Oral candidal carriage and infection in insulin-treated diabetic patients.

AIM: To evaluate candidal load and carriage of candidal species in 414 insulin-treated diabetes mellitus patients with and without clinical signs of infection. Host factors that could influence candidal load in diabetic patients with oral candidosis were also investigated. METHODS: Candidal species were recovered from 414 insulin-treated diabetes mellitus patients attending two hospital diabetic clinics, using an oral rinse technique. RESULTS: Seventy-seven per cent of diabetic patients carried Candida species in their oral cavity, with C. albicans being the species most frequently isolated. C. dubliniensis was found for the first time in this patient group. Forty per cent of patients colonized with candidal species had no clinical signs of oral candidosis. Where oral candidosis was present, erythematous candidosis was the most common clinical presentation. Candidal load was not associated with age, sex or glycaemic control. However, it was significantly increased in those patients who were tobacco smokers, and non-significantly increased in those patients who wore dentures, or who had clinical signs of oral candidosis. CONCLUSION: The epidemiology of oral candidal carriage and infections in diabetic patients is complex and includes species which have not been previously reported in this group of patients. The development of oral candidosis in insulin-treated diabetes mellitus patients is not the result of a single entity, but rather, a combination of risk factors.     

Oral candida albicans in HIV infection

The prevalence of oral colonization with Candida albicans was studied in 225 homosexual men, 99 of whom had HIV antibodies and in 175 heterosexual men. Oral candidal carriage was most prevalent among HIV seropositive homosexual men (77.8%). Rich growth of C. albicans in culture and findings of pseudomycelial elements in oral mucosal smear also correlated with HIV seropositivity. Pseudomycelial forms of C. albicans were demonstrated in mucosal smear from all patients with oral mucosal lesions suspected for candidiasis. However, 26/53 patients (49.1%) with positive smear had no clinical signs of oral candidiasis. The oral yeast flora was sampled twice in 85 homosexual men at an interval of 12-18 months. 71/85 patients (83.5%) were grouped into the same category of candidal colonization; carrier or noncarrier state, on both occasions. No statistically significant differences in numbers of CD 4 cells or CD 8 cells were observed between patients with respect to candidal colonization, when HIV seropositive and seronegative homosexual men were considered separately.     

Asymptomatic oral carriage of Candida species in HIV-infected patients in the highly active antiretroviral therapy era

Oropharyngeal candidiasis is the most common opportunistic fungal infection in individuals infected with human immunodeficiency virus. CD4+ lymphocytes count and the quantification of viral RNA in blood plasma have been found to be the main markers of HIV disease progression. The present study was conducted to evaluate Candida sp. diversity in the oral cavity of HIV-infected patients and to determine whether there was association of CD4+ cell count and viral load with asymptomatic oral Candida carriage. Out of 99 HIV-positive patients studied, 62 (62.6%) had positive culture for Candida (oral carriage) and 37 patients (37.4%) had Candida negative culture (no oral carriage). The etiologic agents most common were C. albicans and C. tropicalis. The range of CD4+ was 6-2305 cells/mm3 in colonized patients and 3-839 cells/mm3 for non-colonized patients, while the viral load was 60-90016 copies/mL for colonized patients and 75-110488 copies/mL for non colonized patients. The viral load was undetectable in 15 colonized patients and in 12 non colonized patients. Our results showed that there was no significant difference of the variables CD4+ cell count and viral load between oral candida carriage and no oral candida carriage patients.     

Urinary tract infections due to Candida albicans

Infection of the urinary tract due to Candida albicans is an uncommon but well-described complication of modern therapeutics. Despite the rarity of this infection, culture of properly collected urine yielding C. albicans requires an explanation. The significance of systemic factors in the defense of the urinary tract against candidal infection is unknown, but secretions from the prostate gland in men and from periurethral glands in women have been reported to be fungistatic. In addition, growth of Candida at sites on mucous membranes may be suppressed by other normal flora. Conditions that predispose to candiduria include diabetes mellitus, antibiotic and corticosteroid therapy, as well as factors such as local physiology and disturbance of urine flow. Lower urinary tract candidiasis is usually the result of a retrograde infection, while renal parenchymal infection most often follows candidemia. In addition to asymptomatic candiduria, recognized clinical forms of candidal urinary tract infections include bladder infection, renal parenchymal infection, and infections associated with fungus ball formation. Unfortunately, clinical criteria alone are insufficient to distinguish reliably among these clinical types. If the urine is found to contain candidal organisms, the condition of the patient should be considered for determination of appropriate therapy. When infection is thought to be confined to the bladder, patients without indwelling bladder catheters should be considered for flucytosine therapy. For patients requiring indwelling bladder catheterization, irrigation with amphotericin B is usually successful. Although flucytosine alone may be useful for renal parenchymal candidal infection, iv amphotericin B alone or the combination of amphotericin B and flucytosine is indicated when systemic candidiasis cannot be excluded.     

