In vitro antifungal susceptibility of Candida spp. isolates from patients with chronic periodontitis and from control patients

Superinfection by Candida can be refractory to conventional periodontal treatments in specific situations, such as in immunocompromised patients. In these cases, the systemic therapy with antifungal drugs could be indicated. The aim of this study was to analyse antifungal susceptibility of Candida spp. strains isolated from chronic periodontitis patients and from control individuals. A total of 39 C. albicans isolates, 9 C. tropicalis, 2 C. glabrata and 5 Candida spp. from control individuals and 30 C. albicans, 3 C. tropicalis and 2 C. glabrata from periodontitis patients were tested. In the control group, 1 isolate of C. glabrata was resistant to ketoconazole and 1 Candida spp. was resistant to amphotericin B, ketoconazole and miconazole. Among the isolates of periodontitis group, 1 (3.33%) C. albicans isolate was resistant to flucytosine and ketoconazole. According to the obtained results, it could be concluded that fluconazole was the most effective drug against the several Candida species studied. There were not expressive differences in the susceptibility of isolates from periodontitis patients or from control individuals.

Outcomes in patients waiting for antiretroviral treatment in the Free State Province, South Africa: prospective linkage study

Objective: In South Africa, many HIV-infected patients experience delays in accessing antiretroviral therapy (ART). We examined pretreatment mortality and access to treatment in patients waiting for ART. Design: Cohort of HIV-infected patients assessed for ART eligibility at 36 facilities participating in the Comprehensive HIV and AIDS Management (CHAM) program in the Free State Province. Methods: Proportion of patients initiating ART, pre-ART mortality and risk factors associated with these outcomes were estimated using competing risks survival analysis. Results: Forty-four thousand, eight hundred and forty-four patients enrolled in CHAM between May 2004 and December 2007, of whom 22 083 (49.2%) were eligible for ART; pre-ART mortality was 53.2 per 100 person-years [95% confidence interval (CI) 51.8–54.7]. Median CD4 cell count at eligibility increased from 87 cells/ml in 2004 to 101 cells/ml in 2007. Two years after eligibility an estimated 67.7% (67.1–68.4%) of patients had started ART, and 26.2% (25.6–26.9%) died before starting ART. Among patients with CD4 cell counts below 25 cells/ml at eligibility, 48% died before ART and 51% initiated ART. Men were less likely to start treatment and more likely to die than women. Patients in rural clinics or clinics with low staffing levels had lower rates of starting treatment and higher mortality compared with patients in urban/peri-urban clinics, or better staffed clinics. Conclusions: Mortality is high in eligible patients waiting for ART in the Free State Province. The most immunocompromised patients had the lowest probability of starting ART and the highest risk of pre-ART death. Prioritization of these patients should reduce waiting times and pre-ART mortality.

Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3)

Mucormycosis is an emerging cause of infectious morbidity and mortality in patients with hematologic malignancies. However, there are no recommendations to guide diagnosis and management. The European Conference on Infections in Leukemia assigned experts in hematology and infectious diseases to develop evidence-based recommendations for the diagnosis and treatment of mucormycosis. The guidelines were developed using the evidence criteria set forth by the American Infectious Diseases Society and the key recommendations are summarized here. In the absence of validated biomarkers, the diagnosis of mucormycosis relies on histology and/or detection of the organism by culture from involved sites with identification of the isolate at the species level (no grading). Antifungal chemotherapy, control of the underlying predisposing condition, and surgery are the cornerstones of management (level A II). Options for first-line chemotherapy of mucormycosis include liposomal amphotericin B and amphotericin B lipid complex (level B II). Posaconazole and combination therapy of liposomal amphotericin B or amphotericin B lipid complex with caspofungin are the options for second line-treatment (level B II). Surgery is recommended for rhinocerebral and skin and soft tissue disease (level A II). Reversal of underlying risk factors (diabetes control, reversal of neutropenia, discontinuation/taper of glucocorticosteroids, reduction of immunosuppressants, discontinuation of deferroxamine) is important in the treatment of mucormycosis (level A II). The duration of antifungal chemotherapy is not defined but guided by the resolution of all associated symptoms and findings (no grading). Maintenance therapy/secondary prophylaxis must be considered in persistently immunocompromised patients (no grading).

