease. Here, we aim to review the presentation, diagnosis, and management of Nocardia in the modern era. We will also highlight areas of uncertainty in our understanding of nocardiosis and propose a general approach to nocardiosis therapy, accounting for response and tolerance of Nocardia treatment.

Nocardia farcinica is a virulent organism known for its high resistance to many antibiotics and its ability to cause disseminated life-threatening infections, particularly in immunocompromised patients or those undergoing organ transplantation. Candida albicans can cause disseminated candidiasis with a mortality rate ranging from 30% to 60%. Cases involving concurrent disseminated N. farcinica and C. albicans, particularly in patients with autoimmune thrombocytopenia, are extremely rare. The presence of two disseminated pathogens complicates both diagnosis and treatment, creating substantial challenges for healthcare providers.

A 50-year-old woman who had a history of autoimmune thrombocytopenia and was being treated with prednisone (60 mg qd). She presented with a 40-day history of high-grade fevers (40℃), cough, headache, and multiple abscesses in the skin structure. N. farcinica was found in her skin structure, cerebrospinal fluid, and blood, and C. albicans was cultured in cerebrospinal fluid, sputum, and urine. She was diagnosed with disseminated nocardiosis and disseminated candidiasis. The patient received a prolonged course of multiple anti-bacterial and anti-fungal medications and eventually recovered.

Due to the atypical clinical presentations, the diagnosis of concurrent invasive disseminated N. farcinica and C. albicans infections might be delayed. A variety of diagnostic testing, including metagenomics next-generation sequencing, can help to identify the pathogen rapidly. Drug susceptibility test can guide the selection and adjustment of antibiotics, which should be in companion with surgical interventions to save lives in affected patients.

Morbidity and mortality rates after lung transplantation still remain higher than after other forms of solid organ transplantation, primarily due to a higher risk of infections and the development of chronic lung allograft dysfunction. Thus, a tiered approach highlighting the most significant respiratory pathogens including common opportunistic infections along with diagnostic, treatment and prevention strategies, including vaccination and prophylaxis is needed.

The need for intense immunosuppressive therapy to prevent rejection, coupled with the transplanted lung's constant exposure to environment and impaired local defence mechanisms leads to frequent infections. Viral and bacterial infections are most frequent while fungal infections mainly involve the tracheobronchial tract but may be fatal in case of disseminated disease. Some infectious agents are known to trigger acute rejection or contribute to chronic allograft dysfunction. Invasive testing in the form of bronchoscopy with bronchoalveolar lavage is standard and increasing experience in point of care testing is gained to allow early preemptive therapy.

Timely diagnosis, treatment, and ongoing monitoring are essential, but this can be difficult due to the wide variety of potential pathogens.

Nocardia species are aerobic, Gram-positive actinomycetes often causing opportunistic infections, particularly in immunocompromised hosts. Nocardia farcinica is notable for disseminated nocardiosis (DN), frequently involving the lungs and central nervous system (CNS). Cushing's syndrome (CS), characterized by hypercortisolemia, further predisposes patients to severe infections. We report a 73-year-old woman with ACTH-dependent CS due to a pituitary adenoma who developed DN with pleuropulmonary, CNS, and gluteal abscesses. Diagnosis was confirmed through cultures and MALDI-TOF MS, identifying N. farcinica. Resistance to standard antibiotics required a tailored regimen, including imipenem, amikacin, and moxifloxacin, alongside surgical management of abscesses and the adenoma. This case emphasizes the importance of rapid diagnostic methods and individualized therapies in managing DN with CS, a rare but severe combination. It highlights the need for vigilance in high-risk patients and contributes valuable insights for optimizing outcomes in such complex cases.

A 28-year-old male presented to an Australian hospital with sudden-onset headache and seizure following a kidney transplant for end-stage renal disease due to IgA nephropathy. Clinical approach to the cases and management of the diagnosed disease are discussed.

Linezolid is an oxazolidinone antibiotic that is mainly permitted to treat Gram-positive bacterial infections. Recent studies have shown that linezolid also has antibacterial effects on several other bacteria outside the package insert, including Mycobacterium tuberculosis, non-tuberculous mycobacteria (NTM), Nocardia, Corynebacterium, and anaerobes, etc. Interestingly, linezolid also has an in vitro inhibitory effect on fungi. This review focuses on the in vitro antibacterial activity of linezolid against microorganisms outside its antibacterial spectrum. We mainly listed the number of the tested strains, the minimum inhibitory concentration (MIC) range, MIC50, and MIC90 of linezolid against those pathogens outside the package insert. The results showed that among these tested pathogens, linezolid displayed strong inhibitory effects against M. tuberculosis, Nocardia, and Corynebacterium, with an MIC range of ≤2 μg/mL. As for NTM, linezolid exhibited moderate to potent inhibitory effects against the strains of different species with an MIC range of 0.06-128 μg/mL. Moreover, linezolid was reported to have a species-dependent inhibitory effect on anaerobes at a concentration range of 0.003-16 μg/mL. Furthermore, linezolid could enhance azoles and amphotericin B's antifungal activity on Candida synergistically. It is hoped that this analysis can provide data for expanding the application of linezolid, make the off-label drug use have more compelling evidence, and provide clues for the development of new drugs.

The aim of the study was to study the clinical profile and outcomes of nocardiosis in renal allograft recipients.