Methicillin-resistant Staphylococcus aureus (MRSA) isolation from diabetic foot ulcers correlates with nasal MRSA carriage

Methicillin-resistant Staphylococcus aureus is increasingly isolated from diabetic foot ulcers, and may be associated with an adverse prognosis. We have explored the relationship between MRSA isolation from foot ulcers and nasal MRSA carriage. Over a 12 month period, 65 consecutively attending patients with diabetic foot ulceration were recruited. Demographic information was collected, and the ulcer and nose swabbed bacteriologically using standard techniques. The patients were mean age 61 year, diabetes duration 14 year, and HbA1c 8.5%. There were 61% male and 85% with type 2 diabetes. Ulcers were neuropathic in 55%, ischaemic in 14% and neuroischaemic in 31%. MRSA was isolated from 12 (19%) ulcers, and 11 (17%) had nasal carriage. Of the MRSA positive ulcer patients 7/12 (58%) had nasal MRSA carriage, compared with 4/53 (8%) with MRSA negative ulcers (p<0.0003). We conclude that nasal MRSA carriage in diabetic patients is a significant risk factor for foot ulcer MRSA infection.     

Staphylococcus aureus nasal carriage in hemodialysis patients. Its role in infection and approaches to prophylaxis

Staphylococcus aureus infections remain a major cause of morbidity in hemodialysis patients. Chronic dialysis patients are more prone to staphylococcal infections because of their decreased immunity, increased skin colonization by staphylococci, and the multiple needle punctures required for dialysis. The source of the staphylococci is the anterior nares. Elimination of staphylococcal nasal carriage results in a significantly lower infection rate. Selected clinical studies of topical and oral therapy for eradication of staphylococcal nasal carriage are reviewed. Rifampin has been the most consistently efficacious agent, although emergence of resistance is a potential problem. Trials utilizing newer topical and oral agents for prophylactic eradication of S aureus from the nose are indicated. Promising antibiotics include topical mupirocin, the oral quinolones, and clindamycin.     

Serologic diagnosis of systemic candidiasis in patients with acute leukemia

Serum precipitin and agglutinin reactions against Candida albicans were measured in eight patients with acute leukemia in whom clinical signs suggested secondary systemic candidiasis. The reliability of the serodiagnostic methods was evaluated by antemortem and/or postmortem evidence of systemic candidal infection. “True positive” precipitin reactions concomitant with increased serum agglutinin titers were observed in six of eight patients who had extensive candidal lesions on postmortem examination. Two “false negative” precipitin reactions were noted. Eleven additional patients in whom the precipitin reaction was negative and in whom agglutinin titers did not exceed 1:40 were free of candidal infection at autopsy.     

Oral carriage of staphylococci in patients with rheumatoid arthritis.

OBJECTIVE: To determine the prevalence of oral staphylococcal carriage in patients with rheumatoid arthritis compared with healthy controls. METHODS: Fifty healthy adults, 25 healthy elderly volunteers and 25 patients with rheumatoid arthritis were studied. An oral rinse, tongue swab and nasal swab were collected for culture on blood agar and a range of selective agars. Isolates of staphylococci were identified and antibiotic sensitivity profiles determined by standard methods. RESULTS: Staphylococci were isolated from the mouths of 94% of the healthy adults, 24% of whom carried Staphylococcus aureus. All the healthy elderly carried oral staphylococci and 36% were colonized with S. aureus. Staphylococci were isolated from 96% of the rheumatoid arthritis patients and this group had the highest carriage rate of S. aureus (56%), significantly higher than the healthy adults (P < 0.05). In all three groups, Staphylococcus epidermidis was isolated from the mouths of > 80%. No methicillin-resistant strains of S. aureus were isolated. CONCLUSION: Oral carriage of S. aureus appears to be common in patients with rheumatoid arthritis and studies of the mouth as a source of infection in septic arthritis would be merited.     

Oropharyngeal gram-negative bacillary carriage in chronic obstructive pulmonary disease: relation to severity of disease.

