Direct response question. This is a patient undergoing chemotherapy with respiratory symptoms and the "halo sign" on X-ray, very suggestive of invasive pulmonary aspergillosis. Treatment is with voriconazole. Aspergillus is resistant to fluconazole, so it would not be a valid option.

A patient undergoing chemotherapy for leukemia is admitted for pneumonia for which treatment with cefepime has been prescribed. A chest X-ray/CT scan shows an infiltrate with halo sign and crescentic meniscus. The lesion is peripheral and a transthoracic puncture is indicated for sampling. Pending definitive histologic and microbiologic results, what antimicrobial would you add to the treatment?

[Pulmonary infection in neutropenia].

MEDICAL HISTORY AND CLINICAL COURSE: A 42-year-old patient with hairy cell leukemia had been treated for 3 years by a hematologist in private practice. Initially the patient received 1 course of cladribine upon which the disease went into complete remission. 6 weeks ago a relapse was diagnosed and combination therapy with cladibrin and rituximab was initiated. Now the patient presented to the emergency room with shortness of breath and pain when breathing. In the chest x-ray, patchy infiltrates and pleural effusions were found on both sides. The subsequently performed computed tomography showed bilateral compactions with an Halo suspicious for fungal infiltrates. Upon admission to the hospital, an empirical antibiotic therapy with clarithromycin and piperacillin/tazobactam was initiated, which was later escalated to meropenem and linezolid. Additionally, an antifungal therapy with voriconazole was started and later switched to liposomal amphotericin B. At his admission, a positive aspergillus antigen could be detected in the microbiological laboratory. Under antimycotic treatment the aspergillus antigen was repeatedly negative. The patient presented with pronounced cytopenias and after a switch of therapy to vemurafenib and filgrastim, the hematopoiesis could only be stimulated insufficiently. The patient was transferred to the intensive care unit three days after admission with severe respiratory failure. He died on day 8 after admission. AUTOPSY AND DIAGNOSIS: Diagnosis was consistent with relapse of hairy cell leukemia with positive BRAF mutation and a bone marrow infiltration > 80 %. Autopsy revealed a significant hepato-splenomegaly, a lack of erythro-, granulo- and thrombopoiesis. Clots interspersed with fungal hyphae were found in both lungs and an infarction of the spleen with evidence of fungal hyphae was detected. The cultural findings post mortem on yeast or mold were negative. Patients with refractory hairy cell leukemia and prolonged neutropenia are at increased risk for systemic fungal infections. Therefore, prohylactic antimycotic therapy should be considered early in this group of patients. The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option. In the present case, the patient could unfortunately not be stabilized due to the septic complications.

Likelihood of inadequate treatment: a novel approach to evaluating drug-resistance patterns.

To provide a novel way to predict the likelihood that antibiotic therapy will result in prompt, adequate therapy on the basis of local microbiological data. Prospective study conducted at 3 medical intensive care units at the Viennese General Hospital, a tertiary care medical university teaching hospital in Vienna, Austria. One hundred one patients who received mechanical ventilation and who met the criteria for having ventilator-associated pneumonia. Fiberoptic bronchoscopic examination was performed, and bronchoalveolar samples were collected. Samples were analyzed immediately by a single technician. Minimum inhibitory concentrations were determined for imipenem, cephalosporins (cefepime and cefpirome), ciprofloxacin, and piperacillin-tazobactam, and drug resistance rates were calculated. These drug resistance rates were translated into the likelihood of inadequate therapy (LIT; the frequency of inadequately treated patients per antibiotic and drug-resistant strain), cumulative LIT (the cumulative frequency of inadequately treated patients), and syndrome-specific LIT. Among the 101 bronchoalveolar samples, culture yielded significant (at least 1 x 10(4) colony-forming units per mL) polymicrobial findings for 34 and significant monomicrobial findings for 31; 36 culture results were negative. Of the isolates from patients with ventilator-associated pneumonia who had monomicrobial culture findings, 33% were gram-positive bacteria and 20% were gram-negative bacteria. LIT suggested that 1 of 2 patients was treated inadequately for Pseudomonas aeruginosa infection. The LIT for patients with ventilator-associated pneumonia revealed that the rank order of antibiotics for appropriate therapy was (1) imipenem, (2) cephalosporins, (3) ciprofloxacin, and (4) piperacillin-tazobactam. These calculations were based solely on microbiological data. The novel ratio LIT may help clinicians use microbiological data on drug resistance to predict which antimicrobial agents will provide adequate therapy. In daily practice, this new approach may be helpful for choosing adequate antimicrobial therapy.

