Mervyn Shapiro

Multidrug-resistant Trichosporon asahii infection of nongranulocytopenic patients in three intensive care units.

ABSTRACT Trichosporon asahii (Trichosporon beigelii) infections are rare but have been associated with a wide spectrum of clinical manifestations, ranging from superficial involvement in immunocompetent individuals to severe systemic disease in immunocompromised patients. We report on the recent recovery ofT. asahii isolates with reduced susceptibility in vitro to amphotericin B (AMB), flucytosine, and azoles from six nongranulocytopenic patients who exhibited risk factors and who developed either superficial infections (four individuals) or invasive infections (two individuals) while in intensive care units. The latter two patients responded clinically and microbiologically to AMB treatment. All six isolates were closely related according to random amplified polymorphic DNA studies and showed 71% similarity by amplified fragment length polymorphism analysis, suggesting a common nosocomial origin. We also review the literature pertaining toT. asahii infections and discuss the salient characteristics of this fungus and recent taxonomic proposals for the genus.

A Multivariate Analysis of Risk Factors for Acquiring Bacteriuria in Patients With Indwelling Urinary Catheters for Longer Than 24 Hours

Data related to risk factors for catheter-acquired bacteriuria were collected prospectively on 112 patients consecutively catheterized for greater than 24 hours at the Hadassah University Hospital. Logistic regression analysis indicated that factors independently associated (p less than or equal to 0.05) with a higher risk of catheter-acquired bacteriuria were as follows: hospitalization in orthopedics or urology, ethnic origin (Arabs greater than Jews), insertion of a catheter after the sixth day of hospitalization, catheterization outside the operating theatres, lack of administration of systemic antibiotics, unsatisfactory catheter care, and prolonged duration (greater than or equal to 7 days) of catheterization before infection occurred. The risk associated with catheterization outside the operating theater could be explained by its correlate, that is, catheterization for incontinence/obstruction as opposed to output measurement. Life-table analyses demonstrated that the daily risk for acquiring bacteriuria during the first six days of catheterization was higher among patients ultimately catheterized for greater than or equal to 7 days than among those ultimately catheterized for less than 7 days (P less than 0.05).

INVASIVE PNEUMOCOCCAL INFECTIONS : A COMPARISON BETWEEN ADULTS AND CHILDREN

&NA; Abbreviations used in this article: CSF, cerebrospinal fluid; HIV, human immunodeficiency virus; IPI, invasive pneumococcal infections; MIC, minimal inhibitory concentration.

Deep Infection by Trichophyton rubrum in an Immunocompromised Patient

ABSTRACT Dermatophytes are common pathogens of skin but rarely cause invasive disease. We present a case of deep infection by Trichophyton rubrum in an immunocompromised patient. T. rubrum was identified by morphological characteristics and confirmed by PCR. Invasiveness was apparent by histopathology and immunohistochemistry. The patient was treated successfully with itraconazole.

Asymptomatic giardiasis in children.

Giardia lamblia infection was identified in 33 of 89 (37%) 3-month-old to 3-yr-old children who were followed with monthly stool examinations for up to 12 months in a day care center. The infection was mainly asymptomatic and usually associated with prolonged carriage of the parasite. There were no significant differences for height and weight achievements and mean hemoglobin values between Giardia-positive and Giardia-negative children. However, Giardia-positive children tended to achieve higher weight and height for age than Giardia-negative children; weight for age was above the 50th percentile in 69% of Giardia-positive vs. 40% of Giardia-negative children (alpha = 0.01). Giardia-positive children tended to have fewer symptoms related to the gastrointestinal and respiratory tracts as recorded by a weekly questionnaire. Lactase deficiency was detected by breath hydrogen testing in 8 of 26 Giardia-positive vs. only 1 of 21 Giardia-negative children (P less than 0.02). Healthy day care children with asymptomatic Giardia infection show no disadvantage and perhaps even an advantage in nutritional status and freedom from other illnesses.

