Nocardia farcinica pericarditis after kidney transplantation despite prophylaxis

Abstract: A deceased-donor kidney transplant recipient developed purulent pericarditis caused by Nocardia despite trimethoprim–sulfamethoxazole (TMP–SMX) prophylaxis for Pneumocystis jirovecii . She was treated empirically with ceftriaxone and amikacin and subsequently underwent sternotomy with drainage of an intrapericardial abscess. Culture and susceptibility data demonstrated Nocardia farcinica , which was susceptible to SMX and amikacin, although resistant to ceftriaxone. Nocardia asteroides , the more common human pathogen, is generally susceptible to third-generation cephalosporins and TMP–SMX. N. farcinica is rare in the United States, more virulent and resistant than N. asteroides , and is more likely to cause disseminated disease. Successful therapy of disseminated Nocardia infections is dependent upon choice of appropriate empiric antibiotics in addition to surgical drainage of purulent fluid collections. TMP–SMX prophylaxis may not be sufficient to prevent infections due to Nocardia species in all immunosuppressed transplant recipients. Here, a rare complication of this unusual pathogen is discussed.     

Treatment of disseminated Mycobacterium avium complex infection in AIDS with amikacin, ethambutol, rifampin, and ciprofloxacin. California Collaborative Treatment Group

OBJECTIVE: To determine the efficacy of combination drug therapy for disseminated Mycobacterium avium complex infection in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Prospective, nonrandomized, before-after comparison. SETTING: Outpatient clinics at three university medical centers. PATIENTS: Seventeen patients with at least two consecutive blood cultures positive for M. avium complex who had not been previously treated with antituberculous medications. Fifteen of the seventeen patients completed at least 4 weeks of treatment. INTERVENTION: Patients received daily intravenous amikacin (7.5 mg/kg body weight) for the first 4 weeks plus the following oral medications for at least 12 weeks: ciprofloxacin, 750 mg twice daily; ethambutol, 1000 mg daily; and rifampin, 600 mg daily. MEASUREMENTS AND MAIN RESULTS: The baseline geometric mean colony count from blood cultures decreased from 537/mL to 14/mL (P less than 0.001) after 4 weeks of therapy. The microbiologic suppression was sustained while on treatment and was associated with a decrease in systemic symptoms related to M. avium complex infection. Premature withdrawal from treatment (less than 12 weeks) occurred in 7 of 17 patients. The commonest reasons for early withdrawal were gastrointestinal intolerance and hepatic toxicity. CONCLUSIONS: Mycobacterial load and systemic symptoms in patients with AIDS and disseminated M. avium complex infection can be effectively reduced by a regimen containing amikacin, ethambutol, rifampin, and ciprofloxacin.     

Failure of ceftriaxone in the treatment of acute brucellosis.

In an open, multicenter study conducted in Israel in 1989, 18 patients with acute brucellosis were randomized to receive either less than or equal to 2 g of intramuscularly administered ceftriaxone daily for at least 2 weeks or doxycycline for 4 weeks plus streptomycin for 2 weeks. All 10 patients treated with the combination of doxycycline plus streptomycin responded promptly, and their infections did not relapse during 6 months of follow-up. Of eight patients treated with ceftriaxone, six did not respond initially; when ceftriaxone was replaced by the combination of doxycycline and streptomycin, patients responded immediately. No relapses of infection were observed in these patients during follow-up. One patient who received ceftriaxone responded and remained well at the end of 6 months of follow-up, and one patient who initially responded to therapy with this drug experienced relapse of infection within 3 weeks but recovered when the doxycycline/streptomycin regimen was initiated. We conclude that despite encouraging data from in vitro studies and promising clinical studies, 2 g of ceftriaxone administered im daily should not be considered appropriate therapy for brucellosis.     

