Cutaneous Granulomas: In Spain, Think of Leishmania

Martín-Ezquerra G, Fisa R, Riera C, et al. Role of Leishmania spp. infestation in nondiagnostic cutaneous granulomatous lesions: report of a series of patients from a western Mediterranean area. Br J Dermatol 2009; 161:320–5.

The finding of granulomas on microscopic examination of a skin biopsy not infrequently leads to an infectious diseases consultation, especially if the patient with the lesion has traveled. The list of potential etiologies, both infectious and noninfectious, of this finding is remarkably extensive [1]. The likely causes vary by geographic region and, when specific causes cannot be identified on histologic or classical microbiological examination, epidemiological and other exposure histories become critically important. Among the common etiologies of cutaneous granulomas in some areas of the world, even in the absence of classical ulcerative lesions, is Leishmania species.

In a study performed at hospitals in Barcelona and in Manacor, on the island of Majorca, Martín-Ezquerra and colleagues retrospectively examined skin biopsy specimens from 25 patients for whom the final diagnosis had been nonspecific granulomatous dermatitis. In each case, organisms could not be identified either histologically or by cultivation and no other definitive diagnosis was evident. A single skin lesion was present in 14 patients. Lesions were described as papules, plaques, or nodules and were present on the face in 10 patients, the trunk in 4, and the extremities in 11 and had been present for a mean duration of 7 months (range, 2 months to 2 years). Leishmania DNA was detected by real time PCR in 13 (52%) of cases. Immunohistochemical staining identified amastigotes in 7 of 20 specimens studied despite an inability to identify organisms with Giemsa stain. All 7 of these were PCR positive.

Leishmania infantum infection is prevalent in dogs in some regions of Spain and commonly causes visceral leishmaniasis in these animals. L. infantum infection is also frequent in humans in the Balearic Islands (Majorca, Formentera, Minorca), where 3.1% of blood donors have been found to be seropositive for this organism [2]. L. infantum DNA was detected in peripheral blood mononuclear cells by PCR in 5.9% of donors tested [2]. This organism is also the cause of human cutaneous leishmaniasis in Spain and also the causes visceral disease in HIV-infected patients there and in surrounding regions.

Thus, leishmaniasis must be considered in the differential diagnosis of skin lesions, whether papular, nodular, plaque-like, or ulcerative in residents of and travelers returning from the western Mediterranean region, as well as other areas of the world. Because the organism may not be detected in many cases by usual staining methods, more sensitive diagnostics must be applied. In this regard, the US Centers for Disease Control and Prevention performs culture for Leishmania, as well as PCR of tissue specimens from persons with suspected cases (for information on Leishmania testing, contact the Division of Parasitic Diseases at [770] 488-4475).

The etiologies of granulomatous dermatitis in many other geographic regions often have a very different distribution. An example comes from a study of 515 cases of infectious granulomatous dermatitis in India that found that 72.4% were manifestations of leprosy, 23.1% were associated with Mycobacterium tuberculosis infection, 3.3% were due to fungi or algae, and 1.2% were caused by post-kala azar leishmaniasis [3].

Wastewater Treatment and Antibiotic Resistance

Zhang Y, Marrs CF, Simon C, Xi C. Wastewater treatment contributes to selective increase of antibiotic resistance among Acinetobacter spp. Sci Total Environ 2009; 407:3702–6.

The high microbial density that occurs in the process of treatment of wastewater would appear to provide an ideal environment for the transfer of antibiotic resistance genes. Zhang and colleagues examined antibiotic resistance in one genus of gram-negative bacteria, Acinetobacter, before, during, and after wastewater treatment. Treatment of wastewater at the tertiary facility in Ann Arbor, Michigan, consisted of screening and grit removal, gravity sedimentation, biological nutrient removal and secondary sedimentation, sand filtration, and UV light disinfection. While treatment reduced the total bacterial population and that of Acinetobacter by ∼3 orders of magnitude, a comparison of isolates recovered at various stages found a significant increase in resistance to antibiotics as the wastewater progressed from raw influent to final effluent. Multidrug resistance was found in 33% of Acinetobacter species in the input material and in 72.4% of the final product.

Antibiotic-resistant bacteria can be found in a wide variety of environments, including soil and water, and antibiotics can be found in some of these same environments, in some instances in remarkably high concentrations. Studies in India in an area near major pharmaceutical production facilities, for example, found ciprofloxacin concentrations of >1 µg/mL in water from several village wells, up to 6.5 µg/mL in nearby lakes, and as high as 14 µg/mL in the effluent of a wastewater treatment plant [1]. These concentrations are sufficient to exert a significant selective pressure on the bacterial ecology, potentially leading to the emergence of antibiotic-resistant strains. The stresses exerted in the wastewater treatment process may potentially lead to emergence of resistance. A wide variety of antibiotic resistance genes have been identified in wastewater treatment effluents, including the mecA gene, and the conditions of high microbial density that result during the treatment process could potentiate the horizontal transfer of these genes. It should be noted that reclaimed wastewater is being increasingly used for agricultural irrigation and water of public parks, but evidence indicates that, if standards for the water, such as those of the World Health Organization, are maintained, the practice is safe [2]. Nonetheless, wastewater treatment may have the potential to contribute to the growing problem of antibiotic resistance.

Silent Seizures in Critically Ill Patients with Sepsis

Oddo M, Carrera E, Claassen J, et al. Continuous electroencephalography in the medical intensive care unit. Crit Care Med 2009; 37:2051–6.

Oddo and colleagues retrospectively evaluated the results of continuous electroencephalographic (cEEG) monitoring for at least 12 h of critical care patients without known acute neurological injury, 60% of whom had sepsis as their primary diagnosis. Monitoring was most often performed because of suspected clinical seizures or unexplained changes in level of consciousness. The median time from intensive care unit (ICU) admission to initiation of monitoring was 1 day; 91% of subjects were undergoing mechanical ventilation, and 48% were comatose. Electrographic seizures (ESs) were observed in 21 (10%) of the 201 consecutive patients examined, whereas periodic epileptiform discharges (PEDs) were observed in 34 (17%); both were present in 10 (5%). Overall, 45 (22%) of patients had at least 1 of these findings. Only 33% of patients with these EEG abnormalities had observed physical seizures.

Among patients with sepsis, 32% had ES and/or PED, compared with only 9% without sepsis (P<.001) and sepsis at the time of ICU admission was the only significant predictor of these EEG abnormalities on multivariate analysis (odds ratio, 4.6; 95% confidence interval, 1.9–12.7). The presence of ES and/or PED were associated with poor outcomes, as was the occurrence of convulsive seizures.

Encephalopathy is a frequent occurrence in patients with severe sepsis and often has a multifactorial etiology [1]. This study suggests that many such patients may have abnormal brain electrical activity, including evidence of electrical seizures, often without observed convulsive activity. Although the presence of ES is generally accepted as having clinical significance, the significance of PEDs has remained uncertain. PEDs, nonetheless, are evidence of abnormal brain activity reflective of recurrent depolarizations. Although this study has significant limitations, including its retrospective nature, the stated selection bias, and the lack of complete information regarding underlying disease and therapies which might have affected the findings, the remarkable frequency of the observed EEG abnormalities demands that the issue be addressed by prospective clinical studies. An important aim of such studies must be to examine the question of whether these findings simply represent markers of severe illness or whether they contribute to unfavorable outcomes and whether prophylactic and/or therapeutic intervention is beneficial.