Infection In Immunocompetent Hosts Research Articles

Divergent co-transcriptomes of different host cells infected with Toxoplasma gondii reveal cell type-specific host-parasite interactions

The apicomplexan parasite Toxoplasma gondii infects various cell types in avian and mammalian hosts including humans. Infection of immunocompetent hosts is mostly asymptomatic or benign, but leads to development of largely dormant bradyzoites that persist predominantly within neurons and muscle cells. Here we have analyzed the impact of the host cell type on the co-transcriptomes of host and parasite using high-throughput RNA sequencing. Murine cortical neurons and astrocytes, skeletal muscle cells (SkMCs) and fibroblasts differed by more than 16,200 differentially expressed genes (DEGs) before and after infection with T. gondii. However, only a few hundred of them were regulated by infection and these largely diverged in neurons, SkMCs, astrocytes and fibroblasts indicating host cell type-specific transcriptional responses after infection. The heterogeneous transcriptomes of host cells before and during infection coincided with ~5,400 DEGs in T. gondii residing in different cell types. Finally, we identified gene clusters in both T. gondii and its host, which correlated with the predominant parasite persistence in neurons or SkMCs as compared to astrocytes or fibroblasts. Thus, heterogeneous expression profiles of different host cell types and the parasites’ ability to adapting to them may govern the parasite-host cell interaction during toxoplasmosis.

Impact of the host on Toxoplasma stage differentiation.

The unicellular parasite Toxoplasma gondii infects warm-blooded animals and humans, and it is highly prevalent throughout the world. Infection of immunocompetent hosts is usually asymptomatic or benign but leads to long-term parasite persistence mainly within neural and muscular tissues. The transition from acute primary infection towards chronic toxoplasmosis is accompanied by a developmental switch from fast replicating and metabolically highly active tachyzoites to slow replicating and largely dormant bradyzoites within tissue cysts. Such developmental differentiation is critical for T. gondii in order to complete its life cycle and for pathogenesis. Herein, we summarize accumulating evidence indicating a major impact of the host cell physiology on stage conversion between the tachyzoite and the bradyzoite stage of the parasite. Withdrawal from cell cycle progression, proinflammatory responses, reduced availability of nutrients and extracellular adenosine can indeed induce tachyzoite-to-bradyzoite differentiation and tissue cyst formation. In contrast, high glycolytic activity as indicated by increased lactate secretion can inhibit bradyzoite formation. These examples argue for the intriguing possibility that after dissemination within its host, T. gondii can sense its cellular microenvironment to initiate the developmental program towards the bradyzoite stage in distinct cells. This may also explain the predominant localization of T. gondii in neural and muscular tissues during chronic toxoplasmosis.

IL-33/ST2 pathway drives regulatory T cell dependent suppression of liver damage upon cytomegalovirus infection.

Regulatory T (Treg) cells dampen an exaggerated immune response to viral infections in order to avoid immunopathology. Cytomegaloviruses (CMVs) are herpesviruses usually causing asymptomatic infection in immunocompetent hosts and induce strong cellular immunity which provides protection against CMV disease. It remains unclear how these persistent viruses manage to avoid induction of immunopathology not only during the acute infection but also during life-long persistence and virus reactivation. This may be due to numerous viral immunoevasion strategies used to specifically modulate immune responses but also induction of Treg cells by CMV infection. Here we demonstrate that liver Treg cells are strongly induced in mice infected with murine CMV (MCMV). The depletion of Treg cells results in severe hepatitis and liver damage without alterations in the virus load. Moreover, liver Treg cells show a high expression of ST2, a cellular receptor for tissue alarmin IL-33, which is strongly upregulated in the liver of infected mice. We demonstrated that IL-33 signaling is crucial for Treg cell accumulation after MCMV infection and ST2-deficient mice show a more pronounced liver pathology and higher mortality compared to infected control mice. These results illustrate the importance of IL-33 in the suppressive function of liver Treg cells during CMV infection.