Disseminated Mycobacterium marinum infection with extensive cutaneous eruption and bacteremia in an immunocompromised patient

Mycobacterium marinum can cause fish tank granuloma (or swimming pool or aquarium granuloma) in immunocompetent patients. Dissemination of Mycobacterium marinum-infection is a rare condition which occurs mainly in immunocompromised patients and can be life-threatening. We report the case of an 87-year-old woman who was treated with oral corticosteroids for polymyalgia rheumatica for many years and developed erythema nodosum-like lesions on the right forearm and arthritis of the right wrist. By increasing the steroid dosage and adding methotrexate only short-term remission was achieved. Seven months later painful erythematous nodules occurred on all extremities which became necrotic, ulcerative and suppurative. Ziehl-Neelsen staining revealed acid-fast bacilli and Mycobacterium marinum was cultured from skin biopsies, blood, and urine. The critically ill patient was treated with clarithromycin and ethambutol resulting in a dramatic improvement of the general condition. After four months, doxycycline had to be added because of new skin lesions. This case illustrates the impact of Mycobacterium marinum infection in immunocompromised patients.

AIDS defining opportunistic infections in patients with high CD4 counts in the combination antiretroviral therapy (cART) era: things ain't what they used to be.

INTRODUCTION According to reports from observational databases, classic AIDS-defining opportunistic infections (ADOIs) occur in patients with CD4 counts above 500/µL on and off cART. Adjudication of these events is usually not performed. However, ADOIs are often used as endpoints, for example, in analyses on when to start cART. MATERIALS AND METHODS In the database, Swiss HIV Cohort Study (SHCS) database, we identified 91 cases of ADOIs that occurred from 1996 onwards in patients with the nearest CD4 count >500/µL. Cases of tuberculosis and recurrent bacterial pneumonia were excluded as they also occur in non-immunocompromised patients. Chart review was performed in 82 cases, and in 50 cases we identified CD4 counts within six months before until one month after ADOI and had chart review material to allow an in-depth review. In these 50 cases, we assessed whether (1) the ADOI fulfilled the SHCS diagnostic criteria (www.shcs.ch), and (2) HIV infection with CD4 >500/µL was the main immune-compromising condition to cause the ADOI. Adjudication of cases was done by two experienced clinicians who had to agree on the interpretation. RESULTS More than 13,000 participants were followed in SHCS in the period of interest. Twenty-four (48%) of the chart-reviewed 50 patients with ADOI and CD4 >500/µL had an HIV RNA <400 copies/mL at the time of ADOI. In the 50 cases, candida oesophagitis was the most frequent ADOI in 30 patients (60%) followed by pneumocystis pneumonia and chronic ulcerative HSV disease (Table 1). Overall chronic HIV infection with a CD4 count >500/µL was the likely explanation for the ADOI in only seven cases (14%). Other reasons (Table 1) were ADOIs occurring during primary HIV infection in 5 (10%) cases, unmasking IRIS in 1 (2%) case, chronic HIV infection with CD4 counts <500/µL near the ADOI in 13 (26%) cases, diagnosis not according to SHCS diagnostic criteria in 7 (14%) cases and most importantly other additional immune-compromising conditions such as immunosuppressive drugs in 14 (34%). CONCLUSIONS In patients with CD4 counts >500/ µL, chronic HIV infection is the cause of ADOIs in only a minority of cases. Other immuno-compromising conditions are more likely explanations in one-third of the patients, especially in cases of candida oesophagitis. ADOIs in HIV patients with high CD4 counts should be used as endpoints only with much caution in studies based on observational databases.