Efficacy of ofloxacin in treating typhoid fever

We studied 75 patients (36 males and 39 females), suffering from typhoid fever. 64 patients were treated with ofloxacin and 11 with amikacin, dosage regimens of the two drugs were 300 mg and 300-400 mg twice daily. Clinical effective rate was 100% with ofloxacin and 36.4% with amikacin. A total of 72 strains of salmonella typhi was isolated from all the patients of both groups. Bacteriological elimination rate was 100% with ofloxacin after treatment. Sensitive rates for S. Typhi isolated was 100% with ofloxacin, norfloxacin and ceftriaxone, 98.6% with amikacin and 20-21.4% with chloramphenicol, ampicillin and sulfamethoxazole Co. There were fewer adverse reactions and better acceptance, one had skin rash and one had gastrointestinal disturbance. In amikacin group, abnormality of urine routine and serum creatinine was observed. Ofloxacin was well absorbed orally. Its high bioavailability, satisfactory therapeutic efficacy excellent tolerability and convenience for use make it a very useful medication in the therapy of typhoid fever resulted from multiresistant strains.     

Treatment of nonpulmonary infections due to Mycobacterium fortuitum and Mycobacterium chelonei on the basis of in vitro susceptibilities

One hundred twenty-three patients with nonpulmonary infections due to Mycobacterium fortuitum or Mycobacterium chelonei were treated by wound debridement and with chemotherapy on the basis of in vitro susceptibilities of the organism. Of 76 patients with infections caused by M. fortuitum, 13 required no therapy or were adequately treated with surgery alone. Patients with active localized disease received single drug therapy (usually with a sulfonamide) for a mean period of 10.6 weeks for cellulitis and seven months for osteomyelitis. Patients with extensive disease received amikacin or amikacin plus cefoxitin (mean, four weeks) followed by a sulfonamide (mean, six months). The 47 patients with infections caused by M. chelonei received no therapy or were treated with surgery alone (6); with amikacin (10), erythromycin (6), doxycycline (3), or cefoxitin (1); or with amikacin plus cefoxitin followed by cefoxitin alone for a total of 10-12 weeks (20); or other multiple-drug regimens (1). Surgery was performed on 74 (60%) patients. Schlichter tests or serum drug levels were determined for 81 (66%) patients. Response to therapy was excellent; 68 (90%) infections with M. fortuitum and 34 (72%) with M. chelonei were successfully treated. Cultures became negative within six weeks of chemotherapy, except for sternal osteomyelitis, for which cultures were not negative until up to 14 weeks. Follow-up for a mean period of 12 months following therapy was possible in 80% of cases. Relapses were rare except in patients with disseminated disease, and drug resistance developed in only one patient. These studies demonstrate the value of routine susceptibility testing of these mycobacterial species and the benefit of chemotherapy on the basis of in vitro susceptibilities.     

Pulmonary nocardiosis re-visited: experience of 35 patients at diagnosis

Pulmonary infection by Nocardia is an uncommon opportunistic infection in humans. Thirty-five patients with pulmonary nocardiosis were identified in two tertiary referral hospitals. A retrospective review of the patient characteristics, clinical and laboratory features including antimicrobial susceptibility at diagnosis was carried out. Radiological features derived from chest radiographs and CT scans were also documented. In our population, the predominant risk factors were immuno-compromised state, corticosteroid therapy, and underlying pulmonary pathology. The presenting features were similar to those previously described but disseminated infection was not common. The radiological changes were diverse and non-specific. Nocardia asteroides was the commonest species. Most Nocardia isolates were susceptible to imipenem, ceftriaxone, amikacin, and cotrimoxazole. Co-existing microbial agents are common and reflect the underlying complex disorders.     