Mycobacterium genavense invading the bone marrow in a HIV‐positive patient

Key Clinical MessageNontuberculous mycobacteria infrequently cause disseminated infections in immunocompetent hosts. However, they are increasingly being recognized in immunocompromised patients. We present the case of a 40‐year‐old HIV‐positive male presenting with lymphadenopathies and pancytopenia in whom disseminated infection, with bone marrow involvement by Mycobacterium genavense (M. genavense) was diagnosed.

Nontuberculous mycobacterial infection of the musculoskeletal system in immunocompetent hosts.

Background:Nontuberculous mycobacteria (NTM) were considered saprophytic organisms for many years but now are recognized as human pathogens. Although humans are routinely exposed to NTM, the rate of clinical infection is low. Such infections usually occur in the elderly and in patients who are immunocompromised. However, there has been an increasing incidence in recent years of infections in immunocompetent hosts. NTM infections in immunocompetent individuals are secondary to direct inoculation either contamination from surgical procedures or penetrating injuries rather than hematogenous dissemination. Clinically and on histopathology, musculoskeletal infections caused by NTM resemble those caused by Mycobacterium tuberculosis but are mostly resistant to routine antituberculosis medicines.Materials and Methods:Six cases of NTM infection in immunocompetent hosts presenting to the department from 2004 to 2015 were included in study. Of which two cases (one patella and one humerus) of infection were following an open wound due to trauma while two cases (one hip and one shoulder) of infection were by inoculation following an intraarticular injection for arthrogram of the joint, one case was infection following arthroscopy of knee joint and one case (calcaneum) was infection following local injection for the treatment of plantar fasciitis. All patients underwent inaging and tissue diagnosis with samples being sent for culture, staining, and histopathology.Results:Clinical suspicion of NTM inoculation led to the correct diagnosis (four cases with culture positive and two cases with histopathological diagnosis). There treatment protocol for extrapulmonary NTM infection was radical surgical debridement and medical management based on drug sensitivity testing in culture positive cases. At a mean follow up of 3 years (range1–9 years) all patients had total remission and excellent results.Conclusions:Whenever a case of chronic granulomatous infection is encountered that does not respond to standard anti-tuberculous treatment, with a history of open trauma, surgical intervention, or injection as shown in this study, a possible NTM infection should be considered and managed appropriately.

Restricted TET2 Expression in Germinal Center Type B Cells Promotes Stringent Epstein-Barr Virus Latency.

Epstein-Barr virus (EBV) latently infects normal B cells and contributes to the development of certain human lymphomas. Newly infected B cells support a highly transforming form (type III) of viral latency; however, long-term EBV infection in immunocompetent hosts is limited to B cells with a more restricted form of latency (type I) in which most viral gene expression is silenced by promoter DNA methylation. How EBV converts latency type is unclear, although it is known that type I latency is associated with a germinal center (GC) B cell phenotype, and type III latency with an activated B cell (ABC) phenotype. In this study, we have examined whether expression of TET2, a cellular enzyme that initiates DNA demethylation by converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), regulates EBV latency type in B cells. We found that TET2 expression is inhibited in normal GC cells and GC type lymphomas. In contrast, TET2 is expressed in normal naive B cells and ABC type lymphomas. We also demonstrate that GC type cell lines have increased 5mC levels and reduced 5hmC levels in comparison to those of ABC type lines. Finally, we show that TET2 promotes the ability of the EBV transcription factor EBNA2 to convert EBV-infected cells from type I to type III latency. These findings demonstrate that TET2 expression is repressed in GC cells independent of EBV infection and suggest that TET2 promotes type III EBV latency in B cells with an ABC or naive phenotype by enhancing EBNA2 activation of methylated EBV promoters.IMPORTANCE EBV establishes several different types of viral latency in B cells. However, cellular factors that determine whether EBV enters the highly transforming type III latency, versus the more restricted type I latency, have not been well characterized. Here we show that TET2, a cellular enzyme that initiates DNA demethylation by converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), regulates EBV latency type in B cells by enhancing the ability of the viral transcription factor EBNA2 to activate methylated viral promoters that are expressed in type III (but not type I) latency. Furthermore, we demonstrate that (independent of EBV) TET2 is turned off in normal and malignant germinal center (GC) B cells but expressed in other B cell types. Thus, restricted TET2 expression in GC cells may promote type I EBV latency.

