Rhodococcus infection: a 10-year retrospective analysis of clinical experience and antimicrobial susceptibility profile.

Rhodococcus equi is an opportunistic pathogen known to cause pulmonary and extrapulmonary disease among immunocompromised patients. Treatment is frequently challenging due to intrinsic resistance to multiple antibiotic classes. While non-equi Rhodococcus spp. are prevalent, their clinical significance is poorly defined. There is also limited data on antibiotic susceptibility testing (AST) of Rhodococcus infection in humans. We conducted a single-center, retrospective cohort study evaluating clinical characteristics, microbiologic profile, and AST of Rhodococcus infections between June 2012 and 2022 at our tertiary academic medical center. Identification of Rhodococcus spp. was performed by Sanger 16S rRNA gene sequencing and/or matrix-assisted laser desorption ionization-time of flight mass spectrometry, and AST was performed by agar dilution. Three hundred twenty-two isolates of Rhodococcus spp. were identified from blood (50%), pulmonary (26%), and bone/joint (12%) sources. R. equi/hoagii, R. corynebacterioides, and R. erythropolis were the most frequently isolated species, with 19% of isolates identified only to genus level. One hundred ninety-nine isolates evaluated for AST demonstrated high-level resistance to amoxicillin/clavulanate, cephalosporins, and aminoglycosides. More than 95% susceptibility to imipenem, vancomycin, linezolid, rifampin, and clarithromycin was observed. Non-equi species showed a significantly more favorable AST profile relative to R. equi. Clinically significant Rhodococcus infection was rare with 10 cases diagnosed (majority due to R. equi) and managed. The majority of patients received 2- or 3-drug combination therapy for 2-6 months, with favorable clinical response. Significant differences in AST were observed between R. equi and non-equi species. Despite high antimicrobial resistance to several antibiotic classes, imipenem and vancomycin remain appropriate empiric treatment options for R. equi. Future research evaluating mechanisms underlying antimicrobial resistance is warranted.

Successful treatment of Rhodococcus lung abscess and empyema thoracis in a heart transplant recipient.

Rhodococcosis is an uncommon cause of pulmonary infection in thoracic organ transplant recipients. We describe a heart transplant recipient diagnosed with Rhodococcus equi left upper lung abscess with empyema thoracis complicated by bacteremia. The patient was successfully treated with appropriate antibiotics, adequate surgical resection, and optimization of immunosuppressants.

International Spread of Multidrug-Resistant Rhodococcus equi.

A multidrug-resistant clone of the animal and human pathogen Rhodococcus equi, MDR-RE 2287, has been circulating among equine farms in the United States since the 2000s. We report the detection of MDR-RE 2287 outside the United States. Our finding highlights the risk for MDR-RE spreading internationally with horse movements.

A rare case of male Fournier's gangrene with mixed Actinomyces turicensis infection.

BACKGROUND: Fournier's gangrene (FG), a urological emergency with high mortality, is an infectious necrotizing fasciitis of the perineal and genital regions. The majority of FG is caused by polymicrobial organisms involving mixed aerobes and anaerobes but rarely reveals Actinomyces species. CASE PRESENTATION: We report a healthy 67-year-old Asian male who presented with rapidly progressive painful swelling of the scrotum. Clinically diagnosed with FG, the patient underwent an emergency radical debridement, followed by broad-spectrum antibiotics and negative pressure wound therapy. The identification of the causative microorganisms showed Actinomyces turicensis and the antibiotic treatment was adjusted accordingly. After wound bed preparation, we took split-thickness skin grafts to cover the scrotal wound. Active management to minimize faecal contamination was applied throughout the whole course of treatment and repair. The patient was satisfied with the outcome. This was an extremely rare case of A. turicensis as the main causative pathogen of FG. CONCLUSIONS: FG due to Actinomyces species is rarely reported, but we should still consider this pathogenic microorganism that has long been neglected.

Spread of Multidrug-Resistant Rhodococcus equi, United States.