Hospital-acquired pneumonia

In 2005, the American Thoracic Society and Infectious Diseases Society of America have published guidelines suggesting antibiotics specifically for HCAP. The guidelines recommend combination therapy with an agent from each of the following groups to cover for both Pseudomonas aeruginosa and MRSA. This is based on studies using sputum samples and intensive care patients, in whom these bacteria were commonly found. cefepime, ceftazidime, imipenem, meropenem or piperacillin–tazobactam; plus ciprofloxacin, levofloxacin, amikacin, gentamicin, or tobramycin; plus linezolid or vancomycin In one observational study, empirical antibiotic treatment that was not according to international treatment guidelines was an independent predictor of worse outcome among HCAP patients.

Successful voriconazole treatment of invasive pulmonary aspergillosis in a patient with acute biphenotypic leukemia.

A 23-year old woman with acute biphenotypic leukemia (ABL) complained of chest pain with cough, high fever and hemoptysis during induction chemotherapy, although she had been treated with anti-biotics and micafungin. We made a clinical diagnosis of invasive pulmonary aspergillosis (IPA) based on a consolidation in the right upper lung field on a chest radiograph as well as a high level of serum beta-D-glucan (with no evidence of tuberculosis and candidiasis). We changed her treatment from micafungin to voriconazole. Later, we discovered an air-crescent sign by CT scan that supported the diagnosis of IPA. Following voriconazole treatment, clinical symptoms ceased and abnormal chest shadows improved gradually and concurrently with a recovery of neutrophils. IPA must be considered in immunocompromised patients with pulmonary infiltrates who do not respond to broad-spectrum antibiotics. Serological tests and CT findings can aid in early diagnosis of IPA, which, along with treatment for IPA, will improve clinical outcomes.

[A well-inked pneumonia… can you decrypt it?]

We report a case of pneumonia associated with necrotic mediastinal lymph nodes in an immunocompetent patient. The case report illustrates the difficulties in making a diagnosis in necrotic mediastinal lymph nodes and discusses strategies to optimize sampling. A 21-year-old immunocompetent woman was admitted to hospital with dyspnea and fever occurring ten days after delivery. Physical examination, biological results and chest X-ray led to the diagnosis of right upper lobe pneumonia. Treatment with three broad-spectrum antibiotics was ineffective. Thoracic CT-scan showed compressive mediastinal and hilar necrotic adenopathies and consolidation of the right upper lobe. Bronchoscopy with bronchoalveolar lavage and transbronchial needle aspiration was non-diagnostic. A second bronchoscopy with bronchoalveolar lavage and transbronchial needle aspiration performed in close collaboration with the mycology laboratory led to the diagnosis of cryptococcosis. Antifungal therapy with fluconazole resulted in a complete resolution of clinical and radiological signs. Although it is extremely rare, pulmonary cryptococcosis should be considered in immunocompetent patients presenting with necrotic pneumonia. Effectiveness of lymph node sampling can be improved by collaboration between clinicians and microbiologists.

Aspiration pneumonia

Treatment The main treatment of aspiration pneumonia revolves around the use of antibiotics to remove the bacteria causing the infection. Broad antibiotic coverage is required to account for the diverse types of bacteria possibly causing the infection. Currently recommended antibiotics include clindamycin, meropenem, ertapenem, ampicillin/sulbactam, and moxifloxacin. Treatment with piperacillin/tazobactam, cefepime, levofloxacin, imipenem, or meropenem is recommended in cases of potential antibiotic resistance. The typical duration of antibiotic therapy is about 5 to 7 days. If there is a large accumulation of fluid within the lungs, drainage of the fluid may also aid in the healing process.

Phialemonium curvatum

Other infections Phialemonium curvatum is known to cause vascular infection in patients undergoing hemodialysis. One of the sources of contamination was found to be contaminated water; other sources may have been renal grafts and bone marrow transplants. There was a report of P. curvatum affecting the lower spine and respiratory system and causing an abscess with purulent material in the middle. The course of treatment included antifungal medications, such amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and caspofungin, as well as removal of the cyst. References Fungi described in 1983 Sordariales

Febrile neutropenia

In 2010, updated guidelines were issued by the Infectious Diseases Society of America, recommending use of cefepime, carbapenems (meropenem and imipenem/cilastatin), or piperacillin/tazobactam for high-risk patients and amoxicillin-clavulanic acid and ciprofloxacin for low-risk patients. Patients who do not strictly fulfill the criteria of low-risk patients should be admitted to the hospital and treated as high-risk patients. Research to compare antibiotic treatments currently recommended in consensus guidelines identified 44 studies comparing different antibiotics. Significantly higher mortality was reported for cefepime compared to all other antibiotics combined. Piperacillin/tazobactam resulted in lower mortality than other antibiotics. Piperacillin/tazobactam might be the preferred antibiotic for the treatment of cancer patients with fever and neutropenia, while cefepime should not be used.