This was a retrospective study of clinical outcomes in consecutive renal allograft recipients with Nocardia infection over a 22-year period (2000-2022) from a tertiary care center in Southern India. The clinical data were obtained from electronic medical records and patient files.

A total of 1970 patients underwent renal transplantation at Christian Medical College, Vellore, India, between January 1, 2000, and December 31, 2022. During this period, 26 patients were diagnosed to have Nocardia infection. Half (50%) of the patients had fever and cough as their initial presentation, 7 (26.9%) patients presented with cutaneous abscesses, 2 (7.6%) patients were incidentally detected to have lung nodules during routine follow-up, 2 (7.6%) patients presented with headache accompanied by fever, and 3.8% had graft abscess. The diagnosis was made by isolating the organism in culture from one or more of the following samples: sputum, blood, pus, or lung biopsy (either computed tomography [CT]-guided or bronchoscopic aspirate culture). Eight patients required bronchoscopy and two patients required CT-guided biopsy for obtaining samples for diagnosis. All patients were similarly managed initially with a reduction of immunosuppression and appropriate antibiotics as per culture sensitivity. All 26 patients responded to induction treatment with meropenem (or imipenem) and trimethoprim-sulfamethoxazole (co-trimoxazole) followed by maintenance treatment with co-trimoxazole. Five (19.2%) out of 26 patients received Minocycline in induction and maintenance treatment regimens as in four patients isolates were resistant and one patient had allergic reaction to Cotrimoxazole. All patients had stable graft function. Two patients succumbed after 2 months of diagnosis with Gram-negative sepsis.

At present, there exists no single serological test to diagnose Nocardia infection in patients. Multiple initially obtained cultures may be negative because of the slow growth of the organism and variable colony morphology. Hence, infected specimens should be obtained by aggressive approaches if the index of suspicion is high. Procedures such as bronchoscopic lavage and aspiration of abscess are invaluable toward making a diagnosis. In our study, eight patients required invasive diagnostic procedures such as bronchoalveolar lavage and CT-guided lung biopsy since initial Gram stain and sputum culture were negative. In conclusion, it is crucial to maintain a high level of suspicion and conduct thorough investigations among post renal transplant recipients. This approach facilitates early diagnosis, prompt initiation of appropriate treatment which helps prevent the spread of disease.

Nocardia, a rare but potentially fatal pathogen, can induce systemic infections with diverse manifestations. This study aimed to investigate the tissue and organ damage caused by Nocardia farcinica (N. farcinica) in mice via different infection routes, evaluate the resulting host immune responses, and assess its invasiveness in brain tissue.

BALB/c mice were infected with N. farcinica through intranasal, intraperitoneal, and intravenous routes (doses: 1 × 10^8, 1 × 10^7, 1 × 10^7 CFU in 50 µl PBS). Over a 7-day period, body temperature, weight, and mortality were monitored, and samples were collected for histopathological analysis and bacterial load assessment. Serum was isolated for cytokine detection via ELISA. For RNA-seq analysis, mice were infected with 1 × 107 CFU through three infection routes, after which brain tissue was harvested.

Intraperitoneal and intravenous N. farcinica infections caused significant clinical symptoms, mortality, and neural disruption in mice, resulting in severe systemic infection. Conversely, intranasal infection primarily affected the lungs without causing significant damage to other organs. Intraperitoneal and intravenous infections significantly increased serum cytokines, particularly TNF-α and IFN-γ. RNA-seq analysis of brains from intravenously infected mice revealed significant differential gene expression, whereas the intranasal and intraperitoneal routes showed limited differences (only three genes). The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the intravenous group were primarily related to immune processes.

The study demonstrated that intravenous N. farcinica infection induces significant clinical symptoms, triggers an inflammatory response, damages multiple organs, and leads to systemic infections.

Nocardia farcinica is an aerobic gram-positive bacterium that is pathogenic to humans. It usually causes local and adjacent tissues' diseases at the entry of infection (most commonly occur in the lungs, skin, or central nervous system), which can also spread to other organs through the bloodstream such as joints, kidneys, and liver. However, these infections are often seen as opportunistic that occur in immunocompromised patients. Here, we report for the first time two immunocompetent patients lacking evidence of local infections, with multiple lymph node enlargements and fever as main clinical manifestations, finally diagnosed as nocardiosis by Metagenomic Next-Generation Sequencing testing (mNGS) from formalin-fixed and paraffin-embedded (FFPE) lymph node tissue, after all the other standard tests were negative. Both patients recovered after receiving anti-nocardia therapies. These two cases indicates that in healthy population, there may be more potential nocardia infections than we expected. Multiple lymph node enlargements and fever suggest a possibility of nocardiosis, especially in patients with fever of unknown origin (FUO). mNGS detection from FFPE lymph node tissue is an accurate, reliable and traceable method for diagnosis of nocardiosis.

How to cite this article: Khilnani GC, Tiwari P, Mittal S, Kulkarni AP, Chaudhry D, Zirpe KG, et al. Guidelines for Antibiotics Prescription in Critically Ill Patients. Indian J Crit Care Med 2024;28(S2):S104-S216.