Multidrug resistance has been detected in the animal and zoonotic human pathogen Rhodococcus equi after mass macrolide/rifampin antibioprophylaxis in endemically affected equine farms in the United States. Multidrug-resistant (MDR) R. equi emerged upon acquisition of pRERm46, a conjugative plasmid conferring resistance to macrolides, lincosamides, streptogramins, and, as we describe, tetracycline. Phylogenomic analyses indicate that the increasing prevalence of MDR R. equi since it was first documented in 2002 is caused by a clone, R. equi 2287, attributable to coselection of pRErm46 with a chromosomal rpoBS531F mutation driven by macrolide/rifampin therapy. pRErm46 spillover to other R. equi genotypes has given rise to a novel MDR clone, G2016, associated with a distinct rpoBS531Y mutation. Our findings illustrate that overuse of antimicrobial prophylaxis in animals can generate MDR pathogens with zoonotic potential. MDR R. equi and pRErm46-mediated resistance are currently disseminating in the United States and are likely to spread internationally through horse movements.

Septic hip abscess due to Fusobacterium nucleatum and Actinomyces turicensis in an immunocompetent SARS-CoV-2 positive patient.

A 42-year-old man was referred to the Department of Orthopedic Surgery with pain over his right greater trochanter and signs of systemic infection. CT showed an enhanced mass in his gluteus maximus as well as gas in the biceps femoris over the underlying hip joint. Tissue biopsy yielded Fusobacterium nucleatum and Actinomyces turicensis. The patient was successfully treated for 6 weeks with amoxicillin/clavulanic acid 875mg/125mg and metronidazole 500mg.

A case report of the differential diagnosis of Cellulosimicrobium cellulans-infected endocarditis combined with intracranial infection by conventional blood culture and second-generation sequencing.

BACKGROUND: Cellulosimicrobium cellulans is a gram-positive filamentous bacterium found primarily in soil and sewage that rarely causes human infection, especially in previously healthy adults, but when it does, it often indicates a poor prognosis. CASE PRESENTATION: We report a case of endocarditis and intracranial infection caused by C. cellulans in a 52-year-old woman with normal immune function and no implants in vivo. The patient started with a febrile headache that progressed to impaired consciousness after 20 days, and she finally died after treatment with vancomycin combined with rifampicin. C. cellulans was isolated from her blood cultures for 3 consecutive days after her admission; however, there was only evidence of C. cellulans sequences for two samples in the second-generation sequencing data generated from her peripheral blood, which were ignored by the technicians. No C. cellulans bands were detected in her cerebrospinal fluid by second-generation sequencing. CONCLUSIONS: Second-generation sequencing seems to have limitations for certain specific strains of bacteria.

Half of 'Micrococcus spp.' cases identified by conventional methods are revealed as other life-threatening bacteria with different drug susceptibility patterns by 16S ribosomal RNA gene sequencing.

Bacterial infection during chemotherapy is a fatal complication, therefore precise identification of the pathogenic microorganism is required for treatment. We report that 2 of 4 pediatric patients with malignancy who were diagnosed with Micrococcus spp. infection by conventional methods were finally revealed to have Kytococcus schroeteri and Kocuria marina infection by 16S ribosomal RNA gene sequence analysis (16S rRNA analysis). Although K. schroeteri is morphologically similar to Micrococcus spp., its drug susceptibility profile is quite different from that of Micrococcus spp. K. schroeteri is resistant to penicillin and cephalosporin, which are effective for Micrococcus spp. In fact, penicillin-resistant lethal pneumonia caused by K. schroeteri has been reported in compromised hosts. Based on our results, Micrococcus spp. determined by conventional methods could contain other life-threatening bacteria with different drug susceptibility patterns from Micrococcus spp. To develop an effective empirical treatment for immunocompromised hosts, accumulation of pathogen data by 16S rRNA analysis is required.

Clinical and Biological Features of Cutibacterium (Formerly Propionibacterium) avidum, an Underrecognized Microorganism.

