Drug Of Choice For Therapy Research Articles

Bedaquiline practice in treatment of extensively drug-resistant mycobacterium tuberculosis in children: Clinical cases

Background. Bedaquiline is currently a drug of choice in therapy for extensively and multidrug-resistant tuberculosis. It is indicated for children from a 6-year age and young adults as part of a combination chemotherapy, in compliance with the medical council’s (MC) regulation on active extensively and multidrug-resistant tuberculosis.Clinical Cases Description. The article describes the clinical cases of bedaquiline treatment of extensively drug-resistant tuberculosis in сhildren. Patient B., 16 yo, was routinely admitted to a children’s ward of the Orenburg Regional Clinical Antituberculosis Dispensary with the preliminary diagnosis: exudative pleurisy-complicated S1,2 infiltrative focal tuberculosis of left lung. Mycobactérium tuberculósis (MBT) (-). Complaints of cough, painful chest at deep breath, 37.3°C-elevated body temperature. Chest X-ray: left focal shadows in S1,2, intensive homogeneous darkening due to pleural effusion from diaphragm to anterior segment of rib III. An urgent pleural puncture was performed to sample fluid for MBTculture and PCR resistance tests to streptomycin and rifampicin. The patient was treated with anti-tuberculosis drugs according to the IV chemotherapy regimen. Taking into account the MBTculture results, the Medical Board took the decision to start using the V chemotherapy regimen with the inclusion of up to 180 doses of bedaquiline. The patient received anti-TB drugs according to chemotherapy regimen IV. Based on the pleural fluid PCR tests, the MC prescribed a conversion to chemotherapy regimen V with adding bedaquiline up to 180 doses. After 7 months of positive dynamics, the patient was transferred to continuation phase at a children’s sanatorium. Patient S., 10 yo, was routinely admitted to a children’s ward of the Orenburg Regional Clinical Antituberculosis Dispensary with the diagnosis: two-sided bronchopulmonary intrathoracic lymph nodes tuberculosis (ILNTB), calcification phase, MBT (-), follow-up care level I. Given the child’s triple contact with tuberculosis carriers, including extensively drug-resistant (XDR) tuberculosis, the MC prescribed antibacterial drug chemotherapy IF regimen V with adding bedaquiline up to 180 doses: pyrazinamide (Z), prothionamide (Pto), para-aminosalicylic acid (PAS), cycloserine (Cs), bedaquiline (Bq) concurrently with vitamins and hepatoprotectors (ZPtoPASCsBq). After 4 months of positive dynamics, the patient was transferred to anti-bacterial therapy continuation phase 4 (ZPtoCsPAS) for up to 12 months at a children’s sanatorium.Conclusion. The clinical cases presented demonstrate the efficacy of bedaquiline in adolescents having extensively drug-resistant focal pulmonary tuberculosis and intrathoracic lymph nodes tuberculosis. The prescription of bedaquiline in this age cohort requires careful justification and a monitoring of adverse reactions and antituberculosis chemotherapy complications.

Strongyloidiasis in clinical practice: challenges in diagnostics and treatment (brief review and clinical observations)

High priority of soil-transmitted helminths worldwide and in the Russian Federation is due to their vast distribution and the severe pathological features they induce in humans. Recently, it was observed that awareness of clinicians regarding this disease category was markedly decreased, although no significant decline of the disease occurrence has been recorded, whereas rate of imported cases of parasitic diseases including soil-transmitted helminths like strongyloidiasis mainly originating from subtropical or tropical countries rose in non-endemic regions. Lack of alertness on diseases like strongyloidiasis impedes timely diagnostics and treatment. Global prevalence of strongyloidiasis was estimated to range within 30—100 million people, however the World Health Organization (WHO) suggests that it was underestimated as precise data in endemic countries remain unknown. The occurrence of these helminths has been recorded in regions of temperate-continental climate: Western Ukraine, Belarus, Moldova, the Caucasus, Central Asia, as well as in Eastern Europe and the Mediterranean region. In the Russian Federation locally acquired infections are frequently recorded in the Krasnodar Territory and Rostov Region. Here, based on multi-year experience in management of patients with strongyloidiasis we present our data and brief review of publications and systematic literature related to the challenges of its clinical picture, diagnostics and treatment. Life cycle, basic biological parameters of free-living helminth in nature and distinctive features of autoinfection related to strongyloidiasis were reviewed. Special attention was paid to the risk of developing severe forms (hyperinfection and disseminated strongyloidiasis) especially in immunocompromised hosts: HIV infection, radiotherapy followed by chemotherapy, long-term corticosteroid use. Difficulties in diagnosing Strongy-loides stercoralis infection are due to its polymorphic and non-specific clinical manifestations, as well as the lack of clinical knowledge and awareness about the disease. Clinical importance of parasitological methods for larvae detection was underlined. It was noted that the drug of choice in therapy of strongyloidiasis is ivermectin unapproved yet in Russia, whereas albendazole as an alternative drug exerts poorer efficacy, justifying a need to repeat treatment courses to establish full recovery from the disease.