Multidrug-Resistant Trichosporon asahii Isolates Are Susceptible to Voriconazole

We recently described the recovery of six clinical isolates of Trichosporon asahii from nongranulocytopenic patients that exhibited reduced susceptibilities to amphotericin B, flucytosine, ketoconazole, itraconazole, and fluconazole (7). In a recent paper Paphitou et al. reported (6) that the new investigational triazoles including voriconazole were highly potent against 24 isolates of Trichosporon asahii (MIC and minimal fungicidal concentration [MFC] of 0.25 and 0.5 mg/liter, respectively), confirming the prior observation that voriconazole has a lower MIC for T. asahii than do other azoles (4). Recently, the NCCLS has recommended testing yeasts for susceptibility to new triazoles including voriconazole (M27-A2) (5), and a commercial Etest kit for voriconazole has become available. Consequently, we performed susceptibility testing for our T. asahii multidrug-resistant isolates against voriconazole (7). The results (Table ​(Table1)1) strongly indicate that these six isolates, which exhibit reduced susceptibilities to fluconazole, are highly susceptible to voriconazole. The MICs and MFCs of voriconazole for these isolates are close (0.125 to 0.25 and 0.25 to 1.0 mg/liter, respectively), suggesting fungicidal activity of voriconazole. TABLE 1. Susceptibilities of T. asahii isolates to fluconazole and voriconazole Voriconazole is an expanded-spectrum synthetic triazole derivative of fluconazole. It inhibits the enzyme lanosterol 14-α-demethylase of Candida albicans and Aspergillus fumigatus with potencies 1.6 and 160 times greater, respectively, than those of fluconazole (3). Its potent fungicidal activity is likely due to the high affinity of voriconazole for fungal 14-α-demethylase, a concept supported by ultrastructural and biochemical analysis (1). However, unlike fluconazole, voriconazole also inhibits 24-methylene dihydrolanosterol demethylation of certain yeasts and filamentous fungi (3). These two reasons may explain why voriconazole may be effective in the treatment of mycoses like trichosporonosis that do not respond to other azoles. According to a new study, voriconazole is “superior” to amphotericin B for treating life-threatening invasive aspergillosis (2) and was recently approved in some European countries for the treatment of invasive aspergillosis. In our previous paper (7) we emphasized the importance of the patients basic immune status in determining the outcome of T. asahii infection. We concluded that in vitro resistance to antifungal drugs might not be critical in immunocompetent patients. However, immunocompromised patients may be dependent on fungicidal drug activity, so that infection with multidrug-resistant T. asahii isolates may be fatal in this population. Our new data with the low MICs and MFCs of voriconazole that confirm other in vitro studies suggest that voriconazole may offer a clinical solution in trichosporonosis when other antifungal drugs fail.

Iontophoresis–gentamicin delivery into the rabbit cornea, using a hydrogel delivery probe

PURPOSE To evaluate the efficacy of penetration of gentamicin into the cornea of rabbits using iontophoresis with a hydrogel-gentamicin containing probe. METHODS Eight of 10 groups (groups 3-10) of 6 rabbits (one eye per rabbit), underwent corneal iontophoresis using soft stable hydroxyethyl methacrylate hydrogel discs (80% water content) loaded with gentamicin sulphate which were mounted on an iontophoresis probe. The studied current intensities were 0, 0.1, 0.3 and 0.6 mAmp, and the durations of iontophoresis were 10 and 60 sec. Two control groups received 1.4% topical drops of gentamicin every 5 min for 1 hr (group 1) or sub-conjunctival injection of 10 mg gentamicin (group 2). Following sacrifice, aqueous humour was taken, corneas were excised, and gentamicin concentration was determined in aqueous humour and cornea samples. RESULTS Post-iontophoresis, the concentration of gentamicin in the corneas ranged from high (88.60 +/- 38.64 microg ml(-1)) to very low (0.10 +/- 0.89 microg ml(-1)). Both the control groups and those rabbits treated with current intensity of 0.1 mAmp or greater obtained therapeutic gentamicin levels in the corneas. Use of iontophoresis for 60 sec or current intensity greater than 0.1 mAmp obtained corneal gentamicin levels not different from sub-conjunctival injection. Application of current intensity of 0.1 mAmp or greater gave corneal gentamicin concentrations comparable to topical application of the drug, except when 0.6 mAmp were used for 60 sec (p = 0.05). Increasing current intensity or duration of iontophoresis significantly increased (p = 0.001 for both) gentamicin penetration into the cornea. Current intensity had more influence (Beta2 = 0.40) than duration (Beta2 = 0.13) on drug penetration. A significant interaction was found between the duration of iontophoresis and the current intensity. Very small or no concentrations of the drug were discovered in the anterior chambers of rabbits. CONCLUSIONS Iontophoresis using hydrogel-gentamicin probe may deliver therapeutic concentrations of gentamicin into the cornea.