Disseminated Mycobacterium abscessus Infection Following Septic Arthritis: A Case Report and Review of the Literature

Mycobacterium abscessus is a rapidly growing mycobacterium found mainly in patients with respiratory or cutaneous infections, but it rarely causes disseminated infections. Little is known about the clinical characteristics, treatment, and prognosis of disseminated M abscessus infection.A 75-year-old Japanese woman who had been treated for 17 years with a corticosteroid for antisynthetase syndrome with antithreonyl-tRNA synthetase antibody developed swelling of her right elbow. X-ray of her right elbow joint showed osteolysis, and magnetic resonance imaging revealed fluid in her right elbow joint. M abscessus grew in joint fluid and blood cultures. She was diagnosed with a disseminated M abscessus infection following septic arthritis. Antimicrobial treatment by clarithromycin, amikacin, and imipenem/cilastatin combined with surgical debridement was administered. Although blood and joint fluid cultures became negative 1 week later, the patient died at 6 weeks from starting antimicrobial treatment.We reviewed 34 cases of disseminated M abscessus infections from the literature. Most of the patients had immunosuppressive backgrounds such as transplantation, use of immunosuppressive agents, hematological malignancy, and end stage renal disease. The duration from onset of symptoms to diagnosis was over 3 months in half of the cases. All fatal cases had positive blood cultures or use of immunosuppressive agents.Clinicians should bear in mind that mycobacterial infections including M abscessus are one of the differential diagnoses in patients with subacute arthritis and soft tissue infections.     

Ceftriaxone and amikacin as single daily dose in the empiric therapy for febrile episodes in neutropenic patients

One hundred thirty-three febrile episodes in 115 neutropenic patients with hematologic malignancies were empirically treated with ceftriaxone and amikacin in a single daily dose. An indwelling central venous catheter (CVC) was present in 44 cases. Septicemia was documented in 18 (41%) patients with CVC (13 gram-positive, 5 gram-negative and 1 fungus) and in 30 (34%) patients without CVC (19 gram-positive, 10 gram-negative and 2 fungi). Coagulase-negative staphylococcus was observed in 10 out of 19 blood isolates in the presence of a CVC and in 6 out of 31 blood isolates in patients without CVC. Empiric therapy was successful in 56.4% of cases. Improvement after the addition of vancomycin or teicoplanin was observed in 38.6% of cases with a CVC and in 13.5% of those without (p less than 0.02). Only two patients died from gram negative septicemia, and the substitution of ceftriaxone with another beta-lactam was necessary in only 6% of the cases. Empiric therapy with single daily-dose ceftriaxone and amikacin appears to be effective in febrile neutropenic patients; our data, however, show the high incidence of Staphylococcus epidermidis septicemia and the frequent need to add an anti-gram-positive drug in patients with an indwelling CVC.     

Ⅱ型糖尿病合并泌尿系感染尿细菌培养及药敏试验分析

目的探讨Ⅱ型糖尿病合并泌尿系感染尿细菌培养及药敏试验情况。方法对135例Ⅱ型糖尿病合并泌尿系感染患者的尿液进行分离培养及药敏试验。结果病人尿液革兰阴性杆菌阳性率为67．4％,革兰阳性球菌阳性率为25．2％。其中大肠埃希菌阳性率41．5％,酵母样真菌阳性率7．4％;革兰阴性杆菌对头孢曲松钠、丁胺卡那霉素和妥布霉素的敏感率分别为91．2％、85．7％和70．3％,革兰阳性球菌对万古霉素、头孢曲松钠和林可霉素的敏感率分别为79．4％、67．6％和55．9％。结论Ⅱ型糖尿病合并泌尿系感染尿细菌对部分抗生素耐药;临床上应合理使用抗生素。     

Diagnosis, clinical picture and treatment policy in acute progressive forms of pulmonary tuberculosis under present-day epidemiological conditions

Among 103 examinees, the most common clinical type was caseous pneumonia (45.6%), progressive fibrocavernous tuberculosis (20.4%), infiltrative caseous pneumonia (17.5%), disseminated tuberculosis (16.5%). Progression was characterized by cavern formation in 91.1% of patients, with large and giant caverns containing nonspecific microbes forming in 79.6%. All the patients were found to isolate bacteria and 93.5% showed their excess. Drug-resistant microbes were identified in 62.1% of patients; polydrug resistance was seen in 37.5%. Chemotherapy was performed at the first stage by using 5 drugs: isoniazid, rifampicin, pyrazinamide, ethambutol plus kanamycin or amikacin. A combination of reserve drugs, including prothionamide, ofloxacin (ciprofloxacin) amikacin, pyrazinamide, and ethambutol, was used in patients with polyresistance. Symptomatic and pathogenetic therapies should aim at correcting complications and concomitant abnormalities. Following 6 months, 80% of patients stopped isolating bacteria, the process became stable and they could be prepared for planned surgical treatment. In 20% of cases, the process was progressive and it required salvage operations.     