Pneumocystis jiroveci.

Pneumocystis jiroveci remains an important fungal pathogen in a broad range of immunocompromised hosts. The natural reservoir of infection remains unknown. Pneumocystis jiroveci Pneumonia (PJP) develops via airborne transmission or reactivation of inadequately treated infection. Nosocomial clusters of infection have been described among immunocompromised hosts. Subclinical infection or colonization may occur. Pneumocystis pneumonia occurs most often within 6 months of organ transplantation and with intensified or prolonged immunosuppression, notably with corticosteroids. Infection is also common during neutropenia and low-lymphocyte counts, with hypogammaglobulinemia, and following cytomegalovirus (CMV) infection. The clinical presentation generally includes fever, dyspnea with hypoxemia, and nonproductive cough. Chest radiographic patterns are best visualized by computed tomography (CT) scan with diffuse interstitial processes. Laboratory examination reveals hypoxemia, elevated serum lactic dehydrogenase levels, and elevated serum (1→3) β-D-glucan assays. Specific diagnosis is achieved using respiratory specimens with direct immunofluorescent staining; invasive procedures may be required and are important to avoid unnecessary therapies. Quantitative nucleic acid amplification is a useful adjunct to diagnosis but may be overly sensitive. Trimethoprim-sulfamethoxazole (TMP-SMX) remains the drug of choice for therapy; drug allergy should be documented before resorting to alternative therapies. Adjunctive corticosteroids may be useful early in the clinical course; aggressive reductions in immunosuppression may provoke immune reconstitution syndromes. Pneumocystis pneumonia (PJP) prophylaxis is recommended and effective for immunocompromised individuals in the most commonly affected risk groups.

The use of multiplex-PCR method in identification of Candida species from vaginal candidiasis patients

Abstract. Susilawati, Rahadiyanto KY, Ramdja, Theodorus, Hermansyah. 2019. The use of multiplex-PCR method in identification of Candida species from vaginal candidiasis patients. Biodiversitas 20: 3063-3069. Vaginal Candidiasis is an infection caused by a yeast called Candida which may be resulted in different virulences, thus leading to a varied drug of choice for therapy. The objective of this study was to determine the sensitivity and specificity of multiplex-PCR test in detecting Candida species in women with clinical diagnosis of vaginal candidiasis. There were 79 vaginal swab samples which fulfill inclusion criteria. Samples were cultured at ASD media for isolation of Candida spp. Identification of Candida spp. was conducted using both biochemical fermentation and multiplex-PCR methods. Primers pairs used in multiplex-PCR were universal primer ITS1 and ITS2, and specific primer CA3 and CA4. The identification test of multiplex-PCR resulted in Candida krusei: sensitivity: 100%, specificity:61,1%, Positive Prediction Value (PPV):63.2%, Negative Prediction Value (NPV): 100%; C. glabrata: sensitivity:0%, specificity: 100% PPV: 0% NPV: 76.7%; C. tropicalis: sensitivity:100%, spesificity:100%, PPV: 100% NPV: 100%; C. albicans: sensitivity: 33.3%, specificity: 100%, PPV: 100%, NPV: 93.1% and C. stellatoidea: sensitivity:: 100%, specificity:92.6%, PPV: 60%, NPV: 100%. These results suggested that multiplex-PCR method becomes a rapid alternative in identifying species of Candida due to its high sensitivity and high specificity.

Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Pneumocystis jiroveci fungal infection transplant recipients. Pneumonia (PJP) may develop via airborne transmission or reactivation of prior infection. Nosocomial clusters of infection have been described among transplant recipients. PJP should not occur during prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX). Without prophylaxis, PJP risk is greatest in the first 6months after organ transplantation but may develop later. Risk factors include low lymphocyte counts, cytomegalovirus infection (CMV), hypogammaglobulinemia, treated graft rejection or corticosteroids, and advancing patient age (>65). Presentation typically includes fever, dyspnea with hypoxemia, and cough. Chest radiographic patterns generally reveal diffuse interstitial processes best seen by CT scans. Patients generally have PO2 <60mmHg, elevated serum lactic dehydrogenase (LDH), and elevated serum (1→3) β-d-glucan assay. Specific diagnosis uses respiratory specimens with direct immunofluorescent staining; invasive procedures may be required. Quantitative PCR is a useful adjunct to diagnosis. TMP-SMX is the drug of choice for therapy; drug allergy should be documented before resorting to alternative therapies. Adjunctive corticosteroids may be useful early. Routine PJP prophylaxis is recommended for at least 6-12months post-transplant, preferably with TMP-SMX.