Evolution and Cryo-electron Microscopy Capsid Structure of a North American Bat Adenovirus and Its Relationship to Other Mastadenoviruses.

Although many adenoviruses are host specific and likely codiverged with their hosts over millions of years, other adenoviruses appear to have emerged through successful cross-species transmission events on more recent time scales. The wide geographic distribution and genetic diversity of adenoviruses in bats and their close phylogenetic relationship to Canine mastadenovirus A (CAdV A) has raised important questions about how CAdV A, and possibly other mammalian adenoviruses, may have emerged. Although most adenoviruses tend to cause limited disease in their natural hosts, CAdV A is unusual in that it may cause high morbidity and sometimes fatal infections in immunocompetent hosts and is thus an important pathogen of carnivores. Here, we performed a comparative evolutionary and structural study of representative bat and canine adenoviruses to better understand the relationship between these two viral groups.

Hepatitis E virus infection in patients on dialysis and in solid organ transplant recipients in Argentina: exploring associated risk factors.

Infection with hepatitis E virus (HEV) leads to acute hepatitis infection in immunocompetent hosts. HEV genotype 3 can present with high frequency and lead to chronic infection in individuals with a compromised immune system. The risk factors related to increased seroprevalence or chronicity in this population are not entirely understood. Moreover, most studies addressing risk factors for HEV in non-endemic areas come from developed areas such as North America and Europe. In this study we evaluated seroprevalence, chronicity and risk factors for HEV in 120 transplant recipients and 88 patients on dialysis in Argentina. We found a significantly higher seroprevalence of HEV IgG in those undergoing dialysis compared with healthy controls (10.2% and 4.3% respectively, p=0.03). No difference in HEV seroprevalence was observed between healthy controls and transplant recipients (5.8%). We found no association between previously identified risk factors for HEV, such as pork consumption or use of tacrolimus, and HEV seroprevalence. In univariate and multivariate analyses, consumption of fish was associated with higher seroprevalence of HEV (OR=9.33; 95% CI: 2.07-42.2; p=0.04). None of the samples showed HEV RNA amplification, indicating that chronicity does not seem to be an issue in these cohorts. Our results show increased seroprevalence of HEV in individuals undergoing dialysis but not in transplant recipients. We also found that fish consumption can be a potential risk factor for acquiring HEV.

Aeromonas infection from river and playa lake waters in West Texas and southeastern New Mexico

Trauma occurring in direct contact with freshwater bodies may result in wounds contaminated with a variety of microorganisms. Bacteria belonging to the genus Aeromonas have been recovered from these types of infections. We report two cases of Aeromonas hydrophila infections occurring from freshwater-contaminated wounds. One of these infections was acquired from a river in southeastern New Mexico; the other was from an urban playa lake in West Texas. The latter case prompted an ecological study of the seasonal occurrence of Aeromonas spp. and the incidence of resistance to antimicrobial agents in two of these local lakes. Recent scientific and medical literature data show that Aeromonas should be considered as a possible agent of infection in immunocompetent hosts from water exposure, even if the water is a running river or a seemingly unpolluted (“clean”) freshwater lake.