The prolonged presence of aerobic Gram-negative bacilli (AGNB) in the oropharynx is termed 'carriage'. AGNB carriage rates are low in populations of healthy individuals. Previously, severity of underlying disease has been positively correlated with oropharyngeal AGNB carriage rate. Overgrowth of AGNB at the oropharynx poses a significant risk of endogenous infection in end-stage chronic obstructive pulmonary disease (COPD) patients. The aims of this study were to undertake an epidemiological survey of the oropharyngeal flora of COPD patients and to correlate oropharyngeal carriage of AGNB with severity of disease. Two oral rinses were obtained, within a 2-day interval, from 40 COPD patients comprising three disease severity groups: 1. mild, 2. moderate and 3. severe. Eighty oral rinses were quantitatively (1:10 dilution series) cultured for AGNB and yeasts using broth enrichment. The mean AGNB carriage rate was 15%. AGNB carriage rates of 0, 7.7 and 29.4% were observed within the mild, moderate and severe disease groups, respectively. The mean yeast carriage rate was 33.3%. Yeast carriage rates of 33.3, 15.4 and 64.7% were observed within the mild, moderate and severe disease groups, respectively. Carriage of Staphylococcus aureus was 5%. Rates of oropharyngeal carriage of AGNB (1/23 vs. 5/17) and yeasts (5/23 vs. 11/17) were significantly higher within the severe disease group than in non-severe disease groups. Oropharyngeal carriage of AGNB in end-stage COPD patients (forced expiratory volume in 1 sec, FEV1 < 50% predicted) presents a potential source of Gram-negative endogenous pneumonia. This outcome may be promoted by intubation and some flora-suppressing antibiotic therapies.     

Candida spondylodiscitis and epidural abscess: management with shorter courses of anti-fungal therapy in combination with surgical debridement

Epidural abscess associated with candidal spondylodiscitis is rarely seen, particularly when it involves the cervical and thoracic spine. We report two such cases that were successfully managed with early surgical debridement, as well as medical therapy with intravenous amphotericin followed by oral fluconazole. The literature related to candidal spinal infection is reviewed, and a rational approach to the management of this uncommon condition is proposed. A good outcome may generally be expected with early diagnosis as well as appropriate surgical and pharmacological treatment. Oral fluconazole appears to be useful in the management of candida spondylodiscitis complicated by epidural abscess formation. Treatment until a normal ESR is attained is ideal, and this may be as short as 3 months when surgical drainage has been adequately performed.     

Staphylococcus aureus in patients with rheumatoid arthritis under conventional and anti-tumor necrosis factor-alpha treatment

OBJECTIVE: To compare the prevalence of nasal and oral Staphylococcus aureus in patients with rheumatoid arthritis (RA) with the prevalence in controls with other rheumatic diseases, and to determine predictors of S. aureus carriage and the influence of treatment with anti-tumor necrosis factor-a (anti-TNF-alpha) agents. METHODS: Eighty-one patients with RA and 83 other control patients of 2 outpatient rheumatology clinics were cultured for nasal and oral carriage of S. aureus. Quantitative nasal cultures for S. aureus were performed from swabs of the anterior nares, the posterior pharynx, and the soft palate. Information on medications, medical conditions, and risk factors for S. aureus carriage was collected from all participants by a questionnaire and confirmed by chart review. RESULTS: The S. aureus carriage rate (nasal and/or oral colonization) was 34.6% among RA patients and 32.5% among controls (p = 0.87). Being treated with an anti-TNF-alpha agent plus methotrexate (MTX) was the only independent predictor of S. aureus carriage (OR 3.24, 95% CI 1.16-9.05, p = 0.025). The S. aureus carriage rate among RA patients treated with an anti-TNF-alpha agent plus MTX was 60% (9/15) versus 23.1% (3/13) in RA patients treated with an anti-TNF-alpha agent only (p = 0.049). All S. aureus isolates were susceptible to oxacillin. CONCLUSION: The S. aureus carriage rate among patients with RA was not higher than among controls. Treatment with anti-TNF-alpha agents was not associated with an increased S. aureus carriage rate. However, treatment with an anti-TNF-alpha agent plus MTX may predispose patients to S. aureus carriage.     

A case of candidal infection of gastric ulcers with characteristic endoscopic findings

While Candida infection is a common opportunistic infection, Candida-associated gastric lesions are far less frequent. We report a case of gastric ulcers due to candidal infection. A 73-year-old woman had ulcers refractory to treatment with a proton pump inhibitor (PPI) and Helicobacter pylori eradication. Endoscopic findings showed that this case involved 2 gastric ulcers with thick exudate mainly located in the fornix. Biopsy specimens from gastric ulcers revealed numerous Candida forms. The patient was treated with antifungal drugs and the ulcers healed completely on endoscopy. We should draw attention to our observation in elderly patients with gastric ulcers, and if we find gastric ulcers with such characteristic endoscopic findings, candidal infection of gastric ulcers should be considered.     