Reappraisal of glossopharyngeal neuralgia

Abstract Glossopharyngeal neuralgia is a rare disease characterized by severe paroxysmal attacks of pain in the distribution of the 9th cranial nerve. Glossopharyngeal neuralgia primarily can be caused by compression of the glossopharyngeal nerve, but in some cases, no cause is evident. Carbamazepine is the current drug of choice in therapy, but modern neurosurgical treatment will probably become more common in the future. Autonomic disturbances may occur during pain attacks in some patients. We describe a 42-year old Saudi male suffering from glossopharyngeal neuralgia with transitory unconsciousness due to cardiac asystole and arterial hypotension accompanying the attack of pain. We review pathogenesis, diagnosis, treatment and prognosis.

Disseminated paracoccidioidomycosis prediagnosticated as neoplasm: An important challenge in diagnosis using rt-PCR

This paper presents a case of disseminated paracoccidioidomycosis in a 62-year-old male patient, who lives in Belo Horizonte, MG, Brazil. The patient was hospitalized with icteric syndrome of cholestatic pattern and weight loss, with loss 30kg in 5 months. The imaging of the abdomen showed lesion of infiltrative pattern, affecting gallbladder and intrahepatic bile ducts, suggesting neoplasia of malignant behavior, besides to presenting the yellow nail syndrome. Dermatological examination presented erythematous-infiltrated plaques in the occipital region. Also, the patient presented tegumentary lesions on the scalp and lumbar region from which the histopathological examination was carried out, which evidenced yeasts cells. The drug of choice for therapy was Liposomal Amphotericin-B. At the end of the antifungal treatment, liver enzyme dosages were normalized and there was improvement of the general condition of the patient, as well as the skin lesions. Here, we demonstrate the importance of molecular biology to confirm the diagnosis. Especially in cases of difficult diagnosis.

Pharmacodynamics and Pharmacokinetics of Antifungals for Treatment of Invasive Aspergillosis

Amphotericin B has been the only therapeutic option for invasive aspergillosis over decades. It acts by binding to membrane ergosterol, lipid peroxidation and proton-ATPase inhibition. Amphotericin B is eliminated unchanged via urine and feces. It displays a considerable toxicity, particularly infusion-related adverse events and renal damage. Continuous infusion and administration of lipidformulations of amphotericin B are strategies to improve its tolerability. Amphotericin B has a post-antifungal effect (PAFE), and its peak concentration is probably crucial for its fungicidal efficacy. The amphotericin B lipid-formulations display largely different pharmacokinetics. Kinetics of amphotericin B which is liberated from its lipid encapsulation in the plasma is similar for all three available lipid formulations. Azoles inhibit the synthesis of fungal cell membrane ergosterol. The triazoles itraconazole, voriconazole and posaconazole are active against Aspergilli. Voriconazole is the drug of choice for therapy of invasive aspergillosis. It is metabolized in the liver and metabolites are excreted via the kidneys. Posaconazole is licensed for antifungal prophylaxis in hematological high-risk patients and for salvage therapy of invasive aspergillosis. A variety of drug-drug interactions have to be considered with all azoles. The ratio between the area under the time-concentration profile (AUC) and the minimal inhibitory concentration (MIC) is the relevant pharmacokinetic/ pharmacodynamic parameter for azoles. Caspofungin the only echinocandin licensed for second line therapy of invasive aspergillosis is fungistatic to Aspergilli displaying a paradoxical pharmacodynamic effect. Caspofungin elimination is independent from renal function. Although it is metabolized in the liver its potential for drug interactions is moderate.