Mucormycosis in Australia: contemporary epidemiology and outcomes

Mucormycosis is the second most common cause of invasive mould infection and causes disease in diverse hosts, including those who are immuno-competent. We conducted a multicentre retrospective study of proven and probable cases of mucormycosis diagnosed between 2004–2012 to determine the epidemiology and outcome determinants in Australia. Seventy-four cases were identified (63 proven, 11 probable). The majority (54.1%) were caused by Rhizopus spp. Patients who sustained trauma were more likely to have non-Rhizopus infections relative to patients without trauma (OR 9.0, p 0.001, 95% CI 2.1–42.8). Haematological malignancy (48.6%), chemotherapy (42.9%), corticosteroids (52.7%), diabetes mellitus (27%) and trauma (22.9%) were the most common co-morbidities or risk factors. Rheumatological/autoimmune disorders occurred in nine (12.1%) instances. Eight (10.8%) cases had no underlying co-morbidity and were more likely to have associated trauma (7/8; 87.5% versus 10/66; 15.2%; p <0.001). Disseminated infection was common (39.2%). Apophysomyces spp. and Saksenaea spp. caused infection in immuno-competent hosts, most frequently associated with trauma and affected sites other than lung and sinuses. The 180-day mortality was 56.7%. The strongest predictors of mortality were rheumatological/autoimmune disorder (OR = 24.0, p 0.038 95% CI 1.2–481.4), haematological malignancy (OR = 7.7, p 0.001, 95% CI 2.3–25.2) and admission to intensive care unit (OR = 4.2, p 0.02, 95% CI 1.3–13.8). Most deaths occurred within one month. Thereafter we observed divergence in survival between the haematological and non-haematological populations (p 0.006). The mortality of mucormycosis remains particularly high in the immuno-compromised host. Underlying rheumatological/autoimmune disorders are a previously under-appreciated risk for infection and poor outcome.

Determination of cytomegalovirus glycoprotein B genotypes in different geographical regions and different patient groups in Turkey

Cytomegalovirus (CMV), a common virus found all around the world, usually causes asymptomatic infections in immunocompetent hosts, however it may lead to serious complications in immunodeficient patients and in the fetus. CMV is divided into four genotypes according to the polymorphisms in UL55 gene that encodes for envelope glycoprotein B. Nucleotide polymorphisms of CMV gB gene can affect the cell tropism of the virus and host immune response and believed to have important changes in the pathogenesis of CMV. The aim of this study was to determine the gB genotypes of CMV isolates from different patient groups selected from different regions of Turkey. A total of 136 clinical specimens from patients (66 female, 70 male; age range: 0-65 years, mean age: 24.03 ± 17.17) who were diagnosed to have CMV infection by polymerase chain reaction (PCR) and/or antigenemia tests, between 2001-2014, in the medical school hospitals of Akdeniz, Ege, Istanbul Cerrahpasa and Erciyes Universities (located at Mediterranean, Aegean, northwest and central Anatolia regions, respectively), were included in the study. The patient group consisted of 80 renal transplant (RT) recipients, 35 stem cell transplant (SCT) recipients, 13 newborns, seven heart transplant (HT) recipients and one pregnant woman. CMV gB genotypes were determined by PCR-RFLP (restriction fragment length polymorphism) method, and DNA sequencing and phylogenetic analysis were performed for the randomly selected 15 isolates with different genotypes. Among 136 (135 plasma, 1 amnion fluid) samples, the most frequent genotype was gB1 (n= 44, 32.4%), followed by gB2 (n= 39, 28.6%), gB3 (n= 36, 26.5%) and gB4 (n= 8, 5.9%); however nine (6.6%) samples could not be genotyped. When analysis were interpreted according to the patient groups, it was determined that the genotypes in RT recipients were gB1 32.3%, gB2 28.7%, gB3 26.5% and gB4 5.9%; in SCT recipients gB1 34.3%, gB2 28.6%, gB3 22.9% and gB4 5.7%; in HT recipients gB3 57.1%, gB1 14.3% and gB2 14.3%; in newborns gB1 38.4%, gB3 30.8%, gB2 15.4% and gB4 7.7%, and gB2 genotype in the pregnant woman. As our study was a descriptive study to determine the genotypes of CMV gB, the relationship between the genotypes and the variants such as viral load, symptomatic disease and prognosis were not analyzed. As a result, the isolation of different gB genotypes in various case groups from four distinctive provinces, underlines the diversity of CMV gB genotypes in Turkey.