Gram-negative bacillary meningitis after cranial surgery or trauma in adults

In order to assess the clinical features, aetiology, treatment and outcome of post-neurosurgical and post-traumatic Gram-negative bacillary meningitis (GNBM) we performed a retrospective review of all adult patients admitted to the Department of Neurosurgery who had Gram-negative bacilli cultured from cerebrospinal fluid (CSF) following a neurosurgical procedure or traumatic head/spinal injury. During the 12 y of the review 33 patients had CSF isolates of Gram-negative bacilli that were thought to be significant. The median patient age was 47 y (range 22-77 y) and 21 (64%) were male. Klebsiella pneumoniae, Enterobacter cloacae and Escherichia coli were the most common isolates. Minimal inhibitory concentrations (MIC) measured for half the patients' isolates resulted in 5 regimen changes, including 2 patients with E. cloacae meningitis in whom cephalosporin susceptibility decreased during cephalosporin treatment. Our recommended initial treatment was intravenous ceftriaxone and amikacin, subsequently tailored by susceptibility results; approximately half the patients remained on the antibiotics they started and half were changed to an alternate regimen, most often a carbapenem. Five patients (15%) died, 1 dying after cure of his GNBM. There were no failures in those who received more than 12 d of appropriate treatment: treatment for at least 14 d after the last positive CSF culture guaranteed cure. Initial ceftriaxone and amikacin subsequently changing to susceptibility driven alternatives, often a carbapenem, resulted in cure of 85% of our patients with GNBM.     

Disseminated disease due to Mycobacterium chelonei treated with amikacin and cefoxitin. Absence of killing with either agent and possible role of granulocytes in clinical response

Disseminated disease due to rapidly growing mycobacteria is manifested by positive blood cultures and multiple skin and subcutaneous abscesses. A patient had T-cell lymphoma and disseminated disease; he also had neutropenia intermittently. Single-agent therapy with amikacin sulfate or cefoxitin sodium was not adequate during periods of neutropenia, and combination therapy was necessary to control the infection. Clinical response correlated with detectable serum inhibitory levels of the antimicrobial agents. Surprisingly, the organism was not killed by either amikacin or cefoxitin, a finding that correlated with the absence of serum bactericidal levels. This case suggests that granulocytes may play a role in the host's response to this organism, and determination of serum inhibitory and possible bactericidal levels may be useful in monitoring therapy.     

Effects of preventive, early, and late antifungal chemotherapy with fluconazole in different granulocytopenic models of experimental disseminated candidiasis

To investigate the potential use of fluconazole for prevention and treatment of disseminated candidiasis in granulocytopenic patients, its in vivo antifungal activity was studied in three models of disseminated candidiasis in persistently granulocytopenic rabbits: acute, subacute, and chronic disseminated candidiasis. Fluconazole was compared with the combination of amphotericin B and flucytosine for preventive, early, and late treatment of disseminated candidiasis, depending on the model. Fluconazole was most effective when used for preventive or early treatment of acute and subacute disseminated candidiasis. When compared with the combination of amphotericin B plus flucytosine, fluconazole was similarly effective in early treatment of acute and subacute disseminated candidiasis. When treatment was delayed 6 days after established infection, fluconazole was less active in clearing tissues in comparison with its activity in preventive and early treatment. The combination of amphotericin B plus flucytosine, however, was significantly more active than fluconazole in treatment of chronic disseminated candidiasis in all tissues. In summary, fluconazole was most effective against disseminated candidiasis in persistently granulocytopenic rabbits when used for prevention or early treatment.     