Fatal pneumocystis jiroveci pneumonia in ABVD-treated Hodgkin lymphoma patients

Dear Editor, Lung infections are serious complications in patients with hematological malignancies [1–4]. Pneumocystis jiroveci is an important causative organism. T cell deficiency and preceding corticosteroid therapy are important risk factors for Pneumocystis jiroveci pneumonia (PCP). The course of PCP may be fulminant and in patients who require mechanical ventilation, the prognosis is poor. When PCP was identified as one of the most important severe infections in children aggressively treated for acute lymphoblastic leukemia in the 1970s, cotrimoxazole was introduced as the drug of choice for therapy as well as for prophylaxis [5]. However, the precise degree of immunosuppression at which PCP may occur is still not fully elucidated. Thus, we are still not able to identify patients who would benefit from prophylaxis with a satisfactory accuracy [1, 3, 6]. We identified several patients with severe PCP belonging to patient categories not generally recommended to be treated with prophylactic cotrimoxazole. Based on this observation, we decided to investigate PCP among a spectrum of patients with hematological malignancies at our center during an 8-year period. The main objective was to further characterize patients who would have benefited from prophylaxis. At the Department of Hematology, Karolinska University Hospital Solna, all categories of hematological malignancies/ disorders are treated. Patients with new or increasing pulmonary infiltrates are usually examined by both thoracic computerized tomography and bronchoscopy with extensive sampling for possible causative microbial pathogens. Bronchoscopy is avoided in patients who are considered not to tolerate this procedure due to comorbidity, hypoxemia or severe thrombocytopenia. All results from P.jiroveci testing during the years 1999– 2006 were retrospectively retrieved from the Swedish Institute for Infectious Disease Control. The specimens have been examined by immunofluorescence (IFL) by use of monocolonal antibodies [7]. Patients with a positive result by IFL treated at our center were identified and their clinical charts reviewed. The study was approved by the local ethics committee. P.jiroveci was identified by IFL on bronchoscopically obtained secretions in 31 patients, and by IFL on sputum or nasopharyngeal secretions in nine and one patient, respectively. All patients had abnormal findings on chest X-ray (36/38) or CT (26/26). A total of 41 patients (40 with a hematological malignancy and one with a severe autoimmune hemolytic anemia) with PCP were identified during the 8 year-period. Their median age was 62 years (range 23-83 years; Table 1). None of the patients had received PCP prophylaxis. The large majority of patients (95%) had a lymphoproliferative malignancy (Table 1). Twenty-three patients (56%) had progressive disease and four of the eight Hodgkin lymphoma patients, including one patient with a concomitant myeloma, succumbed to PCP. M. Kalin Department of Medicine, Division of Infectious Diseases, Karolinska University Hospital Solna and Institutet, Stockholm, Sweden

Rickettsial tick bite fever: clinical aspects and laboratory diagnosis 1

During the last decades of the past century the frequency of rickettsial tick-bite fever has extremely increased. Patients often do not feel or realize a tick-bite. The most important diagnostic criterion after a tick-bite is a blue-red, later black skin ulcer with a black rim, called eschar or tache noir, and local lymph adenopathy. Clinical diagnosis can already be based on these symptoms. In some cases, the typical dark skin discoloration is absent or the color change may be misinterpreted as a minor skin injury. Also, exanthems occur and are of a maculo-papulous appearance. They show different variations and are often absent. In serological diagnosis, nearly half of the patients show antibodies against rickettsiae. Doxycycline as the drug of choice for therapy with one-day treatment (2×200 mg) has proven very effective. Alternative antibiotics include josamycin and ciprofloxacin. Whenever fever, head and/or muscle pain occur combined with typical skin involvement, particularly an exanthem or an eschar, tick-bite fever should be taken into consideration as a differential diagnosis when travelers have returned from a region where rickettsiae are known to be transferred by tick-bites. In returning travelers from defined areas of the American continent, Rocky Mountain spotted fever should be considered because of its complicated course with a mortality rate up to 5%. That is why in all cases, immediate antibiotic therapy should be initiated. Only then a quick defervescence can be accomplished after a one-day antibiotics therapy.

Is SAPHO syndrome a target for antibiotic therapy?

The etiology of the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome remains unclear. Infectious factors are proposed to be relevant in the etiopathogenesis of the disease. To our knowledge, this is the first reported case of a proposed relationship between Staphylococcus aureus cultured from plantar pustule and SAPHO syndrome, which was successfully treated with co-trimoxazole (CTM) (sulfamethoxazole/trimetoprim). CTM might be the drug of choice for therapy for SAPHO syndrome because of combined antibiotic and immunomodulatory properties. Hypersensitivity testing of the medication in vitro was performed to identify, in the preclinical stage, the hypersensitivity reaction to CTM, which may have been severe.

Therapy for Acute Otitis Media-Reply

I believe that amoxicillin continues to be the drug of choice for therapy for acute otitis media. Ceftriaxone may be an alternative for selected patients. The following points are important in response to Dr Semones' comments: Ceftriaxone is not currently approved by the Food and Drug Administration for treatment of acute otitis media. If and when it is approved, its use should be considered for specific clinical circumstances, such as acute otitis media in a young infant who may also have bacteremia. Selective use of oral antibiotics for all indications should be fostered. We are unaware of any data that indicate that a single dose of ceftriaxone is more likely to foster development of resistant pathogens than a 10-day course of an oral antibiotic approved for therapy for acute otitis media.