Comprehensive environmental study in high risk areas for cancer patients comparing air and water Aspergillus species samples

Background. Nosocomial invasive aspergillosis (a highly fatal disease) is an increasing problem for immunocompromised patients. Aspergillus spp. can be transmitted via air (most commonly) and by water. ^ The hypothesis for this prospective study was that there is an association between patient occupancy, housekeeping practices, patients, visitors, and Aspergillus spp. loading. Rooms were sampled as not terminally cleaned (dirty) and terminally cleaned (clean). The secondary hypothesis was that Aspergillus spp. positive samples collected from more than one sampling location within the same patient room represent the same isolate. ^ Methods. Between April and October 2004, 2873 environmental samples (713 air, 607 water, 1256 surface and 297 spore traps) were collected in and around 209 “clean” and “dirty” patient rooms in a large cancer center hospital. Water sources included aerosolized water from patient room showerheads, sinks, drains, and toilets. Bioaerosol samples were from the patient room and from the running shower, flushing toilet, and outside the building. The surface samples included sink and shower drains, showerheads, and air grills. Aspergillus spp. positive samples were also sent for PCR, molecular typing (n = 89). ^ Results. All water samples were negative for Aspergillus spp. There were a total of 130 positive culturable samples (5.1%). The predominant species found was Aspergillus niger. Of the positive culturable samples, 106 (14.9%) were air and 24 (3.8%) were surface. There were 147 spore trap samples, and 49.5% were positive for Aspergillus/Penicillum spp. Of the culturable positive samples sent for PCR, 16 were indistinguishable matches. There was no significant relationship between air and water samples and positive samples from the same room. ^ Conclusion. Primarily patients, visitors and staff bring the Aspergillus spp. into the hospital. The high number of A. niger samples suggests the spores are entering the hospital from outdoors. Eliminating the materials brought to the patient floors from the outside, requiring employees, staff, and visitors to wear cover up over their street clothes, and improved cleaning procedures could further reduce positive samples. Mold strains change frequently; it is probably more significant to understand pathogenicity of viable spores than to commit resources on molecular strain testing on environmental samples alone. ^

Respiratory syncytial virus infection in hematopoietic stem cell transplant patients

Respiratory Syncytial Virus (RSV) is a major cause of respiratory tract infections in immunocompromised patients such as children less than 2 years, premature infants with congenital heart disease and chronic lung disease, elderly patients and patients who have undergone hematopoietic stem cell transplant (HSCT). HSCT patients are at high risk of RSV infection, at increased risk of developing pneumonia, and RSV-related mortality. Immunodeficiency can be a major risk factor for severe infection & mortality. Therapy of RSV infection with Ribavirin, Palivizumab and Immunoglobulin has shown to reduce the risk of progression to LRI and mortality, especially if initiated early in the disease. Data on RSV infection in HSCT patients is limited, especially at various levels of immunodeficiency. 323 RSV infections in HSCT patients have been identified between 1/1995 and 8/2009 at University of Texas M D Anderson Cancer Center (UTMDACC). In this proposed study, we attempted to analyze a de-identified database of these cases and describe the epidemiologic characteristics of RSV infection in HSCT patients, the course of the infection, rate of development of pneumonia and RSV-related mortality in HSCT patients at UTMDACC.^ Key words: RSV infections, HSCT patients ^

Clostridium difficile infection (CDI) in HIV-positive patients

The main aim of this study was to look at the association of Clostridium difficile infection (CDI) and HIV. A secondary goal was to look at the trend of CDI-related deaths in Texas from 1999-2011. To evaluate the coinfection of CDI and HIV, we looked at 2 datasets provided by CHS-TDSHS, for 13 years of study period from 1999-2011: 1) Texas death certificate data and 2) Texas hospital discharge data. An ancillary source of data was national level death data from CDC. We did a secondary data analysis and reported the age-adjusted death rates (mortality) and hospital discharge frequencies (morbidity) for CDI, HIV and for CDI+HIV coinfection.^ Since the turn of the century, CDI has reemerged as an important public health challenge due to the emergence of hypervirulent epidemic strains. From 1999-2011, there has been a significant upward trend in CDI-related death rates; in the state of Texas alone, CDI mortality rate has increased 8.7 fold in this time period at the rate of 0.2 deaths per year per 100,000 individuals. On the contrary, mortality due to HIV has decreased by 46% and has been trending down. The demographic groups in Texas with the highest CDI mortality rates were elderly aged 65+, males, whites and hospital inpatients. The epidemiology of C. difficile has changed in such a way that it is not only staying confined to these traditional high-risk groups, but is also being increasingly reported in low-risk populations such as healthy people in the community (community acquired C. difficile), and most recently immunocompromised patients. Among the latter, HIV can worsen the adverse health outcomes of CDI and vice versa. In patients with CDI and HIV coinfection, higher mortality and morbidity was found in young & middle-aged adults, blacks and males, the same demographic population that is at higher risk for HIV. As with typical CDI, the coinfection was concentrated in the hospital inpatients. Of all the CDI-related deaths in USA from 1999-2010, in the 25-44 year age group, 13% had HIV infection. Of all CDI-related inpatient hospital discharges in Texas from 1999-2011, in patients 44 years and younger, 17% had concomitant HIV infection. Therefore, HIV is a possible novel emerging risk factor for CDI.^

