Successful use of azithromycin for Escherichia coli-associated renal allograft malakoplakia: a report of two cases.

Malakoplakia is a chronic granulomatous disease associated with incomplete clearance of bacterial pathogens. A multimodal approach to therapy includes antimicrobials with intracellular activity, reduction in immunosuppression, and debulking of lesions. Azithromycin has an intracellular mechanism of action and enhanced Gram-negative activity compared to other macrolides. Despite some in vitro data to support its use, there are no clinical breakpoints or epidemiological cut-off values for most Enterobacterales from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) or the Clinical and Laboratory Standards Institute (CLSI). We present two cases, previously unreported, of Escherichia coli associated renal allograft malakoplakia successfully treated with azithromycin.

Pulmonary malacoplakia at early stage: use of polymerase chain reaction for detection of Rhodococcus equi.

Malacoplakia is a rare inflammatory condition characterized by the accumulation of benign macrophages associated with pathognomonic Michaelis-Gutmann bodies (MGBs). It is usually found in the genito-urinary tract, and has been associated with immunocompromised states. In this short report, we present 5 patients with pulmonary nodules clinically suspicious for primary or metastatic lung cancer. The histologic examination of the surgical specimens revealed a nonspecific granulomatous chronic disease, and despite the paucity of classical MGBs, a pulmonary malacoplakia was suspected. In all cases the opportunistic pathogen Rhodococcus equi (R. equi) was identified by 16S rRNA gene sequence analysis, leading to the final pathological diagnosis of malacoplakia. We conclude that pulmonary malacoplakia associated with R. equi is a rare disease affecting also immunocompetent patients. The pathogenesis and the diagnostic problems are discussed. Since infection by R. equi is treatable, the importance of its early recognition should be emphasized.

Ultrastructural evidence of the evolutional process in malakoplakia.

CONTEXT: Malakoplakia can be caused by incomplete digestion of Escherichia coli by lysosomes, leading to recurrent urinary tract infections and consequential mass-forming events that mimic tumors. OBJECTIVES: By using ultrastructural findings, we aimed to specify the process of phagolysosome to evoke malakoplakia. DESIGN: We observed a series of processes to form a peculiar Michaelis-Gutmann (MG) body in three patients with malakoplakia and compared with xanthogranulomatous pyelonephritis. RESULTS: The ultrastructural findings were realigned according to the sequence of events as pre-phagosomal, phagosomal, and post-phagosomal stages. For the mature MG body, numerous lysosomal aggregates targeting pathogens and subsequent incomplete digestion are prerequisite factors for the pre-phagosomal stage. Scattered lamellated residue is late evidence of the pre-phagosomal stage. Phagosomes can be formed by the fusion of multiple pathogens and multiple lysosomes. We utilized transmission and scanning electron microscopy to speculate on the process of phagolysosomal formation. CONCLUSION: The recognition of E. coli captured by phagosomes or partially damaged by lysosomal attack within the cell was recorded for the first time. Furthermore, SEM observation was performed on human tissue.

Cutaneous malakoplakia in an HIV-positive patient.

Malakoplakia is an uncommon granulomatous infectious disease that is found primarily in the genitourinary tract, but may rarely involve the skin. We report a case of cutaneous malakoplakia in an HIV-positive patient diagnosed on the basis of Michaelis-Gutman bodies. The patient presented with ulcers, draining sinuses and tender papules and nodules mainly on perigenital area, buttocks and right thigh.

Ultrasonographic evaluation of renal infections.

Renal sonography can be easily performed and provides valuable information concerning the underlying disease process, helping to decide appropriate management. This article reviews the important renal infections, such as pyelonephritis, emphysematous pyelonephritis, renal abscess, hydatid disease, renal tuberculosis, pyonephrosis, and HIV-associated nephropathy.

Malacoplakia. Two case reports and a comparison of treatment modalities based on a literature review.

Malacoplakia is a rare infectious disease that has been almost exclusi vely reported in urology and pathology journals. We studied two cases of malacoplakia that were primarily referred to the department of internal medicine because of fever and abdominal masses. In one patient, malacoplakia was diagnosed in the unusual ovarian location, while in the other patient a large renal mass was found and ciprofloxacin therapy failed because of bacterial resistance. The clinical and radiologic appearance of malacoplakia often mimics that of a malignant tumor. The principal disorder is probably a monocytic-macrophagic bactericidal defect. A definitive diagnosis depends on microscopic detection of Michaelis-Gutmann bodies by means of von Kossa stain. We outlined treatment strategies on the basis of a review of the literature since 1981, which included 140 cases. If possible, immunosuppressive drugs should be stopped. Quinolone antibiotic treatment and surgical excision or incision and drainage lead to the highest cure rates (90% and 81%, respectively). Specific intracellular penetration of quinolone antibiotics is a possible reason for the higher cure rate achieved with these antibiotics. Bethanechol has been suggested to correct the supposed fundamental disturbance by increasing the intrecellular cyclic guanosine monophosphate concentration, but there is still no convincing evidence of its clinical efficacy.