Loperamid, an efficacious drug against fish-pathogenic acanthocephalans

A total of 20 drugs were tested for their efficacy in the treatment of infections involving the two major acanthocephalans infesting rainbow trout in European trout farms. In in vitro experiments, the antidiarrhoeic loperamid and the well-known anthelminthic drug niclosamide showed the best efficacy. Worms treated with loperamid contracted the posterior end of their body, in which severe necrosis of the tegument caused the death of the worms. In in vivo experiments, loperamid was the most efficacious drug: 50 mg/kg given to rainbow trout on 3 consecutive days led to a complete cure. According to preliminary tolerance tests in water baths, the toxicity of this drug is low as compared with that of niclosamide, which is very toxic. Thus, loperamid can be recommended as the drug of choice for therapy of acanthocephalan infections in fish.

Management for Interstitial Lung Disease: State of the Art

A survey of 109 pulmonary physicians representing both private practice and academic medicine was conducted to learn their practice of management and treatment of interstitial lung disease. Of the 109, 25 (23 percent) responded. Twenty-two of 23 routinely obtain tissue diagnosis. The routine method was transbronchial biopsy by 15 physicians vs open lung biopsy by seven. Few (n = 5) use BAL cell analysis. The majority of clinicians used two to four criteria to initiate therapy. Physiology laboratory data were the predominant criteria used by the majority of physicians and also were most commonly used to monitor a patient's course over time. Prednisone was the drug of choice for therapy. Immunosuppressive therapy was not used until failure of steroid therapy was observed. There was little consistency in the diagnostic procedures applied, criteria for the decision to treat, the drugs used to treat, or methods for monitoring.

Infectious syphilis mimicking neoplastic disease

Five patients who were initially evaluated for malignant neoplasm actually had infectious syphilis (one primary, two secondaries, two secondaries with persistence of primary). Two patients were considered for radical surgery and one for extensive radiation and/or chemotherapy. In four patients an elevated routine admission VDRL was the first indication of the correct diagnosis. Dark-field examination is the most important laboratory test in the diagnosis of primary syphilis; VDRL and FTA-ABS are most important in confirming secondary syphilis. Penicillin remains the drug of choice for therapy. At a time when the incidence of sexually transmitted diseases is increasing, it is extremely important to develop adequate educational programs for medical students and physicians. (<i>Arch Intern Med</i>137:156-160, 1977)

Infectious Syphilis Mimicking Neoplastic Disease

Five patients who were initially evaluated for malignant neoplasm actually had infectious syphillis (one primary, two secondaries, two secondaries with persistence of primary). Two patients were considered for radical surgery and one for extensive radiation and/or chemotherapy. In four patients an elevated routine admission VDRL was the first indication of the correct diagnosis. Dark-field examination is the most important laboratory test in the diagnosis of primary syphillis; VDRL and FTA-ABS are most important in confirming secondary syphillis. Penicillin remains the drug of choice for therapy. At a time when the incidence of sexually transmitted diseases is increasing, it is extremely important to develop adequate educational programs for medical students and physicians.

PREVENTION AND TREATMENT OF PNEUMOCYSTIS CARINII PNEUMONITIS (PCP)

In the immunosuppressed host the mortality rate for PCP is approximately 100% if untreated. Pentamidine isethionate is presently considered the drug of choice for therapy but has several disadvantages. The cortisone-treated rat provides an excellent model for the study of PCP. Three drugs, not previously investigated for effectiveness against P. carinii but with possible antiprotozoan activity, were studied. Sprague-Dawley rats were randomly assigned to 11 groups with 15 rats per group. Drugs were administered prophylactically at the initiation of immunosuppression with cortisone acetate. To evaluate therapeutic efficacy, drugs were administered after the first animal in each group had died with PCP. Lung sections taken after spontaneous death or sacrifice were examined histologically with the methenamine silver nitrate impregnation method. Whereas, all of the 15 untreated rats died with PCP, none of the 15 given trimethoprim-sulfamethoxazole (TS) prophylactically acquired the infection. After PCP was established, 9 of 14 rats recovered after treatment with TS compared to only 2 of 14 treated with pentamidine. Rifampin and clindamycin, separately, or in combination with pentamidine, were ineffective in the prevention and treatment of PCP. Since the animal studies clearly demonstrated that TS was effective in the prevention and treatment of PCP, we have treated to date 1 child with PCP and acute leukemia. Prompt and uncomplicated recovery followed the administration of TS orally.