Tropical and travel-related dermatomycoses : Part 2: cutaneous infections due to yeasts, moulds, and dimorphic fungi

Besides dermatophytoses, a broad range of cutaneous infections due to yeasts and moulds may occur in subtropical and tropical countries where they can affect travellers. Not to be forgotten are endemic occurring dimorphic or biphasic fungi in countries with hot climate, which cause systemic and secondary cutaneous infections in immunosuppressed and immunocompetent people. In the tropics, the prevalence of pityriasis versicolor, caused by the lipophilic yeast Malassezia spp., is about 30-40 %, in distinct areas even 50 %. Increased hyperhidrosis under tropical conditions and simultaneously humidity congestion have to be considered as significant disposing factors for pityriasis versicolor. In tropical countries, therefore, an exacerbation of a preexisting pityriasis versicolor in travellers is not rare. Today, mostly genital yeast infections due to the new species Candida africana can be found worldwide. Due to migration from Africa this yeast pathogen has reached Germany and Europe. Eumycetomas due to mould fungi are rarely diagnosed in Europe. These deep cutaneous mould infections are only found in immigrants from African countries. The therapy of eumycetoma is protracted and often not successful. Cutaneous cryptococcoses due to the yeast species Cryptococcus neoformans and Cryptococcus gattii occur worldwide; however, they are found more frequently in the tropics. Immunosuppressed patients, especially those with HIV/AIDS, are affected by cryptococcoses. Furthermore, Cryptococcus gattii also causes infections in immunocompetent hosts in Central Africa, Australia, California, and Central America.Rarely found are infections due to dimorphic fungi after travel to countries where these fungal pathogens are endemic. In individual cases, cutaneous or lymphogenic transferred sporotrichosis due to Sporothrix schenkii can occur. Furthermore, scarcely known is secondary cutaneous coccidioidomycosis due to Coccidioides immitis after travelling to desert-like endemic regions in southwestern states of the United States and in Latin America, where primary respiratory infection due to this biphasic fungus can be acquired. The antifungal agent itraconazole is the treatment of choice for sporotrichosis and coccidioidomycosis. Talaromyces marneffei-until recently known as Penicillium marneffei-is only found in Southeastern Asia. Mycosis due to this dimorphic fungus has to be considered as an AIDS-defining opportunistic infection. After hematogeneous spread, Talaromyces marneffei affects the skin and mucous membranes of the mouth. Amphotericin B and itraconazole can be used for therapy.

5(th) International Workshop on CMV and Immunosenescence - A shadow of cytomegalovirus infection on immunological memory.

Human cytomegalovirus (HCMV), a member of the betaherpesvirus family, is an omnipresent pathogen worldwide. Primary HCMV infection elicits robust responses from both the innate and adaptive branches of the immune system. The T-cell response is extraordinary large; on average 10% of the total circulating memory compartment of both the CD4 and CD8 T-cell subsets is specific for HCMV, which makes this virus possibly the most immunogenic microbe for the human immune system. However, despite the extensive immune response, HCMV is not cleared and persists in the host due to its numerous immune evasion mechanisms. Both, primary infection and long-term persistence of HCMV are largely subclinical for the majority of individuals, but HCMV virus is linked to considerable morbidity in immunologically immature and immunocompromised individuals. The role of HCMV infection in immunocompetent hosts has gained considerable interest, and has led to insights that favor a neutral or even beneficial co-existence, but also HCMV-driven detrimental consequences have been reported especially in the elderly. This differential outcome of HCMV infection might be related to the huge variability in the size and phenotype of HCMV-specific T-cell responses among individuals, caused by the differences in infectious dose and the immunocompetence of the host. The interactions between CMV and the immune system were discussed at the 5th International Workshop on CMV and Immunosenescence. Here, we highlight some of the key findings discussed in the meeting, with an emphasis on the particular role of HCMV in memory T-cell formation.

In vitro susceptibility testing of amphotericin B for Cryptococcus neoformans variety grubii AFLP1/VNI and Cryptococcus gattii AFLP6/VGII by CLSI and flow cytometry.