Amikacin therapy for gram-negative septicemia

Amikacin was administered to 18 patients with gram-negative septicemia. Ten of the patients had blood culture isolates highly resistant to gentamicin; six of these patients had persistent bacteremia while receiving gentamicin alone or in combination with other agents. Fourteen of the 18 patients were cured with amikacin therapy and adjunctive measures. Nine of the 10 patients with gentamicin-resistant pathogens were cured. The occurrence of nephrotoxicity in four patients with elevated amikacin serum levels and serious underlying disease indicates the desirability of monitoring serum amikacin levels. Minor ototoxicity occurred in two patients and was associated with prolonged therapy and high serum amikacin levels. Amikacin is a highly effective agent for treating patients with gram-negative bacteremia; it is the agent of choice in the therapy of patients with suspected or documented gram-negative bacteremia caused by pathogens resistant to gentamicin and susceptible to amikacin.     

Trimethoprim/sulfamethoxazole-resistant Nocardia asteroides causing multiple hepatic abscesses. Successful treatment with ampicillin, amikacin, and limited computed tomography-guided needle aspiration

Hepatic abscesses are rarely encountered in disseminated Nocardia infections. Sulfonamides alone or trimethoprim/sulfamethoxazole is often efficacious in treating infections caused by Nocardia asteroides. In vitro resistance of N. asteroides to trimethoprim/sulfamethoxazole is occasionally present. The patient described in this report had disseminated nocardiosis initially manifesting as multiple subcapsular hepatic abscesses. In vitro susceptibility studies demonstrated resistance to trimethoprim/sulfamethoxazole. Subsequent treatment with ampicillin and amikacin in conjunction with computed tomography-guided needle aspiration of several of the hepatic abscesses, surgical drainage of a right pleural empyema, and eventual discontinuation of use of corticosteroids resulted in cure of the infection.     

Candida and Aspergillus infections in immunocompromised patients: an overview

Infection is a major cause of morbidity and mortality in granulocytopenic patients. With the increasing use of aggressive chemotherapy causing prolonged granulocytopenia in patients with cancer, the risk of disseminated fungal infection has increased. Although Candida and Aspergillus species are known to be the most common fungal pathogens responsible for disseminated infection, diagnosis of such infection may be difficult. The use of empiric amphotericin B for presumed disseminated candida infection may reduce morbidity caused by this fungal pathogen; moreover, amphotericin B remains the agent of choice for established candida infection, although fluconazole shows promise. The addition of flucytosine may enhance the efficacy of amphotericin B against Candida. Aspergillus infection is more difficult to treat. Early recognition of invasive aspergillosis and use of high-dose amphotericin B (1.0-1.5 mg/[kg.d]) alone or in combination with flucytosine may reduce associated mortality. More active, less toxic antifungal agents are needed to improve the efficacy of treatment and prophylaxis of disseminated fungal infection.     

Infections due to Nocardia transvalensis: clinical spectrum and antimicrobial therapy.

Nocardia transvalensis, a rare Nocardia species, has previously been recognized as a cause of actinomycotic mycetoma. In a retrospective review of N. transvalensis isolates referred to the Centers for Disease Control (Atlanta) during the period January 1981 through January 1990, we identified 15 patient isolates. Four N. transvalensis isolates originated from one Australian reference laboratory; one patient's isolate that was identified by the Australian laboratory but that was not received at the Centers for Disease Control was also included in our study. A review of the cases of these 16 patients found that N. transvalensis caused infection in 10 patients and colonization in two patients. Six (75%) of eight patients with primary pulmonary or disseminated N. transvalensis infections had an underlying immunologic disorder or were receiving immunosuppressive therapy; three patients with disseminated infection died. All nine infected patients for whom specific antimicrobial therapy was prescribed received trimethoprim-sulfamethoxazole. Results of in vitro antimicrobial susceptibility tests of 11 N. transvalensis isolates revealed increased antimicrobial resistance to amikacin and other drugs when compared with that of other Nocardia species. Severely immunocompromised patients are predisposed to N. transvalensis pneumonia or disseminated infection, and the lung may be the portal of entry.     

