amphotericin-b and Pneumonia--Bacterial

Pneumonia complicates the course of 50% of patients on mechanical ventilation, requiring three or more days of mechanical ventilation and potentially increasing the relative risk of mortality by 20-40%. The predominant potentially pathogenic micro-organisms are Streptococcus pneumoniae, Staphylococcus aureus (sensitive to methicillin in the previously healthy host), Pseudomonas aeruginosa (aerobic gram-negative bacilli), and methicillin-resistant Staphylococcus aureus in the host with underlying disease. Approximately 85% of pneumonias are endogenous, caused by bacteria present in the patient's oropharyngeal flora. Bacteria present on admission cause primary endogenous pneumonia (55%), whereas bacteria acquired in the unit lead to supercarriage or secondary carriage and subsequently secondary endogenous pneumonia (30%). The remaining 15% are exogenous, ie the bacteria causing pneumonia are not carried by the patient. The diagnosis is usually based on clinical, radiological, and microbiological criteria, using the non-invasive method of tracheal aspirate, which yields >/=10(5) micro-organisms. Seven randomized trials have evaluated three non-antibiotic prophylactic maneuvers: hygiene (1 trial), subglottic drainage (4 trials), and semirecumbent position (2 trials). The impact on pneumonia was mixed, whereas mortality was unchanged. Selective digestive decontamination, using parenteral and enteral antimicrobials to control the three types of pneumonia, has been evaluated in 54 trials and showed an absolute mortality reduction of 8%. The therapy of pneumonia relies on six basic principles: (a) surveillance and diagnostic cultures to identify micro-organisms; (b) immediate and adequate antibiotic treatment to sterilize the lower airways, (c) the source of potential pathogens requires elimination for recovery of the original infection and prevention of relapses and/or superinfections; (d) aerosolized antimicrobials; (e) removal or replacement of the endotracheal tube; and (f) surveillance samples are indispensable to monitor efficacy of treatment. The aim of our review was to evaluate up to date facts regarding control of bacterial pneumonias during mechanical ventilation in intensive care unit settings.

Topics: Amphotericin B; Anti-Bacterial Agents; Cefotaxime; Chemoprevention; Cross Infection; Equipment Contamination; Humans; Hygiene; Intensive Care Units; Length of Stay; Pneumonia, Bacterial; Polymyxin B; Respiration, Artificial; Tobramycin

The antimicrobial management of patients in the critical care unit is complex. Not only must the clinician be familiar with a number of clinical, microbiological, pharmacological, and epidemiological observations but also fundamental pharmacodynamic concepts. It is an understanding of these concepts that forms the basis for the design of dosing strategies that maximize clinical efficacy and minimize toxicity. Antimicrobial selection is further complicated by the plethora of new antimicrobial agents available with varying clinical utility. Nowhere is this more evident than in the quinolone class of antibiotics. To aid the clinician in differentiating between quinolones it now seems reasonable to create a classification system akin to the generation grouping applied to the cephalosporins. Our classification is based upon the pharmacodynamic principles discussed within this article.

Topics: Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Community-Acquired Infections; Cross Infection; Fluoroquinolones; Humans; Intensive Care Units; Mycoses; Pneumonia, Bacterial; Skin Diseases, Bacterial; Soft Tissue Infections; United States; Urinary Tract Infections

The combination of liposomes and aerosols has been utilized to directly target the lungs with chemotherapeutic agents that might not have been used because of low solubility or toxicity. There are a variety of antibacterials, antifungals, and antivirals that have good in vitro activity, but are not effective because of their systemic toxicity and/or poor penetration into the lungs. Incorporation of many lipophilic drugs into liposomes decreases their toxicity without affecting effectiveness, thus increasing the therapeutic index. We have focused on aerosol delivery of amphotericin B (ampB) for the treatment of pulmonary and systemic fungal diseases. We have tested a variety of ampB-lipid formulations for the optimal treatment regimen for Cryptococcus and Candida infections in mouse models. The AeroTech II nebulizer (MMADs of 1.8-2.2 microns) produced aerosols with the highest concentrations in the breathable range. Pharmacokinetic studies revealed that pulmonary drug was present for hours to weeks. AmBisome retained its anticryptococcal activity even when animals were challenged 14 days after aerosol treatment. Aerosols may also be effective in systemic diseases. In our Candida-mouse model, systemic candidiasis and mortality were reduced by aerosolized ampB-liposome treatment. The ability to utilize lipophilic drugs, to deliver high concentrations of drug directly to the site of infection, and to reduce toxicity makes aerosol liposomes an attractive, alternative route of administration.