Esophageal Actinomycosis: A Case Report and Review of the Literature

Abstract A 37-year-old African–American male with acquired immunodeficiency syndrome (AIDS) presented with recurrent chest pain. An upper gastrointestinal endoscopy had been performed two months previously and esophageal biopsy revealed extensive candidal infection with ulceration. He temporarily responded to fluconazole. Repeat biopsy revealed actinomyces and continued candidal infection. Review of the original biopsy also demonstrated actinomyces in addition to candida. After initial response to therapy with penicillin, he worsened on outpatient therapy and subsequently expired from progression of disease. Lack of compliance may have been contributary. To date, 8 patients with esophageal actinomycosis have been reported, five of whom had AIDS. Of the remaining three, none was otherwise immunocompromised. This is the first report of esophageal actinomycosis occurring as a superinfection of candidal ulceration. We also describe the findings and utility of thoracic CT in this condition and review the literature.     

Candidal liver abscesses and cholecystitis in a 37-year-old patient without underlying malignancy

We report a case of candidal liver abscesses and concomitant candidal cholecystitis in a diabetic patient, in whom differences were noted relative to those found in patients with hematologic malignancies. In our case, the proposed entry route of infection is ascending retrograde from the biliary tract. Bile and aspirated pus culture repeatedly tested positive, and blood negative, for Candida albicans and Candida glabrata. Cholecystitis was cured by percutaneous gallbladder drainage and amphotericin B therapy. The liver abscesses were successfully treated by a cumulative dosage of 750 mg amphotericin B, We conclude that in cases involving less immunocompromised patients and those without candidemia, a lower dosage of amphotericin B may be adequate in treating candidal liver abscesses.     

Candidal vertebral osteomyelitis: report of 6 patients, and a review.

The incidence of deep-seated candidal infection is increasing, but candidal vertebral osteomyelitis is still rare. We describe 6 patients recently treated in our hospital. Conservative treatment failed in all. We reviewed the literature and identified 59 additional cases of candidal vertebral osteomyelitis. Candidemia was documented in 61.5% of them. The interval between the diagnosis of candidemia and the onset of symptoms of vertebral osteomyelitis varied widely, from days to >1 year. In patients without documented candidemia, there was a similar interval between the occurrence of risk factors for candidemia (present in 72% of the patients) and the onset of symptoms of vertebral osteomyelitis. Clinical, laboratory, and radiological findings are not specific for candidal spondylodiskitis. Final diagnosis is determined by means of culture of a biopsy specimen from the infected vertebra or disk. Treatment consisted of prolonged antifungal treatment, and it often included surgery. On the basis of our experience (for all 6 patients, initial conservative treatment with only antifungals failed), we recommend consideration of early surgical debridement in combination with prolonged antifungal therapy.     

Retinal lesions as clues to disseminated bacterial and candidal infections: frequency,natural history,and etiology

Invasive bacterial and candidal infections are known to involve the retina, but the natural history of the retinal lesions and the utility of ophthalmologic consultation in the critical care setting as a diagnostic tool are not well understood. We 1) performed weekly funduscopic examinations on 77 medical and surgical patients in intensive care units (ICUs), 2) analyzed results of serial ocular examinations in 180 non-neutropenic patients with candidemia, and 3) reviewed the English literature on the association of retinal lesions with disseminated bacterial or candidal infection (DBCI).We found that 15 (19%) of the ICU patients had retinal lesions consistent with DBCI. Of these 15, 1 had clearly sepsis-related retinal lesions, while 13 (87%) had 1 or more systemic disease that could have explained their retinal findings (6 diabetic retinopathy; 2 human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) retinopathy; 2 hypertensive retinopathy; 1 hemolytic uremic syndrome, and 1 leukemia). Multivariate analysis revealed that systemic disease (odds ratio 8.37, 95% confidence intervals: 3.24-21.56) independently correlated with the presence of retinal lesions while DBCI, trauma, hyperalimentation, and transfusion of blood products were not independently predictive in any analysis.Twenty of the 180 (15%) candidemic patients had retinal lesions. Two (1%) had classic 3-dimensional white lesions with vitreal extension, and 5 (2.7%) had chorioretinal lesions without vitreal haziness. Notably, 10% of patients had superficial retinal hemorrhages and/or cotton wool spots that could have been due to either candidemia or a systemic disease (diabetes, hypertension, renal failure, closed head trauma). Concurrent bacteremia occurred in 3 of the 27 patients with eye lesions. Retinal lesions resolved in a mean of 33 days. None of the patients had symptoms at the time of the retinal finding.We found 3 studies that prospectively assessed retinal lesions in bacteremic patients. The frequency of retinal lesions in these series varied from 12% to 26%, with the most common lesions being cotton wool spots followed by superficial retinal hemorrhages. White-centered hemorrhages were seen in about 15% +/- 2 of bacteremic patients. Five studies prospectively evaluated candidemic patients for Candida endophthalmitis. These studies observed rates from 0% to 78% for lesions consistent with candidal endophthalmitis. Most studies performed recently found that nonspecific lesions such as cotton wool spots or superficial retinal hemorrhages occurred with a frequency of 11% to 20%. The availability of less toxic antifungal agents, more frequent use of empirical therapy, and the trend to early treatment may be altering the frequency of this complication.Observation of a classic 3-dimensional retina-based vitreal inflammatory process is virtually diagnostic of endogenous endophthalmitis due to Candida spp., but such lesions are relatively uncommon. Conversely, nonspecific lesions that could be due to bacterial or candidal endophthalmitis (cotton wool spots, retinal hemorrhages, and Roth spots) are seen frequently. These lesions are most often due to an underlying systemic disease rather than an infection. Serial examinations provide the best evidence that a given lesion is due to an intercurrent infection. The current low rate of vitreal extension of retinal process appears to be due to the high rate of empirical or therapeutic use of antifungal agents in high-risk patient groups. Ophthalmoscopy should be performed in patients with known candidemia. However, ophthalmoscopic examination seems to have little value in assisting with the discovery of occult disseminated candidiasis or bacterial infection.     