Sensitivity of 523 blood culture isolates to 33 antibiotics

523 blood culture isolates collected during 18 months (July 1980-December 1981) were analysed by the agar dilution method for sensitivity to 33 antibiotics. Breakpoints corresponding to the SIR system were used but for N-formimidoyl-thienamycin (N-f-thienamycin), azthreonam and fosfomycin serial dilutions were made. Aminoglycosides (netilmicin, gentamicin, amikacin and tobramycin) inhibited from 90 to 86% of the strains. This was comparable to the percentage inhibited by some cephalosporins (cefotaxime, cefoperazone, ceftazidime, ceftriaxone, cefuroxime, cephamandole and moxalactam) ranging from 95 to 89%. A very high number of strains (99%) were inhibited by N-f-thienamycin. By combination of certain antibiotics more than 99% of the strains could be inhibited.     

Ceftriaxone therapy of chronic inflammatory arthritis. A double-blind placebo controlled trial

To determine whether chronic inflammatory arthritis may respond to antibiotic therapy (implying a bacterial origin), we conducted a placebo-controlled, double-blind study. Sixty patients with inflammatory arthritis and antibody titers to Borrelia burgdorferi 1:64 or more were randomized to receive placebo (n = 20) or 2 g/d of ceftriaxone intravenously (n = 40) for 2 weeks. Two of 20 placebo- and 19 of 40 antibiotic-treated patients improved. At 1 month, the placebo-treated patients could elect to receive ceftriaxone. Altogether, 58 patients were treated with ceftriaxone and followed up for 13 to 24 months. Improvement was noted in 27 of the 58 antibiotic-treated patients. Patients with a wide diversity of inflammatory arthritis were studied. Response to ceftriaxone was seen in all groups, including 5 of 12 with rheumatoid arthritis, 5 of 8 with psoriatic arthritis, 3 of 5 with vasculitis, and 14 of 33 with less well-differentiated chronic inflammatory arthritis. In 16 of the 27 who responded to the antibiotic, the arthritis worsened 6 to 18 months after the initial response to ceftriaxone. Previous improvement of arthritis after oral antibiotic was a better predictor of response to ceftriaxone than either duration of disease or Lyme antibody titer. Side effects to ceftriaxone were frequent and included diarrhea (29/60) and acute allergic reactions (9/58). We conclude that some patients may have an occult bacterial infection underlying their chronic inflammatory arthritis, and may respond to antibiotic therapy. The response to ceftriaxone in patients with even weakly reactive Lyme titers encourages further prospective placebo-controlled studies of antibiotics in various subsets of chronic arthritis.     

Piperacillin–Tazobactum Plus Amikacin Versus Ceftazidime Plus Amikacin as Empirical Therapy for Fever in Neutropenic Patients with Hematological Malignancies

Infections are one of the main cause of death in cancer patients particularly when granulocytopenia is present. A number of drugs have been used for the treatment of neutropenic patients with fever. Most published literature has shown piperacillin–tazobactum in combination with amikacin to be significantly more effective than ceftazidime plus amikacin in empirical treatment of febrile episodes in patients with neutropenia. In view of the reported literature we have tried this combination in our febrile neutropenic patients with haematological malignancies at PGIMS Rohtak. It was an open randomized trial. Patients were divided into two groups of 20 each. In the first group (group A) piperacillin–tazobactum (4 + 0.5 g 6 hourly) with single daily dose of amikacin 20 mg/kg was given. In the second group (group B) ceftazidime 40 mg/kg every 8 hourly with single daily dose of amikacin 20 mg/kg was given. The most common site of infection was blood followed by urinary tract, respiratory tract and oral cavity. 13 (65%) patients in group A and 12 (60%) patient in group B showed clinical success. In our study however in our patients a better response was seen in patients with piperacillin–tazobactum + amikacin (65% vs. 60%). So it is recommended that piperacillin–tazobactum + amikacin should be given in febrile neutropenic patients with haematological malignancies.