Topics: Aerosols; Amphotericin B; Animals; Anti-Infective Agents; Antifungal Agents; Humans; Liposomes; Lung Diseases, Fungal; Mice; Pneumonia, Bacterial; Pneumonia, Viral

We analyzed the 67 of 278 patients with newly-diagnosed AML or 'high-risk' MDS, treated in 1994 and 1995, who developed pneumonia during course 1 of their induction therapy. Pneumonia responded to treatment in 66%, but outcome depended on when pneumonia was diagnosed. Patients with pneumonia diagnosed during week 1 or 2 (group 2 patients) had the lowest response rate (43%). Patients who developed pneumonia in the 3rd week after treatment initiation had the best outcome with all 16 patients recovering. Patients presenting with pneumonia had an intermediate response rate (75%). The different patient groups were comparable with regard to age, underlying disease, prophylactic therapy, and G-CSF application. Although a lower CR rate was not entirely responsible for the lower response rate in group 2, failure to achieve CR predicted unsuccessful treatment of pneumonia in all groups. Fungal pathogens appeared more common in group 2 patients. However, in these patients, administration of amphotericin B was associated with a significantly higher failure rate (15/21 failures vs 2/9 who received no amphotericin B). We conclude that patients who develop pneumonia during week 1 or 2 are a high-risk group, and that use of amphotericin B indicates a particularly poor prognosis, although we present data suggesting that earlier use of amphotericin might be beneficial. Furthermore, since achievement of CR was an important prognostic factor in all groups, WBC transfusions particularly from donors given G-CSF should be considered as a therapeutic option. Finally, since time to failure of induction therapy and time to CR were similar in high-risk patients, new chemotherapy regimens could potentially improve both the CR rate and the outcome of pneumonia.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Humans; Leukemia, Myeloid; Middle Aged; Myelodysplastic Syndromes; Pneumonia, Bacterial; Remission Induction; Risk Factors

Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Aortic Aneurysm, Abdominal; Aortitis; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Clostridium Infections; Coccidioidomycosis; Device Removal; Enterobacter cloacae; Enterobacteriaceae Infections; Fluconazole; Humans; Magnetic Resonance Angiography; Male; Pneumonia, Bacterial; Postoperative Complications; Prosthesis-Related Infections

We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17-27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Ampicillin; Anti-Infective Agents; Bacterial Infections; Ceftriaxone; Child; Cohort Studies; Cryptococcosis; Emergencies; Female; Gentamicins; Histoplasmosis; Humans; Infections; Macrolides; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Respiratory Distress Syndrome; Shock, Septic; Tanzania; Tetracycline; Young Adult

Immunosuppressive agents increase the vulnerability of solid organ transplant patients to opportunistic infections. An atypical clinical presentation of a bacterial and fungal co-infection makes diagnosis and treatment even more challenging in this population. A 54-year-old hypertensive woman underwent a cadaveric kidney transplant after years on hemodialysis. Her treatment included mycophenolate, tacrolimus, and prednisone. By post-transplant week 8, she had pneumonia followed by progressive visual changes and seizures. Diagnostic work-up, consisting of magnetic resonance imaging of the brain and chest x-ray, showed several cerebral ring-enhancing lesions, and a pulmonary cavitary lesion. Disseminated nocardiosis was suspected and therapy was started. Skin biopsy was taken from a nodular lesion and culture confirmed Nocardia species infection. During hospitalization, neurological deficit persisted with worsening of brain lesions. She underwent excision of a brain abscess and the final pathologic report showed mucormycosis, revealing the patient's co-infection by 2 different pathogens. After therapy with liposomal amphotericin B and posaconazole, she has remained stable for more than 1 year. Disseminated nocardiosis masked and delayed the diagnosis and treatment of a more aggressive and worrisome organism. Mucormycosis, as a non-fatal isolated brain abscess without rhinal involvement, is an atypical presentation, and only a few cases have been reported.