[Malakoplakia of the submandibular gland in a renal transplant patient]. / Malakoplakie de la glande sous-mandibulaire chez un patient transplanté rénal.

INTRODUCTION: Malakoplakia (MP) is a rare granulomatous disease, usually occurring in immunocompromised patients, linked to Escherichia coli infection. The lesions are usually located in the genitourinary tract, but there is a great variability in the topography and the clinical presentation. CASE REPORT: A 70-year-old diabetic kidney transplant patient under immunosuppressive treatment presented with a voluminous submandibular chronic lesion, involving the skin, associated with a burgeoning lesion of the oral mucosa. Histological examination of biopsies concluded to MP and bacteriological samples were positive for E. coli. Antibiotic treatment allowed for the regression of the lesion before surgical removal. Histological examination of resected material confirmed the diagnosis of invasive MP of the submandibular gland. DISCUSSION: The diagnosis of MP relies on histological examination, showing the presence of von Hansemann's cells and Michaelis- Gutmann bodies. The treatment is based on active antibiotics targeted against intracellular bacteria, possibly associated with surgery. We report the first case of MP involving the submandibular gland.

Malakoplakia mimicking carcinoma metastatic to lung.

Malakoplakia is a rare inflammatory disorder which infrequently involves sites outside of the lower genitourinary or gastrointestinal tract. We report a case of malakoplakia in which the patient presented with a left renal mass and bilateral pulmonary nodules suggestive of metastatic renal carcinoma. Postmortem cultures of the lesions grew E. coli; macrophages at both sites contained gram-negative bacilli and numerous Michaelis-Gutmann bodies. X-ray spectroscopic analysis of the bodies showed wide variation in calcium, phosphorus, and iron content, suggesting that Michaelis-Gutmann bodies were formed in part by the deposition of amorphous salts.

Pulmonary malacoplakia associated with Rhodococcus equi infection in a patient with AIDS.

An AIDS patient with a cavitary lung lesion was found to have pulmonary malacoplakia associated with Rhodococcus equi infection. The diagnosis was based on the typical histologic features of transbronchial biopsy and a positive bacterial culture. All 13 reported cases of AIDS patients with pulmonary malacoplakia were associated with R equi. The recognition of this unique entity is important because of its responsiveness to therapy.

Malakoplakia of palatine tonsil.

This paper's purpose is to document a case of unilateral tonsillar malakoplakia. Escherichia coli was repeatedly cultured from the lesion, and the isolate was studied by expert microbiologists who found no abnormalities in its biologic properties. The course of the lesion was followed by repeated punch biopsies before, and after the institution of antibiotic therapy. Following treatment, healing was characterized histologically by the disappearance of edema, granulocytes and bacilli, a striking initial increase in the number of Michaelis-Gutmann (MG) bodies and other calcified particles, and an increase in the number of foamy plasma cells, before the eventual resolution of the lesion.

Intracellular Escherichia coli in urinary malakoplakia: a reservoir of infection and its therapeutic implications.

Urinary malakoplakia may pursue an aggressive clinical course with persistent infection, despite seemingly appropriate antibiotic therapy. The authors studied seven adult females with urinary malakoplakia. Specific immunocytochemical staining demonstrated intracellular Escherichia coli in malakoplakia tissue in four patients. In two of the four patients, the bacteria were present despite antibiotic-induced sterile urines at time of biopsy. Cessation of therapy consistently lead to recurrent bacteriuria in these patients. In one such patient, the intracellular bacilli were confirmed as E. coli by culture of crushed malakoplakia tissue and electron microscopic study; the organisms were a routine E. coli strain susceptible to multiple previously administered antibiotics. Only sequential treatment with bethanechol chloride and trimethoprim-sulfamethoxazole, however, eliminated the infection; all three drugs are thought to be capable of enhancing intracellular killing of bacteria. Conventional antibiotic therapy failed to halt progression of disease in other malakoplakia patients. The data indicate that intracellular bacteria may serve as a reservoir of persistent/recurrent infection in urinary malakoplakia. Optimal therapy should include therapeutic agents that may control intracellular organisms.

Clinical and laboratory studies into the pathogenesis of malacoplakia.