Cryptococcus neoformans var. grubii AFLP1/VNI is the main causative agent of cryptococcosis associated with AIDS in the world. Cryptococcus gattii AFLP6/VGII causes mainly endemic primary infection in immunocompetent hosts. To determine the minimum inhibitory concentrations (MICs) of C. neoformans var. grubii AFLP1/VNI and C. gattii AFLP6/VGII against amphotericin B (AMB) in a short period of time, flow cytometry (FCM) with FUN-1 fluorochrome was used to compare with broth microdilution method (CLSI M27-A3). The minimum incubation period was evaluated by minimum fungicidal concentration procedure. Seventeen clinical isolates of C. neoformans var. grubii AFLP1/VNI and 18 of C. gattii AFLP6/VGII were analysed. The time for the determination of MICs by FCM was 2 h against 72 h by CLSI M27-A3 and the comparison of MIC showed a positive significant correlation (P = 0.048). It is important to highlight the role of the FCM as an alternative method to determine the MICs for AMB in within a day, with positive cost-benefit.

Dermatophytes activate skin keratinocytes via mitogen-activated protein kinase signaling and induce immune responses.

Dermatophytes cause superficial and cutaneous fungal infections in immunocompetent hosts and invasive disease in immunocompromised hosts. However, the host mechanisms that regulate innate immune responses against these fungi are largely unknown. Here, we utilized commercially available epidermal tissues and primary keratinocytes to assess (i) damage induction by anthropophilic, geophilic, and zoophilic dermatophyte strains and (ii) the keratinocyte signaling pathways, transcription factors, and proinflammatory responses induced by a representative dermatophyte, Trichophyton equinum. Initially, five dermatophyte species were tested for their ability to invade, cause tissue damage, and induce cytokines, with Microsporum gypseum inducing the greatest level of damage and cytokine release. Using T. equinum as a representative dermatophyte, we found that the mitogen-activated protein kinase (MAPK) pathways were predominantly affected, with increased levels of phospho-p38 and phospho-Jun N-terminal protein kinase (JNK) but decreased levels of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2). Notably, the NF-κB and PI3K pathways were largely unaffected. T. equinum also significantly increased expression of the AP-1-associated transcription factor, c-Fos, and the MAPK regulatory phosphatase, MKP1. Importantly, the ability of T. equinum to invade, cause tissue damage, activate signaling and transcription factors, and induce proinflammatory responses correlated with germination, indicating that germination may be important for dermatophyte virulence and host immune activation.

Hospital-acquired pneumonia due to Leclercia adecarboxylata in a neurosurgical centre

Leclercia adecarboxylata, a gram-negative bacillus of the Enterobacteriaceae family, is an uncommonly identified human pathogen. The organism has been reported worldwide and isolated from various environmental sources. Most human infections are polymicrobial and commonly occur in immunocompromised hosts, although nosocomial infections in immunocompetent hosts have been documented. We describe three case reports of L. adecarboxylata isolation from cases of hospital acquired pneumonia admitted to a tertiary care center for neurosurgical care.

Cepacia Syndrome in a Non-Cystic Fibrosis Patient.

Burkholderia (formerly Pseudomonas) cepacia complex is a known serious threat to patients with cystic fibrosis, in whom it has the potential to cause the fatal combination of necrotizing pneumonia, worsening respiratory failure, and bacteremia, known as Cepacia syndrome. The potential for this pathogen to infect non-cystic fibrosis patients is limited and its epidemiology is poorly understood. Previously reported cases of severe Burkholderia cepacia complex lung infection in immunocompetent hosts include pneumonia, bronchiectasis, pyopneumothorax, and cavitary lesions. We present a case of a 64-year-old man with Streptococcus pneumoniae community-acquired pneumonia whose hospital course was complicated by developing cavitary lung lesions, bacteremia, and acute respiratory distress syndrome. Repeated tracheal aspirate and blood cultures grew Burkholderia cepacia. Our case appears to be the first report of Cepacia syndrome in a patient without cystic fibrosis. This report raises concern regarding the potential severity of pulmonary Burkholderia cepacia complex infection and the need to broaden clinicians' suspicion for Cepacia syndrome. A framework to help diagnose and treat infected non-cystic fibrosis individuals may be useful.