Suppurative thyroiditis is a rare entity with a low incidence in thyroid diseases, manifesting with pain, fever, dysphagia, and dysphonia. Its infrequency is explained by the thyroid gland's resistance to infections due to its encapsulated position, high blood flow, bactericidal action of iodine, and extensive lymphatic network. We present the first report in the literature of a 72-year-old woman with a history of inflammatory myopathy and immunosuppression diagnosed with suppurative thyroiditis co-infected with Nocardia spp. and Mycobacterium tuberculosis. This entity requires a high clinical suspicion, and fine-needle aspiration biopsy (FNAB) is preferred as the diagnostic method for microbiological sampling. Although rare, it carries high morbidity and mortality if not suspected in time.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated motor sensory peripheral neuropathy that is rare in clinical practice. This treatment method aims to suppress potential immunopathology. Nocardiosis is a rare, destructive, opportunistic disease. We report a case of failed treatment of CIDP combined with pulmonary nocardiosis, and for the first time, we link these 2 diseases together.

A 65-year-old man developed symmetrical limb weakness. Four months later, he was diagnosed with CIDP and started receiving glucocorticoid (GC) treatment. The disease progressed slowly and was treated with mycophenolate mofetil (MMF) in combination. He did not follow the doctor requirements for monthly follow-up visits, and the preventive medication for sulfamethoxazole/trimethoprim was not strictly implemented. Two months after the combination therapy, the patient developed fever, coughing and sputum production, as well as fatigue and poor appetite. Based on imaging and etiological results, he was diagnosed with pulmonary nocardiosis.

Chronic inflammatory demyelinating polyneuropathy, pulmonary nocardiosis.

After treatment with antibiotics, the patient lung infection temporarily improved. However, the patient CIDP condition progressed, limb weakness worsened, respiratory muscle involvement occurred, and intravenous immunoglobulin (IVIG) was administered. However, there was no significant improvement in the condition, and the patient died.

In this report, we present a case of a patient with CIDP and pulmonary nocardiosis. It is worth noting that in order to avoid the progression and recurrence of CIDP, we did not stop using related therapeutic drugs during the treatment process, the patient had repeatedly refused to use IVIG. Despite this, the patient condition worsened when lung inflammation improved, leading to persistent respiratory failure and ultimately death. Treatment contradictions, medication issues, and patient compliance issues reflected in this case are worth considering.

For patients with CIDP receiving immunosuppressive therapy, attention should be paid to the occurrence and severity of Nocardia infection. Therefore, early detection and treatment are necessary. We need to pay attention to the compliance of patients with prophylactic use of antibiotics, strengthen the follow-up, and urge them to return to their appointments on time.

Solid organ transplant recipients (SOTRs) are at an increased risk of nocardiosis, a rare but life-threatening opportunistic infection. Universal PCP prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) is used at our center, which is active in vitro against most species of the Nocardia genus and may have a role in preventing early infections. This is a single-center retrospective cohort study of nocardiosis in adult SOTRs at a large transplant center between January 2012 and June 2022, with comprehensive review of literature. Out of 6179 consecutive cases, 13 (0.2%) were diagnosed with nocardiosis. The patients were predominantly male (76.9%) and kidney transplant recipients (62%). Infection was diagnosed at median of 8.8 months (range, 3.7-98) after transplant. Patients were followed for a median of 457 days (range 8-3367). Overall mortality within one year after diagnosis was 46% (6/13), of which 17% (1/6) of deaths was attributable to Nocardia infection. No recurrence was reported. Nocardia infections were noted in a small proportion of our SOTRs and carried significant morbidity and mortality. TMP-SMX prophylaxis may be protective in some cases given low incidence of cases.

Kidney transplant recipients are at increased risk of opportunistic infections, including Nocardia. The incidence of nocardiosis in kidney transplant recipients is 0.4-1.3%. The data regarding its epidemiology and outcomes is limited.

This was a 10-year retrospective observational study from January 2012 to December 2021 at a tertiary care center in northern India, in which all kidney transplant recipients with Nocardia infection were included and followed.

12 (1.1%) patients had a Nocardia infection among the 1108 kidney transplant recipients. All were living donor kidney transplant recipients, and the mean age at diagnosis was 48.67 ± 12.60 years. Nocardia infection occurred at a median of 26 months (range 4-235) post-transplantation, with 4 (33.1%) of the cases occurring within a year of transplant. Breakthrough infection occurred in 7 (58.3%) patients on cotrimoxazole prophylaxis. 41.7% (n = 5) cases had an episode of rejection in the preceding year of Nocardia diagnosis. Concurrent cytomegalovirus (CMV) infection was present in one (8.3%) case. The lung was the most frequently involved organ. Microscopy was positive in all the cases; while culture was positive in 10 cases, and antimicrobial susceptibility testing (AST) were performed for these isolates. The majority (60%) of isolates were resistant to cotrimoxazole. All tested isolates remained susceptible to Amikacin, Imipenem, and Linezolid. No patients experienced Nocardia recurrence after completion of antibiotic therapy. The mortality at 12 months was 66.7% (n = 4), and only one death was Nocardia-related.

Nocardia may cause a late-manifesting infection beyond the traditional window. The cotrimoxazole prophylaxis may not be sufficient for Nocardia prevention.

Central nervous system (CNS) infections in solid organ transplant (SOT) recipients may present atypical or nonspecific symptoms. Due to a wider range of infectious agents compared with immunocompetent hosts, diagnosis is challenging. This review categorizes CNS infections in SOT recipients by cause.

New studies have reported new data on the epidemiology and the risk factors associated with each specific pathogen described in this review. Additionally, we included the treatment recommendations.

The latest findings give us an insight into the different pathogens causing infectious neurologic complications in SOT recipients.