Rate of carriage of Serratia marcescens in patients with and without evidence of infection.

The epidemiology of Serratia marcescens is poorly understood. We designed a study to investigate carriage sites of the organism, and possible modes of transmission of infection. Using Sorbitol-MacConkey agar with colistin 200 IU/ml and MacConkey agar with a 10 microg colistin disc we performed cultures from various sites in patients already infected with S. marcescens. Over the same period of time we also investigated all patients in the intensive care unit (ICU) for colonization with the agent. Environmental screening was performed in the ICU only. Of 37 infected patients, 65% demonstrated carriage at a second site and 43% at multiple sites. Throat carriage was found in 59%, faecal carriage in 42%, nasal carriage in 31% and urinary carriage in 22%. Carriage over several weeks was found in 22%. Of 40 ICU patients, 10% demonstrated nasal and/or throat carriage. Environmental screening yielded 4 isolates. All ICU patient strains and a strain from the ICU bedpan macerator were O14:K14 with similar random amplified polymorphic DNA types. These results show that patients with S. marcescens infection are likely to carry the organism at multiple sites and that carriage may be prolonged. A significant level of carriage was also found in non-infected patients in a unit where the organism was prevalent.     

Fluconazole in transplant recipients: options and limitations

Fluconazole is currently a first‐line agent used for therapy of non‐critically ill patients with candidal infection. Its efficacy, the availability of an oral formula, and its relatively low toxicity make it a very attractive drug for use in many clinical situations. The advisability of prophylaxis and empirical treatment in transplant patients is a difficult issue for the following reasons: the potential emergence of resistance to the azoles, the lack of solid data establishing its advantage over placebo and/or oral nonabsorbable antifungal agents in some of the clinical conditions encountered, its ineffectiveness against molds, and its cost. Judicious use of fluconazole where its efficacy has been well established would provide the best therapy for patients and would limit the emergence of potential pathogens. As new antifungal agents are approved for clinical use, appropriate clinical trials will need to be designed and conducted in order for clinicians to make rational decisions in selecting the most appropriate drug for the specific indication. Prophylaxis and treatment with fluconazole in various transplant situations is reviewed.     

Gallbladder and biliary tract candidiasis: nine cases and review

We review biliary tract and gallbladder candidiasis and define patient demographics, risk factors, prognostic factors, and treatment strategies for this infection. This is a 3-year retrospective review of our experience with this disease and a review of the English-language literature. Thirty-one cases of biliary tract and gallbladder candidiasis, including nine in our series, have been examined. The same risk factors that predispose patients to other forms of candidal infection are implicated here. No mortality was found with uncomplicated candidal cholecystitis in nonneutropenic patients treated with cholecystectomy alone. Patients with associated extrabiliary tract candidiasis or candidemia had worse outcomes and required both surgical intervention and antifungal therapy. When risk factors exist for the development of biliary tract or gallbladder candidiasis, the physician should be alert to this possibility. There is no need for antifungal therapy in cases of isolated candidiasis of the gallbladder in nonneutropenic patients.