The recent description of the genus Cutibacterium has altered the taxonomy of Propionibacterium species. These organisms still belong to the genera of the skin coryneform group, and the most-studied species remains Cutibacterium acnes. Cutibacterium avidum is also a known skin commensal. This underrecognized microorganism can, however, act as a pathogen after bacterial seeding and can be considered opportunistic, causing either superficial or deep/invasive infections. It can cause numerous infections, including but not limited to breast infections, skin abscesses, infective endocarditis, and device-related infections. The ecological niche of C. avidum is clearly different from that of other members of the genus: it is found in the axillary region or at wet sites rather than in dry, exposed areas, and the number of microorganisms increases during puberty. Historically, it has been used for its ability to modulate the immune response and for its antitumor properties. Conventional microbial culture methods and identification processes allow for its accurate identification and characterization. Thanks to the modern omics tools used for phylogenomic approaches, understanding C. avidum pathogenesis (including host-bacterium interactions and virulence factor characterization) is becoming easier, allowing for more thorough molecular characterization. These analyses have revealed that C. avidum causes diverse diseases mediated by multiple virulence factors. The recent genome approach has revealed specific genomic regions within this species that are involved in adherence and biofilm formation as well as fitness, survival, and defense functions. Numerous regions show the presence of phages and horizontal gene transfer. C. avidum remains highly sensitive to a broad spectrum of antibiotics, such as ß-lactams, fluoroquinolones, macrolides, and rifampin, although erythromycin and clindamycin resistance has been described. A long-term treatment regimen with a combination of antibiotics is required to successfully eliminate the remaining adherent bacteria, particularly in the case of deep infections after debridement surgery.

Bacteremia and sepsis by Arcanobacterium haemolyticum in a young immunocompetent patient.

We report the case of a twenty-year-old immunocompetent male patient presenting to the emergency room with pharyngitis and fever. Blood cultures were drawn and Arcanobacterium haemolyticum (rough biotype) was recovered. The presence of the arcanolysin gene was investigated at the molecular level and the upstream region was amplified and sequenced in order to correlate it with the smooth or rough biotype. Although the isolate was susceptible to penicillin, vancomycin and gentamicin, empirical treatments first with amoxicillin/clavulanic acid (1g/12h) and then with ceftriaxone (1g/12h) failed and the infection evolved to sepsis. Finally, treatment with vancomycin (1g/12h) plus piperacillin/tazobactam (4.5g/8h) was effective. Lemierre's syndrome was ruled out. To the best of our knowledge, this is the first case of bacteremia by A. haemolyticum reported in Argentina.

Effect of Macrolide and Rifampin Resistance on Fitness of Rhodococcus equi during Intramacrophage Replication and In Vivo.

The soil-dwelling, saprophytic actinomycete Rhodococcus equi is a facultative intracellular pathogen of macrophages and causes severe bronchopneumonia when inhaled by susceptible foals. Standard treatment for R. equi disease is dual-antimicrobial therapy with a macrolide and rifampin. Thoracic ultrasonography and early treatment with antimicrobials prior to the development of clinical signs are used as means of controlling endemic R. equi infection on many farms. Concurrently with the increased use of macrolides and rifampin for chemoprophylaxis and the treatment of subclinically affected foals, a significant increase in the incidence of macrolide- and rifampin-resistant R. equi isolates has been documented. Previously, our laboratory demonstrated decreased fitness of R. equi strains that were resistant to macrolides, rifampin, or both, resulting in impaired in vitro growth in iron-restricted media and in soil. The objective of this study was to examine the effect of macrolide and/or rifampin resistance on intracellular replication of R. equi in equine pulmonary macrophages and in an in vivo mouse infection model in the presence and absence of antibiotics. In equine macrophages, the macrolide-resistant strain did not increase in bacterial numbers over time and the dual macrolide- and rifampin-resistant strain exhibited decreased proliferation compared to the susceptible isolate. In the mouse model, in the absence of antibiotics, the susceptible R. equi isolate outcompeted the macrolide- or rifampin-resistant strains.