Lung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off-label use of letermovir (LET) may avert myelotoxicity associated with valganciclovir (VGCV), but data in lung transplantation are limited. This study aims to evaluate the outcomes of LET prophylaxis among lung transplant recipients.

This retrospective, matched cohort study included lung transplant recipients who received LET for primary CMV prophylaxis following VGCV intolerance. Patients were matched 1:1 to historical VGCV controls based on age, serostatus group, and time from transplant. The primary outcome was CMV breakthrough within 1 year post-LET initiation; secondary outcomes included hematologic changes.

A total of 124 lung transplant recipients were included per group (32% CMV mismatch, D+R-), with LET initiated a median of 9.6 months post-transplantation. One CMV breakthrough event (0.8%) was observed in the LET group versus four (3.2%) in the VGCV group (p = .370). The median (interquartile range) white blood cell (WBC) count was 3.1 (2.1-5.6) at LET initiation which increased to 5.1 (3.9-7.2) at the end of follow-up (p <.001). For VGCV controls, WBC was 4.8 (3.4-7.2) at baseline and 5.4 (3.6-7.2) at the end of follow-up; this difference was not statistically significant (p = .395). Additionally, 98.4% of LET patients experienced ≥1 leukopenia episode in the year prior to LET compared to 71.8% the year after initiation (p <.001). Similar results were observed for neutropenia (48.4% and 17.7%, p <.001).

LET prophylaxis was associated with a low rate of CMV reactivation and leukopenia recovery. LET may represent a reasonable prophylaxis option for lung transplant recipients unable to tolerate VGCV.

Nocardiosis is a rare but life-threatening infection after hematopoietic cell transplantation (HCT). We aimed at identifying risk factors for nocardiosis after allogeneic HCT and clarifying the effect of trimethoprim-sulfamethoxazole prophylaxis on its occurrence.

We performed a retrospective multicenter case-control study of patients diagnosed with nocardiosis after allogeneic HCT between January 2000 and December 2018. For each case, two controls were matched by center, transplant date, and age group. Multivariable analysis was conducted using conditional logistic regression to identify potential risk factors for nocardiosis. Kaplan-Meier survival curves of cases and controls were compared using log-rank tests.

Sixty-four cases and 128 controls were included. Nocardiosis occurred at a median of 9 months after allogeneic HCT (interquartile range: 5-18). After adjustment for potential confounders in a multivariable model, Nocardia infection was associated with tacrolimus use (adjusted odds ratio [aOR] 9.9, 95 % confidence interval [95 % CI]: 1.6-62.7), lymphocyte count < 500/µL (aOR 8.9, 95 % CI: 2.3-34.7), male sex (aOR 8.1, 95 % CI: 2.1-31.5), recent use of systemic corticosteroids (aOR 7.9, 95 % CI: 2.2-28.2), and recent CMV infection (aOR 4.3, 95 % CI: 1.2-15.9). Conversely, use of trimethoprim-sulfamethoxazole prophylaxis was associated with a significantly decreased risk of nocardiosis (aOR 0.2, 95 % CI: 0.1-0.8). HCT recipients who developed nocardiosis had a significantly decreased survival, as compared with controls (12-month survival: 58 % and 90 %, respectively; p < 0.0001).

We identified six factors independently associated with the occurrence of nocardiosis among allogeneic HCT recipients. In particular, trimethoprim-sulfamethoxazole prophylaxis was found to protect against nocardiosis.

This is a case of a kidney transplant recipient who presented with skin lesions, low-grade fevers, and pancytopenia 2 months after his transplant.

Nocardia tends to cause infection in immunocompromised patients or those with chronic pulmonary disease. Nocardia is known to recur, prompting the practice of secondary prophylaxis in patients perceived at high risk. However, few data exist regarding the epidemiology of recurrent nocardiosis or the effectiveness of secondary prophylaxis.

We performed a multicenter, retrospective cohort study of adults diagnosed with nocardiosis from November 2011 to April 2022, including patients who completed primary treatment and had at least 30 days of posttreatment follow-up. Propensity score matching was used to analyze the effect of secondary prophylaxis on Nocardia recurrence.

Fifteen of 303 (5.0%) patients developed recurrent nocardiosis after primary treatment. Most recurrences were diagnosed either within 60 days (N = 6/15, 40.0%) or between 2 to 3 years (N = 4/15, 26.7%). Patients with primary disseminated infection tended to recur within 1 year, whereas later recurrences were often nondisseminated pulmonary infection. Seventy-eight (25.7%) patients were prescribed secondary prophylaxis, mostly trimethoprim-sulfamethoxazole (N = 67/78). After propensity-matching, secondary prophylaxis was not associated with reduced risk of recurrence (hazard ratio, 0.96; 95% confidence interval, .24-3.83), including in multiple subgroups. Eight (53.3%) patients with recurrent nocardiosis required hospitalization and no patients died from recurrent infection.

Recurrent nocardiosis tends to occur either within months because of the same Nocardia species or after several years with a new species. Although we did not find evidence for the effectiveness of secondary prophylaxis, the confidence intervals were wide. However, outcomes of recurrent nocardiosis are generally favorable and may not justify long-term antibiotic prophylaxis for this indication alone.