[A case of ventilator-associated pneumonia caused by Cupriavidus pauculus].

Cupriavidus pauculus (formerly CDC Group IVc-2) is a non-fermentative, motile, gram-negative bacillus, rarely associated with human infections. It has been isolated from water, water from ultrafiltration systems and bottled mineral water. To date, 19 cases of bacteremia, two cases of peritonitis and one case of tenosynovitis associated with C. pauculus have been reported in English literature. In this paper, we report the first case of C. pauculus ventilator-associated pneumonia (VAP) in Turkey. A 47 years-old female with breast cancer was performed total mastectomy six years ago and received six cures of chemotherapy after surgery. The patient was hospitalized in medical oncology clinic with complaints of weight loss, nausea and vomiting for one year. Since she had problems of consiousness, dysphagia and pitosis, lumbar puncture was performed to rule out central nervous system infection or metastasis. Cryptococcal meningitis was diagnosed upon the examination of Indian-ink stained smear of cerebrospinal fluid and amphotericin B was initiated. On the 11th day of her follow up, she developed respiratory distress and was transferred to pulmonary intensive care and underwent invasive mechanical ventilator (IMV) therapy. On the 4th day of IMV; a new infiltration was detected on the upper zone of chest X-ray in addition to fever (38.3 degrees C) and intense endotracheal secretion. Therefore, bronchoscopic examination was performed and bronchoalveolar lavage and bronchoscope aspiration materials were obtained and cultivated. Bacteria grown at blood agar and EMB agar after 48 hours of incubation were stained as gram-negative bacilli and identified as C. pauculus by VITEK 2 compact system (bioMérieux Inc, USA). The strain was susceptible to ceftazidime, ciprofloxacin, imipenem, trimethoprim-sulfamethoxazole, piperacilin/tazobactam and resistant to amikacin. The case was considered as C. pauculus VAP and imipenem (500 mg, 4 x 1) for 14 days was initiated. Clinical and microbiological resolution was achieved by imipenem therapy. In conclusion, rare pathogens like C. pauculus should be considered among the possible causative agents in infections that develop in immunocompromised host.

Piperacillin

Pneumonia The piperacillin-tazobactam (piptaz) antibiotic commonly used with an aminoglycoside retains similar levels of drug safety and efficacy as other antibiotic combinations such as ceftazidime with the aminoglycoside tobramycin in the treatment of patients with hospital acquired pneumonia. In a clinical comparison primarily targeting patients not initially placed in intensive care units, piperacillin-tazobactam was found to produce higher clinical and microbiological rates of success. By contrast, the drug efficacy of ceftazidime and piperacillin-tazobactam resulted in similar response rates (61.5% and 63.9 respectively) when tobramycin was added into both groups. Identical evaluations are shown when compared to the imipenem and tobramycin combination, where the administration of piperacillin-tazobactam on patients (especially those under mechanical ventilation) was only consisted of a slightly higher response rate.

Case report: Simultaneous occurrence of primary pulmonary lymphoma and opportunistic infections in a patient with chronic myeloid leukemia.

The occurrence of primary pulmonary lymphoma (PPL) as a secondary malignancy in patients diagnosed with chronic myeloid leukemia (CML) is extremely rare. As the clinical manifestations are atypical, most patients with PPL tend to be misdiagnosed with pneumonia. When the radiographic features of PPL and pulmonary infection overlap, clinicians can be confused about the diagnosis. Here, we report the first case of coexistence of PPL and opportunistic infections in a patient with CML in chronic phase (CML-CP). A 55-year-old woman presented with three weeks of hemorrhage of the oral mucosa at the Department of Hematology. After undergoing various examinations, she was diagnosed with CML-CP and was started on imatinib (400 mg/daily). Due to sudden respiratory distress, the patient was admitted to the respiratory intensive care unit 11 months later. Chest computed tomography (CT) revealed ground-glass opacities, patchy shadows, and multiple nodules in both lungs and enlarged mediastinal lymph nodes. The combination of biapenem and voriconazole antibiotic treatments was effective. The patient's respiratory distress was relieved, but there was intermittent coughing. In the following time, the patient developed a fever, and the imaging findings indicated progression of the disease in both lungs. Bronchoalveolar lavage (BAL) identified pathogens of multiple opportunistic infections. The coexistence of lymphomatoid granulomatosis (LYG) was not confirmed in this patient until a second CT-guided biopsy was performed. Ultimately, the patient underwent chemotherapy in time and is currently alive today. When the patient's recurrent respiratory symptoms and imaging findings do not coincide, secondary tumors should be considered in addition to infection as a diagnosis. In these cases, multiple pathological tissue biopsies should be performed.