Emergence of Resistance to Macrolides and Rifampin in Clinical Isolates of Rhodococcus equi from Foals in Central Kentucky, 1995 to 2017.

The objective of this study was to determine the prevalence of Rhodococcus equi strains resistant to macrolides and rifampin over time in clinical samples from foals submitted to diagnostic laboratories in central Kentucky. We performed a retrospective observational study of all clinical samples from foals that were submitted to veterinary diagnostic laboratories in Kentucky between January 1995 and December 2017. Samples were included if the R. equi bacterium was cultured and tested for in vitro susceptibility to erythromycin or rifampin. In vitro susceptibility testing to erythromycin was available for 2,169 isolates of R. equi, while susceptibility testing to both erythromycin and rifampin was available for 1,681 isolates. Rifampin resistance was first detected in 2000, and erythromycin resistance was first detected in 2004. Between 1995 and 2006, the proportion of resistant isolates of R. equi was 0.7% for erythromycin and 2.3% for rifampin. There was a significant (P < 0.001) increase in the proportion of resistant R. equi between 2007 and 2017, with 13.6% of isolates being resistant to erythromycin and 16.1% being resistant to rifampin. Between 2007 and 2017, isolates of R. equi resistant to erythromycin or rifampin were significantly less likely to be isolated from feces than from the respiratory tract, other soft tissues, or musculoskeletal infections. The considerable increase in the prevalence of isolates of R. equi resistant to macrolides and rifampin since 2007 is of concern for both human and animal health.

Brevibacterium paucivorans bacteremia: case report and review of the literature.

BACKGROUND: Brevibacteria are obligate aerobic gram-positive rods that are associated with milk products and are also found on human skin. Brevibacterium has been reported as a rare cause of catheter related blood steam infection mainly in immunocompromised hosts such as malignancies or AIDS patients. CASE PRESENTATION: A 94-year old woman, which had a past history of diabetes mellitus and chronic heart failure, presented with high fever associated with decreased oral intake and appetite loss and was admitted to our institute. A physical examination at the time of presentation was unremarkable. On day 2, both blood cultures collected on admission became positive with coryneform organism within 24 h without Staphylococci and Brevibacterium species were identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Subsequently, genetic investigation by 16S ribosomal RNA analysis was performed in order to identify the organism. Finally, the result identified this pathogen as Brevibacterium paucivorans with 99.5% homology on the Ez taxon database. The patient was started empirically on meropenem and teicoplanin for broad-spectrum antibiotic coverage. The patient's fever finally abated and labs were also improved. On day 14, the antibiotic therapy was discontinued. The site of infections was unknown. We hereby report a case of Brevibacterium paicivorans bacteremia in an immunocompetent patient and review cases of Brevibacterium specises bacteremia previously reported. This is the first case of B. paucivorans bacteremia as far as we could search. CONCLUSION: Physicians and microbiologists should be aware that Brevibacteria are uncommon but important agents which could cause opportunistic infections in immunocompetent.

Infections due to Cellulosimicrobium species: case report and literature review.

BACKGROUND: Cellulosimicrobium species, formely known as Oerskovia species, are gram-positive bacilli belonging to the order Actinomycetales. They rarely cause human infections. The genus comprises two pathogenic species in humans: C. cellulans and C. funkei. Based on a case report, we provide a review of the literature of infections caused by Cellulosimicrobium/Oerskovia, in order to improve our knowledge of this unusual infection. CASE PRESENTATION: An 82-year-old woman with aortic prosthetic valve presented to the hospital with fever and heart failure. Further work up revealed the diagnosis of C. cellulans infective endocarditis (IE). The strain was identified by MALDI-TOF MS, API Coryne and 16S rRNA sequencing. The patient was deemed not to be an operative candidate and died despite the antibiotic therapy 35 days after admission. CONCLUSIONS: Reviewing cases of Cellulosimicrobium species infections and communicating the successful and unsuccessful clinical experiences can assist future healthcare providers. Our case and those previously reported indicate that Cellulosimicrobium species usually infect immunocompromised patients or foreign body carriers. The most frequent pattern of infection is central venous catheter related bacteremia. The optimal treatment should include foreign body removal and valve surgery should be considered in case of IE.