Endocarditis By Kocuria Rosea In An Immunocompetent Child.

Kocuria rosea belongs to genus Kocuria (Micrococcaceae family, suborder Micrococcineae, order Actinomycetales) that includes about 11 species of bacteria. Usually, Kocuria sp are commensal organisms that colonize oropharynx, skin and mucous membrane; Kocuria sp infections have been described in the last decade commonly affecting immunocompromised patients, using intravenous catheter or peritoneal dialysis. These patients had mainly bacteremia/recurrent sepsis. We hereby describe the case of a 10-year-old girl, immunocompetent, who had endocarditis/sepsis by K. rosea which was identified in five different blood cultures by Vitek 2 ID-GPC card (BioMérieux, France). Negative HIV serology, blood count within normal range of leukocytes/neutrophils and lymphocytes, normal fractions of the complement, normal level of immunoglobulins for the age; lymphocyte immunophenotyping was also within the expected values. Thymus image was normal at chest MRI. No catheters were required. Identification of K. rosea was essential to this case, allowing the differentiation of coagulase-negative staphylococci and use of an effective antibiotic treatment. Careful laboratory analysis of Gram-positive blood-born infections may reveal more cases of Kocuria sp infections in immunocompetent patients, which may collaborate for a better understanding, prevention and early treatment of these infections in pediatrics.

Infectious endocarditis caused by Nocardia sp.: histological morphology as a guide for the specific diagnosis

Nocardia is a rare opportunistic agent, which may affect immunocompromised individuals causing lung infections and exceptionally infective endocarditis (IE). There are few reports of IE caused by Nocardia sp., usually involving biological prostheses but rarely in natural valves. Its accurate microbiological identification may be hampered by the similarity with Rhodococcus equi and Corynebacterium spp. Here we report a case of native mitral valve IE caused by this agent in which the clinical absence of response to vancomycin and the suggestion of Nocardia sp. by histology pointed to the misdiagnosis of Corynebacterium spp. in blood cultures. The histological morphology can advise on the need for expansion of cultivation time and use of extra microbiological procedures that lead to the differential diagnosis with Corynebacterium spp. and other agents, which is essential to establish timely specific treatment, especially in immunocompromised patients.

Serological Survey for Antibodies to Encephalitozoon cuniculi in Ownerless Dogs From Urban Areas of Brazil and Colombia

There are 3 strains of Encephalitozoon cuniculi that occur in mammals. Strain III is associated with clinical disease in dogs, although some can be asymptomatic carriers and excrete spores in their urine. Several cases of human E. cuniculi infection caused by strain III have been observed in immunocompromised patients, indicating that E. cuniculi should be considered a zoonotic agent. Encephalitozoon cuniculi can cause fatal disease in maternally-infected or young dogs. Clinical signs in these animals included blindness, encephalitis, retarded growth rate, and nephritis. Encephalitozoon cuniculi has also been associated with primary renal failure in adult dogs. The present study used the direct agglutination test (DAT, cut-off 1:50) and the indirect fluorescent antibody test (IFAT, cut-off 1:10) to examine the prevalence of antibodies to E. cuniculi in dogs from Brazil and Colombia. Using the DAG, 31 (27.4%) of 113 dogs from Brazil and 47 (18.5%) of 254 dogs from Colombia were seropositive. Nine (14.3%) of 63 dogs from Brazil and IS (35.3%) of the 51 dogs from Colombia were seropositive by indirect immunofluorescent antibody test. These results indicate that dogs from Brazil and Colombia are exposed to E. cuniculi.