Coccidioides immitis

Several case reports have studied caspofungin, with differing results. Caspofungin 50 mg/day following administration of amphotericin B in a patient with acute pulmonary coccidioidomycosis who had undergone transplantation showed promising results. In a patient with disseminated coccidioidomycosis, first-line therapy with amphotericin B and caspofungin alone failed to elicit a response, but the patient was then given caspofungin combined with fluconazole, with good results. A published report described a patient with disseminated and meningeal coccidioidomycosis in whom conventional therapy with fluconazole, voriconazole, and amphotericin B failed; caspofungin 50 mg/day after a loading dose of 70 mg intravenously was also unsuccessful.

[Invasive aspergillosis in the leukemic patient].

Invasive pulmonary aspergillosis (IPA) remains a life threatening complication in immuno-compromised and especially in neutropenic patients. We report our experience in the diagnosis and therapeutic management of IPA in 8 patients with acute leukemia. All patients were neutropenic (PNN < 100/mm3, mean duration = 37 days) when IPA was diagnosed. Clinical signs included fever above 39 degrees and cough in all cases, chest pain in 4 cases, hemoptysis in 3 cases, rales in 5 cases. Chest x ray showed one lesion in 4 cases and multiple lesions in 4 cases. The diagnosis of IPA was established by bronchoalveolar lavage (BAL) in 5 cases, tissue biopsy in one case, positive sputum in one case and it was highly probable in one case. Thoracic computed tomographic (CT) scans were preformed after diagnosis confirmation of IPA and showed one or multiple lesions with air crescent signs. Serological tests were positive in 4 cases late in the course of IPA. All patients were treated with i.v. Amphotericin B. Outcome was favorable in 5 cases and three patients died by massive hemoptysis (in two cases) and systemic aspergillosis (in one case). Early diagnosis and appropriate treatment are essential to improve IPA prognosis.

Recommendation of Antimicrobial Dosing Optimization During Continuous Renal Replacement Therapy.

Continuous Renal Replacement Therapy (CRRT) is more and more widely used in patients for various indications recent years. It is still intricate for clinicians to decide a suitable empiric antimicrobial dosing for patients receiving CRRT. Inappropriate doses of antimicrobial agents may lead to treatment failure or drug resistance of pathogens. CRRT factors, patient individual conditions and drug pharmacokinetics/pharmacodynamics are the main elements effecting the antimicrobial dosing adjustment. With the development of CRRT techniques, some antimicrobial dosing recommendations in earlier studies were no longer appropriate for clinical use now. Here, we reviewed the literatures involving in new progresses of antimicrobial dosages, and complied the updated empirical dosing strategies based on CRRT modalities and effluent flow rates. The following antimicrobial agents were included for review: flucloxacillin, piperacillin/tazobactam, ceftriaxone, ceftazidime/avibactam, cefepime, ceftolozane/tazobactam, sulbactam, meropenem, imipenem, panipenem, biapenem, ertapenem, doripenem, amikacin, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, azithromycin, tigecycline, polymyxin B, colistin, vancomycin, teicoplanin, linezolid, daptomycin, sulfamethoxazole/trimethoprim, fluconazole, voriconazole, posaconzole, caspofungin, micafungin, amphotericin B, acyclovir, ganciclovir, oseltamivir, and peramivir.

Invasive pulmonary aspergillosis in acute leukemia: characteristic findings on CT, the CT halo sign, and the role of CT in early diagnosis.