Ophthalmologic findings associated with Rhodococcus equi bronchopneumonia in foals.

OBJECTIVE: To describe ocular findings associated with Rhodococcus equi bronchopneumonia in foals, and to determine whether severity of the ocular lesions is related with outcome. ANIMALS STUDIED: Foals diagnosed with R equi infection at the VTH-UAB from January 2002 to December 2017. PROCEDURE: Rhodococcus equi infection was diagnosed by means of clinical signs, radiographic/ultrasonographic findings, and/or positive culture. In all the foals, a complete ophthalmic examination by a boarded ophthalmologist was performed and ocular signs were recorded and graded (0-4). RESULTS: Thirty-nine foals were included in the study, from which 12 showed signs of bilateral anterior uveitis (30.8%). Among these, three foals were classified as mildly uveitis-affected (MUA:7.7%) and nine as severely uveitis-affected (SUA:23.1%). Five SUA foals showed green aqueous flare (5/9;55.5%). Despite the systemic treatment, 9/39 sick foals died (23.1%), the fatality rate being different between groups: SUA (4/9;44.4%), MUA (0/3; 0%) and nonuveitis-affected foals (5/27;18.5%). Among SUA foals, only one with green aqueous flare died (1/5;20%). CONCLUSION: Bilateral anterior uveitis is highly prevalent in foals with R equi pneumonia (30.8%). The severity of anterior uveitis might be considered a nonsurvival prognostic factor and, until proven otherwise, green aqueous flare could be taken as a strongly suggestive ocular sign of the disease. Findings of this study remark the clinical relevance of performing a complete ophthalmic examination in sick foals, in order to help in the diagnosis and prognosis of uveal diseases, as well as to guaranteeing visual soundness.

The first reported case of pelvic inflammatory disease caused by Actinobaculum massiliense.

We report the first case of pelvic inflammatory disease (PID) caused by Actinobaculum massiliense. A 53-year-old woman attended the emergency department with symptoms compatible with a PID episode, finally resolved by intramuscular antibiotic treatment. Actinobaculum sp. was isolated by culture, and A. massiliense was confirmed by matrix assisted laser desorption time-of-flight mass spectrometry and 16S rRNA gene sequencing. Only a few cases of A. massiliense infections have been reported, and the pathogenesis of infections by these bacteria is poorly understood. The introduction of new diagnostic methods into hospital routines will improve the detection of new and little-studied pathogens.

Antimicrobial resistance and presence of virulence factor genes in Trueperella pyogenes isolated from pig lungs with pneumonia.

Trueperella pyogenes (T. pyogenes) is a worldwide known pathogen of domestic ruminants and pigs causing a wide variety of infections. The objective of this study was to report the presence of major virulence genes in T. pyogenes isolated from pigs with respiratory clinical signs and determine their resistance to antibiotics at the same time. A total of 27 T. pyogenes strains were obtained from Jilin Province, and the nanH, nanP, cbpA, fimC, and fimE virulence genes were detected in 7 (25.9%), 14 (51.9%), 18 (66.7%), 8 (29.6%), and 16 (59.3%) isolates, respectively. All isolates were observed to harbor plo and fimA genes. However, 27 T. pyogenes strains tested negative for fimG gene. Antibiotic susceptibility tests revealed that the isolated strains had extensive drug resistance, all isolates were sensitive to fluoroquinolones and penicillins antibiotics, and high levels of resistance were found to gentamicin (77.8%), amikacin (74.1%), erythromycin (85.2%), and azithromycin (85.2%). These results highlights the need for prudent use of specific antimicrobial agents in veterinary clinical treatment.

Elfamycins: inhibitors of elongation factor-Tu.