Multivariate analysis of determinants of postoperative wound infection in orthopaedic patients.

In a prospective study of 376 orthopaedic patients, the relative contribution of host factors and patient-care variables to the risk of postoperative wound infection was evaluated. Host factors studied were age, sex, ethnic origin and diagnosis. The number of operations, the insertion of an open drain, the use of prophylactic antibiotics and the length of the operation were the patient-care variables studied. Of the risk factors identified, the performance of more than one operation during an admission had the highest risk coefficient, followed by the presence of an open drain, internal fixation of a fracture, and spine fusion. Within the group of operations for internal fixation, those for fractures of the femur had the highest risk of infection. In spine fusions those operations lasting 5 or more hours were associated with a high risk of infection. The length of stay of infected patients was on average 17.9 days longer than that of their individually-matched non-infected controls.

Severe infections in thalassaemic patients: prevalence and predisposing factors.

The incidence of infections among patients with thalassaemia and the role of risk factors for infection are uncertain. We studied the occurrence of infections necessitating hospitalisation in 92 homozygous β‐thalassaemia patients who had been followed longitudinally for decades, and investigated the role of potential risk factors for these infections. Pneumonia accounted for 26% of the infections and fever of unknown origin for 14%. Staphylococcus aureus was the major pathogen possibly related to injections associated with intensive chelation with deferoxamine. There was a significant increase in the rate of infection over time, notably after 15 years. Splenectomy correlated with the incidence of infection (P < 0·001) without being confounded by other variables and with highest frequencies of infections present after 10 years. A direct correlation between iron overload and infection was evident only before the initiation of iron‐chelating treatment (P < 0·01). Following initiation of deferoxamine, paradoxically, the infection rate increased (P = 0·046). The combination of splenectomy and deferoxamine treatment was associated with the highest adjusted infection rate. Parathyroid dysfunction and glucose‐6‐phosphate dehydrogenase deficiency were significantly associated with infection (P = 0·02 and P = 0·04 respectively). The infection rate in thalassaemia is affected mainly by the duration of the disease and is increased by splenectomy and, in the long term, by treatment with deferoxamine.

Invasive Group A Streptococcal Infections, Israel

We conducted a prospective, nationwide, population-based study of invasive group A streptococcal infections in Israel. We identified 409 patients (median age 27 years; range <1-92), for an annual incidence of 3.7/100,000 (11/100,000 in Jerusalem). The mortality rate was 5%. Bacteremia occurred in 125 cases (31%). The most common illnesses were soft-tissue infection (63%) and primary bacteremia (14%). Thirty percent of patients had no identifiable risk factors for infection. Eighty-seven percent of pharyngeal carriers had the same serotype as the index patient. M types included M3 (25%), M28 (10%), and M-nontypable (33%). A marked paucity of M1 serotype (1.2%) was detected. The results highlighted concentrated pockets of invasive disease in the Jewish orthodox community (annual incidence 16/100,000).