Three cases of malacoplakia are described. Electron microscopic studies revealed intact bacteria or bacteria in varying states of degradation within phagolysosomes of the malacoplakic macrophages. Michaelis-Gutmann bodies arise within the phagolysosomes. These findings suggest that the bacteria incorporated within the phagolysosomes persist as dense amorphous aggregates which later become encrusted with calcium phosphate crystals to form the laminated Michaelis-Gutmann bodies. Possible explanations for the unusual macrophage response in malacoplakia are: (1) infection with an unusual strain of bacteria, (2) an immunological abnormality affecting intracellular killing of organisms, and (3) an abnormality affecting intracellular digestion of organisms. In considering each of the possibilities, we have been unable to detect any unusual strain of infecting organisms in association with malacoplakia, and in vitro studies have revealed normal T lymphocyte response to mitogen and normal monocyte bactericidal capacity. According to the history, each patient had reason to have a compromised immune status; in only one, however, was this demonstrated.

Malacoplakia of epididymis.

Malacoplakia localized to the epididymis is described. Ultrastructural study revealed the presence of bacterial bodies in phagolysosomes of malacoplakic macrophages. The possible role of the phagocytosed bacteria in the pathogenesis of malacoplakia is briefly discussed.

Malakoplakia and tuberculosis.

A 33 year old woman developed a soft mass in the left anterior neck following treatment for pulmonary tuberculosis. An incisional biopsy was performed and a cold abscess drained. Histology confirmed a diagnosis of tuberculosis. In addition, there were numerous intracellular bodies which resembled the Michaelis-Gutmann bodies of malakoplakia. This case however displayed some atypical histological, histochemical and ultrastructural features, which are highlighted in this report. The mass responded to combination antituberculous treatment.

Malakoplakia of the neck.

Malakoplakia that presents in the head and neck is very rare. We describe a 76-year-old man who presented with an inflammatory mass in the lateral aspect of the neck that clinically mimicked a tumoral expansion and was consistent with a cervical malakoplakia. To our knowledge, this is the second case reported with manifestations of this chronic inflammatory disease localized in the neck. Malakoplakia is a rare granulomatous disease that most frequently involves the genitourinary tract and occurs in an immunodeficient host. The symptoms are nonspecific and the diagnosis is based on the histologic findings. In the present case, the biopsy specimen of the cervical mass revealed a collection of numerous von Hansemann cells containing Michaelis-Gutmann bodies, which are pathognomonic of malakoplakia. Bacteriologic analysis identified Escherichia coli. The evolution was favorable after surgical excision and prolonged antibiotic therapy with fluoroquinolones.

Detection of the 20-kDa virulence-associated antigen of Rhodococcus equi in malakoplakia-like lesion in pleural tissue obtained from an AIDS patient.

A malakoplakia-like lesion was detected in a pleural biopsy from an AIDS patient presenting clinical and radiologic features of pneumonia. Cultures of bronchoalveolar lavage and pleural fluid evidenced Rhodococcus equi as the causative agent of pleuro-pulmonary infection. Immunochemical characterization of the R. equi isolate showed the presence of a strain similar to the ATCC 33704 reference strain presenting the capsular antigen of serotype 4, and the intermediate virulence-associated antigen of 20-kDa. Histopathology of the patient's pleural biopsy showed plaques of macrophages interspersed with lymphocytes, and intracytoplasmic cocci and bacilli in macrophages, which were variably acid-fast positive. Immunohistochemistry of cocci, bacilli and their degradation products resulted strongly positive when stained with a mouse monoclonal antibody (MAb) produced against the 20-kDa antigen. This finding could have important implications for the pathogenicity of R. equi for human beings, since we do not know yet all the factors involved in the formation of malakoplakia. Indeed, the results obtained in the present study, taken together with the results obtained for pigs inoculated with R. equi strains of intermediate virulence (Madarame et al. 1998), raise the possibility that most strains presenting the 20-kDa antigen may be capable of inducing malakoplakia. If this hypothesis is confirmed by immunohistochemical analysis of human pulmonary malakoplakia cases due to R. equi, the detection of this antigen may be extremely helpful in the diagnosis and treatment of such patients. This is the first report of R. equi infection in human beings that suggests a relationship between pleural malakoplakia and the virulence-associated antigen of 20-kDa.

Cerebral malakoplakia associated with neonatal herpes virus infection.

Cerebral malakoplakia has been recognized as a complication of probable neonatal herpes encephalitis and may be associated with persistent neurologic deficits including seizures. At autopsy, an eight-month-old boy had a discrete cystic gliotic lesion in his left inferior frontal lobe with malakoplakia. Perinatal herpetic cutaneous lesions were seen and were successfully treated with medication at two weeks of age. Subsequent discontinuation of his anti-epileptic drugs was followed by sudden unexpected death. Immunohistochemical stains and electron microscopy of his brain failed to reveal herpes simplex virus.