Elfamycins are a relatively understudied group of antibiotics that target the essential process of translation through impairment of EF-Tu function. For the most part, the utility of these compounds has been as laboratory tools for the study of EF-Tu and the ribosome, as their poor pharmacokinetic profile and solubility has prevented implementation as therapeutic agents. However, due to the slowing of the antibiotic pipeline and the rapid emergence of resistance to approved antibiotics, this group is being reconsidered. Some researchers are using screens for novel naturally produced variants, while others are making directed, systematic chemical improvements on publically disclosed compounds. As an example of the latter approach, a GE2270 A derivative, LFF571, has completed phase 2 clinical trials, thus demonstrating the potential for elfamycins to become more prominent antibiotics in the future.

First case of a bloodstream infection caused by the genus Brachybacterium.

An 83-year-old previously self-sufficient man was referred to our hospital for a fever, severe tenderness over the lumbar spine, and elevated C-reactive protein levels. Computed tomography revealed fluid collection in the intervertebral space of L3/4. Gram-positive, short rod-shaped bacteria were isolated from two sets of blood cultures. A 16S rRNA sequence analysis of an isolate showed a similarity of 98.1% to the nearest type strain Brachybacterium squillarum JCM 16464T. Biochemical characteristics of the presently isolated strain differed from those of the most closely related species of the genus Brachybacterium. The patient was successfully discharged on day 73 of admission with antimicrobial therapies and showed no recurrence during outpatient visits. Brachybacterium spp. have mainly been isolated from the environment, and human Brachybacterium infections have rarely been documented to date. To our knowledge, this is the first clinical isolation of Brachybacterium sp. as a causative pathogen of bloodstream infection.

Minimum inhibitory concentrations of frequently used antibiotics against Escherichia coli and Trueperella pyogenes isolated from uteri of postpartum dairy cows.

The objective of this study was to determine minimum inhibitory concentrations (MIC) of frequently used antimicrobials for Escherichia coli and Trueperella pyogenes isolated from postpartum bovine uteri of cows with acute puerperal metritis (APM, n = 67), cows suspected to have APM (n = 37), and healthy cows (n = 37) and to evaluate possible differences in MIC according to clinical signs. Cows with APM had reddish-brown, fetid vaginal discharge and rectal temperature (RT) ≥39.5°C within 21 d in milk; cows suspected to have APM had either reddish-brown, fetid vaginal discharge or RT ≥39.5°C within 21 d in milk; and healthy cows had neither fetid discharge nor RT ≥39.5°C. Samples were collected from cows on commercial dairy herds (n = 7) using the cytobrush technique. A total of 37 T. pyogenes isolates and 85 E. coli isolates were tested. Ceftiofur, a third-generation cephalosporin that is often used to treat APM, was the focus of analysis. Trueperella pyogenes and E. coli were isolated more often from samples of cows with APM (46 and 90%, respectively) compared with samples from healthy cows (19 and 54%, respectively). Regarding cows suspected to have APM, T. pyogenes and E. coli were numerically more often isolated (30 and 70%, respectively) than in healthy cows (19 and 54%, respectively). Minimum inhibitory concentrations of ceftiofur were low. For T. pyogenes and E. coli, MIC50 (concentration that inhibited growth of 50% of isolates) were 0.25 and 0.5 µg/mL and MIC90 (concentration that inhibited growth of 90% of isolates) were 0.5 and 1 µg/mL, respectively. Although ceftiofur inhibited all T. pyogenes at the highest concentration tested (64 µg/mL), the growth of 5.9% of E. coli was not impaired. Recently, ampicillin has been suggested as an alternative treatment for APM. Although the T. pyogenes isolates exhibited low MIC in general (MIC50 ≤0.015 µg/mL and MIC90 = 0.06 µg/mL) and 81.1% of all T. pyogenes could be inhibited at the lowest ampicillin concentration tested, 11.8% of the E. coli isolates were not impaired at the highest concentration (64 µg/mL) tested in this study. The MIC50 and MIC90 of E. coli were 4 and ≥128 µg/mL, respectively. We detected no difference in the MIC distributions of ceftiofur or ampicillin among isolates from the 3 APM groups. In summary, E. coli with high MIC against ceftiofur as well as against ampicillin were found in this study.