Topics: Amphotericin B; Antifungal Agents; Brain Abscess; Coinfection; Female; Humans; Kidney Transplantation; Middle Aged; Nocardia; Nocardia Infections; Opportunistic Infections; Pneumonia, Bacterial; Radiography; Triazoles; Zygomycosis

A 46-year-old previously healthy woman was diagnosed with acute lymphoblastic leukaemia. The induction phase was complicated by alpha-haemolytic streptococcal bacteremia which responded to antibacterial therapy. Subsequently, the patient developed pneumonie due to Chlamydiapneumoniae which responded to macrolides. Following this infection the patient developed recurrent fever and new pulmonary infiltrates were noted. Bronchoscopy was performed and treatment was administered with liposomal amphotericin B (L-AmB, AmBisome) for two days, but was complicated by acute renal failure. Aspergillus fumigatus was cultured from bronchoalveolar lavage fluid [corrected] L-AmB was discontinued and voriconazole and caspofungin were administered. Despite aggressive antifungal therapy the patient developed progressive invasive infection, with central nervous system involvement as well as lesions appearing in the kidneys and liver. The patient died one week following the diagnosis of aspergillosis.

Topics: Acute Kidney Injury; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bacteremia; Caspofungin; Chlamydophila Infections; Chlamydophila pneumoniae; Doxorubicin; Drug Resistance, Multiple, Fungal; Drug Therapy, Combination; Echinocandins; Fatal Outcome; Female; Humans; Immunocompromised Host; Lipopeptides; Liposomes; Lung Diseases, Fungal; Medical Futility; Methotrexate; Middle Aged; Neuroaspergillosis; Peptides, Cyclic; Pneumonia, Bacterial; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Pyrimidines; Streptococcal Infections; Triazoles; Vincristine; Voriconazole

Corynebacterium striatum is a rare, but likely underreported, cause of serious infections in immunocompromised hosts and generally is susceptible to multiple classes of antimicrobial agents. Here we report the first case of C. striatum infection in a solid organ transplant recipient. Three years after heart transplantation, a 58-year-old man developed bilateral pneumonia and pulmonary embolism. He did not improve with levofloxacin, piperacillin/tazobactam, and heparin treatment. A homogeneous population of abundant gram-positive rods was repeatedly demonstrated in sputum and bronchoalveolar lavage fluid, and C. striatum was grown in pure culture. The isolate was unusual for its multidrug-resistant (MDR) antimicrobial susceptibility pattern. The pneumonia resolved with 4 weeks of vancomycin therapy, in combination with rifampin given only during the first 2 weeks of treatment. The isolation of coryneforms ("diphtheroids") is often attributed to contamination. Their abundant presence on direct examination of specimens and/or their growth in pure culture suggest a pathogenic role, however, and indicate the need for accurate microbiological identification, particularly in immunocompromised hosts who have been hospitalized and previously treated with antibiotics. Combination therapy that includes vancomycin may be the most prudent treatment for MDR C. striatum infections.

Topics: Amphotericin B; Ciprofloxacin; Corynebacterium; Corynebacterium Infections; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Heart; Heart Transplantation; Humans; Male; Pneumonia, Bacterial; Radiography

Systemic mycosis is among the most feared opportunistic infections in the immunocompromised host. Difficulty and delay in diagnosis and treatment often result in poor outcomes. In this communication a metastatically spreading form of subcutaneous aspergillosis developed in a patient with a history of allogeneic stem cell transplantation for relapsed Hodgkin's lymphoma. Strikingly, necrotizing cutaneous papules or ulcerating lesions were absent. Diagnosis was accomplished after excision of a clinically non-suggestive subcutaneous nodule. Despite prompt initiation of antimycotic therapy the outcome was fatal; dosage of conventional and liposomal amphotericin B was limited due to treatment-related toxicities. This case report describes a novel form of aspergillosis and underlines the need for an aggressive diagnostic approach in severely immunocompromised patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bleomycin; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dacarbazine; Deoxycytidine; Dexamethasone; Doxorubicin; Etoposide; Fatal Outcome; Gemcitabine; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Immunocompromised Host; Klebsiella Infections; Klebsiella pneumoniae; Lung Diseases, Fungal; Male; Melphalan; Neoplasm Recurrence, Local; Opportunistic Infections; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Prednisone; Procarbazine; Salvage Therapy; Skin; Transplantation, Homologous; Vinblastine; Vincristine