Background: Liver transplant recipients often require endoscopic retrograde cholangiopancreatography (ERCP) for biliary complications, which can lead to infections. This retrospective single-center study aimed to identify risk factors for infectious complications following ERCP in liver transplant patients. Methods: A retrospective analysis was conducted on 285 elective ERCP interventions performed in 88 liver transplant patients at a tertiary care center. The primary endpoint was the occurrence of an infection following ERCP. Univariable and multivariable regression analyses, Cox regression, and log-rank tests were employed to assess the influence of various factors on the incidence of infectious complications. Results: Among the 285 ERCP interventions, isolated anastomotic stenosis was found in 175 cases, ischemic type biliary lesion (ITBL) in 103 cases, and choledocholithiasis in seven cases. Bile duct interventions were performed in 96.9% of all ERCPs. Infections after ERCP occurred in 46 cases (16.1%). Independent risk factors for infection included male sex (OR 24.19), prednisolone therapy (OR 4.5), ITBL (OR 4.51), sphincterotomy (OR 2.44), cholangioscopy (OR 3.22), dilatation therapy of the bile ducts (OR 9.48), and delayed prophylactic antibiotic therapy (>1 h after ERCP) (OR 2.93). Additionally, infections following previous ERCP interventions were associated with an increased incidence of infections following future ERCP interventions (p < 0.0001). Conclusion: In liver transplant patients undergoing ERCP, male sex, prednisolone therapy, and complex bile duct interventions independently raised infection risks. Delayed antibiotic treatment further increased this risk. Patients with ITBL were notably susceptible due to incomplete drainage. Additionally, a history of post-ERCP infections signaled higher future risks, necessitating close monitoring and timely antibiotic prophylaxis.

Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial.

To assess the effect of TMP-SMX in the prevention of nocardiosis after SOT, its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection.

A systematic review and individual patient data meta-analysis.

MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, and Scopus up to 19 September 2023.

(a) Risk of nocardiosis between SOT recipients with and without TMP-SMX prophylaxis, or (b) sufficient details to determine the rate of TMP-SMX resistance in breakthrough nocardiosis.

SOT recipients.

TMP-SMX prophylaxis versus no prophylaxis.

Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies.

For our primary outcome (i.e. to determine the effect of TMP-SMX on the risk of nocardiosis), a one-step mixed-effects regression model was used to estimate the association between the outcome and the exposure. Univariate and multivariable unconditional regression models were used to adjust for the potential confounding effects. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Individual data from three case-control studies were obtained (260 SOT recipients with nocardiosis and 519 uninfected controls). TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18-0.52, moderate certainty of evidence). Variables independently associated with an increased risk of nocardiosis were older age, current use of corticosteroids, high calcineurin inhibitor concentration, recent acute rejection, lower lymphocyte count, and heart transplant. Breakthrough infections (66/260, 25%) were generally susceptible to TMP-SMX (pooled proportion 98%, 95% CI 92-100).

In SOT recipients, TMP-SMX prophylaxis likely reduces the risk of nocardiosis. Resistance appears uncommon in case of breakthrough infection.

Background This study aimed to present the clinical and radiological characteristics and the outcomes of patients with Nocardia infection of the central nervous system (CNS). Methodology We conducted a retrospective review of patients aged 18 and older admitted between August 1998 and November 2018 with culture-proven nocardiosis and CNS involvement. Results Out of 110 patients with nocardiosis, 14 (12.7%) patients had CNS involvement. The median age was 54.5 (27, 86) years, and 12 (85.7%) patients were male. Overall, 12 (85.7%) patients were immunosuppressed on high doses of glucocorticoids; seven (50%) patients were solid organ transplant recipients. Only eight (57.1%) patients had neurological symptoms at presentation, and the rest were diagnosed with CNS involvement after imaging surveillance. Three distinct radiologic patterns were identified, namely, single or multiple abscesses, focal cerebritis, and small, septic embolic infarcts. All isolates of Nocardia were susceptible to trimethoprim/sulfamethoxazole and amikacin, with susceptibility to linezolid and carbapenems being 90.9% and 79.5%, respectively. Despite receiving antibiotic therapy, six (42.8%) patients died, most of them within weeks of initial admission. All surviving patients underwent prolonged antimicrobial therapy until the resolution of MRI abnormalities. All solid organ transplant recipients recovered. Conclusions Nocardia CNS infection was a rare condition, even among a large, immunosuppressed patient population. CNS imaging surveillance is paramount for immunosuppressed patients with nocardiosis, as CNS involvement influences the choice and duration of therapy. Nocardia antibiotic susceptibility varied widely between strains and the empiric therapy should consist of multiple classes of antimicrobials with CNS penetration. Mortality was high, but all solid organ transplant recipients recovered.

There is lack of consensus on non-tuberculous mycobacteria pulmonary disease (NTM-PD) treatment regimen and duration in patient listed for lung transplantation (LTx). We conducted a systematic review on treatment regimen and duration pre- and directly post-LTx, for patients with known NTM-PD pre-LTx. Additionally, we searched for risk factors for NTM disease development post-LTx and for mortality.

Literature was reviewed on PubMed, Embase and the Cochrane Library, for articles published from inception to January 2022. Individual patient data were sought.

Sixteen studies were included reporting 92 patients. Most frequent used agents were aminoglycosides and macrolides for Mycobacterium abscessus (M. abscessus) and macrolides and tuberculostatic agents for Mycobacterium avium complex (M. avium complex). The median treatment duration pre-LTx was 10 months (IQR 6-17) and 2 months (IQR 2-8) directly post-LTx. Longer treatment duration pre-LTx was observed in children and in patients with M. abscessus. 46% of the patients with NTM-PD pre-LTx developed NTM disease post-LTx, related mortality rate was 10%. Longer treatment duration pre-LTx (p < 0.001) and sputum non-conversion pre-LTx (p = 0.003) were significantly associated with development of NTM-disease post-LTx. Longer treatment duration pre-LTx (p = 0.004), younger age (p < 0.001) and sputum non-conversion (p = 0.044) were risk factors for NTM related death.