Achromobacter xylosoxidans: A Rare Infection Masquerading as Metastatic Hepatic Malignancy

Introduction: The incidence of pyogenic liver abscesses is estimated to be 3.6 per 100,000 in the United States. Achromobacter xylosoxidans (AX) is an aerobic, motile, gram-negative bacillus, often misidentified as Pseudomonas aeruginosa, that can be isolated in hospital and domestic sink drains. Bacteremia and bronchiolitis due to AX has been described in patients after liver transplantation for Caroli’s disease and cystic fibrosis, respectively. Although it may be found occasionally in the bile, it is very rarely the cause of liver abscess in immunocompetent patients. Rare cases of liver and intraabdominal abscesses caused by AX have been described in association with prior cholecystectomy. We describe a rare case of AX infection mimicking hepatic malignancy in an immunocompetent patient after cholecystectomy and ERCP. A 66-year-old female with history of open cholecystectomy for gangrenous cholecystitis, ERCP for gallstone pancreatitis, PPD+, and recent colonoscopy with polypectomy, was admitted for right upper quadrant abdominal pain, nausea, and weight loss. Laboratory work-up showed WBC count of 13 with 77% neutrophils, platelets 575, total bilirubin of 1.4 mg/dL, and alkaline phosphatase 255 U/L. CT of the abdomen revealed 2 solid masses in the liver. CEA, CA 19-9, AFP, and CA-125 were normal. CT of chest showed only emphysematous changes. Two needle liver biopsies showed fibroinflammatory tissue with focal necrotizing granulomas, and large droplet steatosis, compatible with an infectious process suggestive of AX. The patient was treated with sulfamethoxazole/trimethoprim 800/160 mg, and within 2 weeks, she demonstrated significant improvement in appetite and weight gain. After 6 weeks of therapy, she was asymptomatic with complete resolution of the lesions on repeat MRI. While AX is a ubiquitous waterborne nosocomial organism, it rarely causes infections in immunocompetent hosts. Hepatic involvement may mimic metastatic malignancy and may pose additional diagnostic challenges. It is important to be cognizant of this rare cause of liver abscess in immunocompromized and immunocompetent patients after cholecystectomy and ERCP.

Localized cutaneous infections in immunocompetent individuals due to rapidly growing mycobacteria.

Rapidly growing mycobacteria (RGM) cause skin infections that are refractory to standard antibiotic regimens. Although typically associated with disseminated cutaneous or other systemic infections in immunocompromised patients, RGM sometimes cause localized cutaneous infections in immunocompetent hosts. These infections are almost always associated with precedent skin trauma and inoculation, and therefore have been implicated in outbreaks involving contaminated tattoo ink and inadequately sterilized acupuncture needles. Histologic features often include suppurative granulomatous inflammation, and microorganisms are rarely visualized with stains for acid-fast bacilli. The differential diagnosis includes granulomatous fungal and non-RGM bacterial infections as well as noninfectious suppurative or sarcoidlike conditions. Because no pathognomonic histologic features exist for cutaneous RGM infections, clinical suspicion and appropriate workup are essential to reach an accurate and timely diagnosis. Most localized cutaneous RGM infections in immunocompetent individuals respond well to either clarithromycin or amikacin, in combination with surgical debridement.

Clinical and Morphologic Findings in Disseminated Scedosporium Apiospermum Infections in Immunocompromised Patients

Scedosporium apiospermum is a ubiquitous, saprophytic, filamentous mold that may cause localized, subcutaneous infections in immunocompetent hosts, but disseminated infection in severely immunocompromised patients. This mold is often highly resistant to multiple commonly used antifungal drugs. Even with treatment, there is a high mortality rate. We present two patients with fatal disseminated S. apiospermum infections after bone marrow and lung transplantation. This infection can be rapidly fatal, and survival may be improved by early recognition.