We report on a 32-year old HIV-infected male patient who was admitted to the hospital in a comatose state. A cryptococcus neoformans septicemia with meningoencephalitis was diagnosed. Intravenous treatment with amphotericin B was initiated and replaced three weeks later by fluconazole per os. With this therapy the patient recovered quite well. However, following two grand mal epileptic seizures he suddenly fell into a deep coma 22 days after admission to the hospital. The cause of the encephalopathy remained unclear, and the patient died 2 days later. Autopsy revealed a severe meningoencephalitis and a pneumonia due to cryptococcus neoformans. Departing from this case we discuss diagnosis, clinical presentation and treatment of cryptococcus meningoencephalitis.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Cryptococcus neoformans; Epilepsy, Tonic-Clonic; Fatal Outcome; Fluconazole; HIV Infections; Humans; Injections, Intravenous; Male; Meningoencephalitis; Pneumonia, Bacterial; Sepsis

Invasive fungal infections occur frequently in neutropenic patients although only in recent years has the role of emerging fungi been clearly established. We describe two cases of fungemia caused by Trichosporon beigelii and Rhodotorula glutinis respectively in two neutropenic patients with hematological malignancies who were treated with amphotericin B. The first patient, with refractory multiple myeloma, died following massive pneumonia despite therapy with amphotericin B and granulocyte-colony stimulating factor (G-CSF); the second patient, with relapsed acute lymphatic leukemia and persistent fever without any other clinical evidence, finally recovered. Amphotericin B continues to be considered the "gold standard" in the treatment of invasive mycoses although other approaches need to be tested for refractory infections.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Female; Fungemia; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged; Multiple Myeloma; Neoplasm Recurrence, Local; Neutropenia; Pneumonia, Bacterial; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pseudomonas Infections; Rhodotorula; Treatment Outcome; Trichosporon

The study included 6 children (aged 4-14 years) receiving a conditioning regimen for bone marrow transplantation (BMT) and 14 children (aged 2 14 years) with bone marrow transplants (13 allogeneic, 1 autologous). The children underwent flexible fibre-optic bronchoscopy (FFB) with bronchoalveolar lavage during 6 and 17 episodes of pneumonia, respectively. The aim was to compare the results of the two groups with respect to bronchoscopy findings, pneumonia-causing agents and outcome. During the conditioning regimen, the aetiological agents were recovered by bronchoscopy in 1/6 (17%) episodes and revealed by autopsy in another episode. In three episodes where the aetiology was uncertain, bacterial pneumonia was suspected in two, and Candida pneumonia in one. In episodes after transplantation the aetiological agents were recovered from bronchoscopy material in 14/17 (82%) patients. Autopsy confirmed the premortal diagnosis in the four children who died. In three episodes, bacterial pneumonia was clinically suspected. Based on clinical manifestations, FFB and autopsy findings, bacterial and fungal pneumonia were the most common diagnoses both during conditioning and after BMT. Fungal pneumonia was the most common cause of death in both groups.

Topics: Adolescent; Amphotericin B; Antibodies, Monoclonal; Antifungal Agents; Aspergillus fumigatus; Bone Marrow Transplantation; Bronchoalveolar Lavage; Bronchoscopy; Candida albicans; Child; Child, Preschool; Ciprofloxacin; Cytomegalovirus; Female; Humans; Lung; Male; Pneumonia, Bacterial

A 35-year-old woman was admitted to our hospital because of a fever and a productive cough. She had undergone renal transplantation and had taken immunosuppressive drugs, a steroid, inhaled amphotericin-B, and pentamidine. She was treated with ganciclovir, because infection with cytomegalovirus was suspected but her symptoms did not resolve. A chest X-ray film and a computed tomogram showed an infiltrative shadow in the right lower lung field. Specimens obtained by transbronchial lung biopsy showed lipid-laden macrophages and oil droplets in alveolar spaces. Organisms of the genus nocardia were isolated from bronchial lavage fluid. The final diagnosis was lipoid pneumonia combined with pulmonary nocardiosis. After treatment with Imipenem.cilastatin sodiom, Exacin and Sulfamethoxazole.trimethoprim, her symptoms and the infiltrative shadows on the chest X-ray film resolved. We believe that this patient had an exogenous lipoid pneumonia caused by inhalation of deoxycholic acid in amphotericin-B solubilized liquid, in addition to pulmonary nocardiosis.

Topics: Administration, Inhalation; Adult; Amphotericin B; Antifungal Agents; Female; Humans; Kidney Transplantation; Nocardia Infections; Pneumonia, Bacterial; Pneumonia, Lipid