Cytokines in the oral mucosa of mice infected with Candida albicans

Oropharyngeal candidiasis is associated with defects in cell-mediated immunity, and is commonly seen in immunocompromised patients. We have previously shown that T-cell-deficient BALB/c nude (nu/nu) mice are extremely susceptible to oropharyngeal candidiasis, and that recovery from a chronic infection is dependent on CD4 T lymphocytes. In this study we describe the local tissue cytokine profile in lymphocyte-reconstituted immunodeficient mice and their euthymic counterparts. Mice were infected orally with 10(8) cells of the yeast Candida albicans , and oral tissues sampled on days 0, 4, 8, and 14. Nude mice were reconstituted with 3 x 10(7) naive lymphocytes following oral inoculation. Interleukin (IL)-6, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha were identified in the oral tissues of infected euthymic mice recovering from oral infection, as well as naive controls. TNF-alpha was identified in nude oral tissue on days 4 and 8, but only after lymphocyte reconstitution. No IL-2, IL-4 or IL-10 was detected in either euthymic or athymic mice at any time-point throughout the experiment. This study confirms the functional activity of T lymphocytes in reconstituted nude mice, and suggests that TNF-alpha may be an important mediator in the recovery from oropharyngeal candidiasis.

Cutaneous Mycobacterium haemophilum infection in a kidney transplant recipient after acupuncture treatment

P>Mycobacterium haemophilum is a slow-growing nontuberculous mycobacterium that can cause disease in both immunocompetent and immunocompromised patients. The most common clinical presentations of infection are the appearance of suppurative and ulcerated skin nodules. For the diagnosis, samples collected from suspected cases must be processed under the appropriate conditions, because M. haemophilum requires lower incubation temperatures and iron supplementation in order to grow in culture. In this case report, we describe the occurrence of skin lesions in a kidney transplant recipient, caused by M. haemophilum, associated with acupuncture treatment. The diagnosis was established by direct smear and culture of material aspirated from cutaneous lesions. Species identification was achieved by characterization of the growth requirements and by partial sequencing of the hsp65 gene. The patient was successfully treated with clarithromycin and ciprofloxacin for 12 months. Considering that the number of patients receiving acupuncture treatment is widely increasing, the implications of this potential complication should be recognized, particularly in immunosuppressed patients.

Case Report: Esophageal Histoplasmosis Associated with Disseminated Tuberculosis in Acquired Immunodeficiency Syndrome

Bacterial and fungal infections are common in acquired immunodeficiency syndrome (AIDS). Histoplasmosis is a common fungal disease in severely immunocompromised patients infected with human immunodeficiency virus (HIV) in endemic areas. In this population the most frequent form of presentation of histoplasmosis is disseminated, with the clinical manifestations being similar to those of disseminated tuberculosis. Esophageal histoplasmosis and the association of histoplasmosis with tuberculosis are infrequent. We report here a rare Case of esophageal histoplasmosis associated with disseminated tuberculosis in AIDS.

Human cryptosporidiosis: detection of specific antibodies in the serum by an indirect immunofluorescence

Cryptosporidium sp., a coccidian parasite usually found in the faeces of cattle, has been recently implicated as an agent of human intestinal disease, mainly in immunocompromised patients. In the study realized, by an indirect immunofluorescence technique, specific immunoglobulins (IgG and IgM) have been demonstrated in human serum against Cryptosporidium oocysts. Purified oocysts were used as antigens in the indirect immunofluorecence assay. After analyzing this test in sera from selected groups of patients, the frequency of both specific IgG and IgM of immunocompetent children who were excreting oocysts in their faeces was 62% and in children with negative excretion of oocysts was 20% and 40%, respectively. In adults infected with the human immunodeficiency virus (HIV) and who were excreting Cryptosporidium in their stools, the frequency was 57% for IgG but only 2% for IgM. Twenty three percent of immunocompromised adults with not determined excretion of oocysts in their stools had anti-Cryptosporidium IgG in their sera. Children infected with human immunodeficiency virus had no IgM and only 14% had IgG detectable in their sera. The indirect immunoflorescence assay, when used with other parasitological techniques appears to be useful for retrospective population studies and for diagnosis of acute infection. The humoral immune response of HIV positive patients to this protozoan agent needs clarification.