The median treatment duration pre-LTx was 10 months (IQR 6-17) and 2 months (IQR 2-8) directly post-LTx. Patients with longer treatment duration for NTM-PD pre-LTx and with sputum non-conversion are at risk for NTM disease post-LTx and for NTM-related death. Children were particularly at risk for NTM related death.

Invasive infection remains a dangerous complication of heart transplantation (HT). No objectively defined set of clinical risk factors has been established to reliably predict infection in HT. The aim of this study was to develop a clinical prediction model for use at 1 mo post-HT to predict serious infection by 1 y.

A retrospective cohort study of HT recipients (2000-2018) was performed. The composite endpoint included cytomegalovirus (CMV), herpes simplex or varicella zoster virus infection, blood stream infection, invasive fungal, or nocardial infection occurring 1 mo to 1 y post-HT. A least absolute shrinkage and selection operator regression model was constructed using 10 candidate variables. A concordance statistic, calibration curve, and mean calibration error were calculated. A scoring system was derived for ease of clinical application.

Three hundred seventy-five patients were analyzed; 93 patients experienced an outcome event. All variables remained in the final model: aged 55 y or above, history of diabetes, need for renal replacement therapy in first month, CMV risk derived from donor and recipient serology, use of induction and/or early lymphodepleting therapy in the first month, use of trimethoprim-sulfamethoxazole prophylaxis at 1 mo, lymphocyte count under 0.75 × 103cells/µL at 1 mo, and inpatient status at 1 mo. Good discrimination (C-index 0.80) and calibration (mean absolute calibration error 3.6%) were demonstrated.

This model synthesizes multiple highly relevant clinical parameters, available at 1 mo post-HT, into a unified, objective, and clinically useful prediction tool for occurrence of serious infection by 1 y post-HT.

Nocardia are Gram-positive, acid-fast, filamentous bacteria that cause opportunistic infections in susceptible populations. We describe a case of post-transplant infection of pulmonary nocardiosis caused by the rare strain Nocardia cyriacigeorgica and the challenges faced in reaching a definitive diagnosis. This case report emphasizes on keeping nocardiosis as a differential diagnosis in transplant recipients, as this disease is largely underdiagnosed and underreported.

Nocardiosis is a rare opportunistic infection seen in kidney transplant patients and is caused by aerobic actinomycete. Disease manifestations can vary from a localized infection to multisystem organ failure. In this retrospective case series, we present 16 cases of Nocardiosis. The median age of the patients was 44 years. The median time from transplant to nocardiosis was 21 months. Acute rejection episodes and CMV infection within 6 months of nocardiosis were found in 12.5% and 25%, respectively. The most common organ involvement was the lungs (75%), followed by the brain (12.5%). Only one patient showed cutaneous involvement (6.25%). Mean creatinine at presentation was 0.7 mg/dL (mean eGFR: 92 ± 27 mL/min/1.73 m2). Trimethoprim/sulfamethoxazole resistance was found in 25% of patients. Five patients (31.25%) succumbed to the infection. Nocardiosis has a very low incidence but a high rate of mortality.

Specific pretransplant infections have been associated with poor posttransplant outcomes. However, the impact of pretransplant Nocardia isolation has not been studied.

We performed a retrospective study from three centers in Arizona, Florida, and Minnesota of patients with Nocardia infection or colonization who subsequently underwent solid organ or hematopoietic stem cell transplantation from November 2011 through April 2022. Outcomes included posttransplant Nocardia infection and mortality.

Nine patients with pretransplant Nocardia were included. Two patients were deemed colonized with Nocardia, and the remaining seven had nocardiosis. These patients underwent bilateral lung (N = 5), heart (N = 1), heart-kidney (N = 1), liver-kidney (N = 1), and allogeneic stem cell transplantation (N = 1) at a median of 283 (interquartile range [IQR] 152-283) days after Nocardia isolation. Two (22.2%) patients had disseminated infection, and two were receiving active Nocardia treatment at the time of transplantation. One Nocardia isolate was resistant to trimethoprim-sulfamethoxazole (TMP-SMX) and all patients received TMP-SMX prophylaxis posttransplant, often for extended durations. No patients developed posttransplant nocardiosis during a median follow-up of 1.96 (IQR 0.90-6.33) years. Two patients died during follow-up, both without evidence of nocardiosis.

This study did not identify any episodes of posttransplant nocardiosis among nine patients with pretransplant Nocardia isolation. As patients with the most severe infections may have been denied transplantation, further studies with larger sample sizes are needed to better analyze any impact of pretransplant Nocardia on posttransplant outcomes. However, among patients who receive posttransplant TMP-SMX prophylaxis, these data suggest pretransplant Nocardia isolation may not impart a heightened risk of posttransplant nocardiosis.

Nocardia is an opportunistic pathogen that primarily affects immunocompromised individuals, including solid organ transplant (SOT) recipients. Up to 2.65% of SOT recipients develop nocardiosis; however, few studies have examined risk factors and prophylaxis for nocardiosis.

We performed a multicenter, matched nested case-control study of adult SOT recipients with culture-confirmed nocardiosis from 2000 through 2020. Controls were matched up to 2:1 by sex, first transplanted organ, year of transplant, transplant center, and adequate post-transplant follow-up. Multivariable conditional logistic regression was performed to analyze associations with nocardiosis. Cox proportional hazards regression compared 12-month mortality between infection and uninfected patients.

One hundred and twenty-three SOT recipients were matched to 245 uninfected controls. Elevated calcineurin inhibitor level, acute rejection, cytomegalovirus infection, lymphopenia, higher prednisone dose, and older age were significantly associated with nocardiosis while trimethoprim-sulfamethoxazole prophylaxis was protective (odds ratio [OR] .34; 95% confidence interval [CI] .13-.84). The effect of prophylaxis was similar, though not always statistically significant, in sensitivity analyses that only included prophylaxis dosed more than twice-per-week (OR .30; 95% CI .11-.80) or restricted to years 2015-2020 (OR .33, 95% CI .09-1.21). Nocardiosis was associated with increased 12-month mortality (hazard ratio 5.47; 95% confidence interval 2.42-12.35).

Multiple measures of immunosuppression and lack of trimethoprim-sulfamethoxazole prophylaxis were associated with nocardiosis in SOT recipients. Effectiveness of prophylaxis may be related to trimethoprim-sulfamethoxazole dose or frequency. Trimethoprim-sulfamethoxazole should be preferentially utilized over alternative agents in SOT recipients with augmented immunosuppression or signs of heightened immunocompromise.

Nocardiosis is a rare bacterial infection caused by Nocardia spp. However, an increasing incidence has been described whereby data about epidemiology and prognosis are essential.

A retrospective descriptive study was conducted among patients with positive Nocardia spp. culture, from January 2019 to January 2023, at a Terciary Hospital in Portugal.

Nocardiosis was considered in 18 cases with a median age of 63.8-years-old. At least one immunosuppressive cause was identified in 70% of patients. Five patients had Disseminated Nocardiosis (DN). The lung was the most common site of clinical disease (77.8%) and Nocardia was most commonly identified in respiratory tract samples. The most frequently isolated species were Nocardia nova/africana (n = 7) followed by Nocardia cyriacigeorgica (n = 3) and Nocardia pseudobrasiliensis (n = 3). The majority of the patients (94.4%) received antibiotic therapy, of whom as many as 55.6% were treated with monotherapy. The most frequently prescribed antibiotic was trimethoprim-sulfamethoxazole. Selected antimicrobial agents were generally effective, with linezolid and cotrimoxazole (100% Susceptibility [S]) and amikacin (94% S) having the most activity against Nocardia species. The median (IQR) duration of treatment was 24.2 (1‒51.4) weeks for DN; The overall one-year case fatality was 33.3% (n = 6) and was higher in the DN (66.7%). No recurrence was observed.

Nocardiosis is an emerging infectious disease with a poor prognosis, particularly in DN. This review offers essential epidemiological insights and underscores the importance of gaining a better understanding of the microbiology of nocardiosis. Such knowledge can lead to the optimization of antimicrobial therapy and, when necessary, guide appropriate surgical interventions to prevent unfavorable outcomes.

Renal transplantation is the treatment of choice in patients with end-stage renal disease. However, allograft recipients are at a higher risk of infection due to immunosuppressive therapies. This study aimed to analyze the utility of fine needle aspiration cytology (FNAC) lung in the etiological diagnosis of pulmonary infections in renal allograft recipients with respiratory failure.

This is a retrospective study done in post-renal transplant patients presenting with pulmonary infections and respiratory failure in the past 7 years, in whom image-guided lung FNAC was done for diagnosis.

A total of 35 renal allograft recipients presenting with respiratory failure and having focal or diffuse pulmonary opacities (lesions) on radiological imaging were subjected to lung FNAC. The mean age of the patients was 41.1 ± 11.8 years (range 19-72), with the majority being males (n = 28, 80%); six (17.1%) of them were on invasive ventilation. The diagnostic yield of FNAC in our cohort was 77.1% (27 out of 35). Microorganisms were isolated in 21 cases (60%), with Nocardia being the most common (nine cases, 25.7%), Mycobacterial tuberculosis identified in six patients (17.1%), Aspergillus in three (8.6%), and one (2.9%) each had atypical Mycobacterium, zygomycetes, and Cryptococcus. FNAC suggested viral cytopathic effect in five patients, and cytomegalovirus (CMV) quantitative polymerase chain reaction test was found positive in four of these. One case was diagnosed as adenocarcinoma lung.

Lung FNAC is a useful for establishing the etiological diagnosis of pulmonary lesions in renal transplant patients with respiratory failure.

Nocardia caishijiensis is a rare soil actinomycete first described in Anhui province, China, in 2003. There has been only one reported instance of human infection caused by this species in the current literature.

We present a case of pulmonary nocardiosis caused by Nocardia caishijiensis in a fifty-two-year-old man with human immunodeficiency virus infection and concomitant use of high-dose dexamethasone for cervical myelopathy, treated successfully with amikacin and thrimetroprim-sulfametoxazole, antibiotic resistance pattern was obtained, although interpretation may be limited.

To our knowledge, this is the first reported case of Nocardia caishijiensis infection in humans in North America and the second one in the literature, this pathogen should be recognized as a potentially rising etiology of nocardiosis, especially in solid organ transplant recipients. This has a rising importance as the survival for solid organ recipients continue to rise with advance in transplant medicine leading to increased life expectancy in this particularly susceptible group.

Nocardia is an environmental pathogen with a predilection for causing opportunistic infections in immunocompromised patients, including solid organ transplant (SOT) recipients. Although risk factors have been identified for developing nocardiosis in this population, little is known regarding clinical factors resulting in poor outcomes. We evaluated a cohort of SOT recipients with nocardiosis for associations with 12-month mortality.

We performed a multicenter retrospective cohort study of adult SOT recipients diagnosed with culture-confirmed nocardiosis from 2000 to 2020. Patients were followed for 12 months after diagnosis, unless abbreviated by mortality. Multivariable Cox regression was performed to analyze associations with 12-month mortality. A subgroup analysis of patients with disseminated nocardiosis was performed to analyze treatment variables.

A total of 125 SOT recipients met inclusion criteria; 12-month mortality was 16.8%. Liver transplantation (hazard ratio [HR] 3.52; 95% confidence interval [CI] 1.27-9.76) and time from symptom onset to presentation (HR 0.92/d; 95% CI 0.86-0.99) were independently associated with 12-month mortality, whereas disseminated infection was not (HR 1.23; 95% CI 0.49-3.13). No treatment-specific factors were significantly associated with mortality in 33 patients with disseminated nocardiosis, although survivors had a higher rate of linezolid use.

This study identified 2 independent associations with 12-month mortality, representing demographics and infection severity. Disseminated infection was not independently associated with poor outcomes, and specific sites of infection may be more important than dissemination itself. No treatment-specific factors were associated with mortality, though this analysis was likely underpowered. Further study of treatment strategies based on specific Nocardia syndromes is warranted.

Pulmonary nocardiosis is a rare pulmonary infection with high morbidity and mortality. Limited real-world data on pulmonary nocardiosis patients are available from developing countries like Pakistan.

This retrospective observational study was conducted at the Aga Khan University Hospital, Karachi, Pakistan, from August 2003 to June 2020. Demographics, immune status, underlying diseases, laboratory data, treatment, and outcomes of all nocardiosis patients were recorded in predesigned proforma.

Sixty-six patients with smear/culture-proven pulmonary nocardiosis were identified. Most patients (83.3%) were treated with trimethoprim-sulfamethoxazole alone or in combination with other medicines. The overall mortality rate in our study was 33.3% (n = 22/66). Factors significantly associated with mortality were respiratory failure (p < 0.001), raised procalcitonin levels (p = 0.01), concomitant fungal infections (p = 0.01), concomitant TB (p = 0.03), and patients on combination therapy (p < 0.001). Respiratory failure (odds ratio [OR] 46.94 [95% confidence intervals [CI]: 5.01-439.03] p < 0.001), concomitant fungal infection (OR 17.09 [95% CI: 1.47-197.88] p- = 0.02) and patients on combination therapy (OR 6.90 [95% CI: 1.23-38.61] p = 0.02) were also identified as independent risk factors for mortality on multivariate analysis.

This study provides essential information on the clinical characteristics and risk factors, outcomes, and factors associated with mortality for pulmonary nocardial infections.

Nocardiosis occurs in up to 1.7% of hematopoietic stem cell transplantation (HSCT) recipients. Risk factors for its development and subsequent outcomes have been incompletely studied. The present study evaluated risk factors for nocardiosis in HSCT recipients and an association with 12-month mortality following Nocardia infection. We performed a nested case-control study of HSCT recipients at 3 transplantation centers between 2011 and 2021. Allogeneic HSCT recipients were matched 1:4 to controls based on age, sex, date of transplantation, and transplantation site. Because of theorized differences in the risk for nocardiosis between allogeneic HSCT recipients and autologous HSCT recipients and a low number of infected autologous HSCT recipients, only allogeneic HSCT recipients were matched to controls. Associations with nocardiosis in the allogeneic group were assessed by multivariable conditional logistic regression. Outcomes of all HSCT recipients with nocardiosis included 12-month mortality and post-treatment recurrence. Twenty-seven HSCT recipients were diagnosed with nocardiosis, including 20 allogeneic HSCT recipients and 7 autologous HSCT recipients. Twenty (74.1%) had localized pulmonary infection, 4 (14.8%) had disseminated infection, and 3 (11.1%) had localized skin infection. The allogeneic recipients were diagnosed at a median of 12.2 months after transplantation, compared with 41 months for the autologous recipients. All autologous HSCT recipients had alternative reasons for ongoing immunosuppression at diagnosis, most frequently therapy for relapsed hematologic disease. No infected patients were receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. In multivariable analysis of 20 allogeneic patients and 80 matched controls, graft-versus-host disease (GVHD) requiring current immunosuppression and lack of prophylaxis were associated with nocardiosis. Nocardiosis was significantly associated with subsequent mortality, with a 12-month mortality rate of 29.6%; however, no patients who completed treatment experienced Nocardia recurrence. OUR DATA INDICATE THAT: intensified immunosuppression following allogeneic HSCT, such as treatment for GVHD, is associated with the development of nocardiosis. Nocardiosis occurs more distantly from transplantation in autologous recipients, possibly driven by therapy for relapsed hematologic disease. No patients receiving TMP-SMX prophylaxis developed nocardiosis. Nocardia infection is associated with high mortality, and further strategies for prevention and treatment are needed.