Invasive pulmonary aspergillosis (IPA) in immunocompromised patients is often difficult to diagnose. Many pathogens present initially with similar, nonspecific pulmonary findings. Air crescent formation has been reported to be highly suggestive of IPA in the appropriate clinical setting, but this is a late sign in an otherwise rapidly fatal infection. The authors reviewed the available chest computed tomography (CT) scans of nine patients with acute leukemia and documented IPA, including four patients with serial scans obtained during the course of infection. Typical CT findings of IPA were multiple inflammatory nodules, often with one large dominant mass, or a single peripheral masslike infiltrate. Cavitation or air crescent formation occurred late in the course of infection, usually at the time of bone marrow recovery from chemotherapy. CT scans obtained early in the course of infection in two patients demonstrated a distinctive feature of one or more pulmonary masslike infiltrates surrounded by a halo of low attenuation. These lesions subsequently progressed to cavitation or air crescent formation typical of IPA. While this CT halo sign may not be pathognomonic for Aspergillus, seen in the appropriate host, it may suggest early on the possibility of IPA.

[A case of coccidioidomycosis in Turkey imported from the United States of America].

Coccidioidomycosis caused by Coccidioides immitis or Coccidioides posadasii is a rare infectious disease except in endemic regions. In this report the third documented imported case of coccidioidomycosis in Turkey was presented. A thirty-year-old male patient was admitted to our hospital with fever and purulent drainage from his chest tube. He had worked in Arizona, USA, until 4 months before this presentation. While in Arizona, he experienced cough and hemoptysis and was diagnosed as pulmonary coccidioidomycosis. He was treated with itraconazole for two months and he had no symptoms for 3 years. He then returned to Turkey and 2 months after his return to Turkey, he was admitted to another hospital in Istanbul with dyspnea and diagnosed as hydro-pneumothorax, and pleural fluid obtained from the inserted chest tube was found to be purulent. One gram of BID amoxicillin-clavulanate was given. Physical examination on admission revealed a purulent drainage on the right side chest tube, a temperature of 38.5°C and decreased breath sounds on the right lung. Piperacillin-tazobactam 3 x 4.5 g intravenous and fluconazole 400 mg intravenous once daily were started. Human immunodeficiency virus test was negative. Gram-negative diplococci and rods, gram-positive cocci and septate hyphae were seen in the Gram stain of his pleural fluid. Pleural fluid culture revealed Moraxella catarrhalis after 24 hours incubation and a mold after 72 hours of incubation. Anti-coccidioidal antibodies were found positive in a titer of 1/2. Hydro-pneumothorax, atelectasis and a 3 mm nodules in the right lung were seen in his thorax CT. The patient's pleural fluid and the culture plates were sent to the Public Health Institute of Turkey, Mycology Reference Laboratory (PHIT-MRL), with a clinical suspicion of coccidioidomycosis. The specimen and plates were submitted to the PHIT-MRL Bio Safety Level-3 laboratory for mycological evaluation. The microscopic examination of 15% KOH preparations of pleural fluid specimens revealed septate hyphae which appear to be in the early stages of forming arthroconidia. The pleural fluid culture grew buff-white coloured colonies with aerial hyphae, which were suspected of being a Coccidioides spp. The strain was identified as C.immitis/posadasii by direct microscopy and culture, and subsequently confirmed by the FDA-approved DNA probe. DNA sequence analysis of the ITS and D1/D2 rDNA regions confirmed the isolate to be C.posadasii species [ITS 100% match to GenBank Accession No. AB232901 (630/630 base pair match), and D1/D2 100% match to GenBank Accession No. AB232884 (617/617 base pair match)]. ITS1 and ITS2 barcode analysis also confirmed the species to be C.posadasii, which is the species endemic in Arizona. Susceptibility testing was performed according to Clinical and Laboratory Standards Institute M38-A2 guidelines in the Fungus Testing Laboratory of the University of Texas Health Science Center at San Antonio and minimal inhibitory concentration values were; 0.125 µg/ml for amphotericin B, posaconazole and voriconazole, 0.5 µg/ml for itraconazole and 8 µg/ml for fluconazole. He had decortication of the pleura and was discharged from hospital after six weeks treatment with intravenous fluconazole which was continued orally for one year. Anti-coccidioidal antibodies were negative after two months of treatment. The patient is currently asymptomatic. The presented case is the third case reported from Turkey and provides additional contribution to the existing literature with regard to the appearance of arthroconidium, which is the unusual hyphal form, instead of the expected spherules in the infected tissue.

[Diagnosis and therapy of abscess forming pneumonia].

Aspiration of oro-pharyngeal secretions and gastric content is the most frequent cause of formation of primary lung abscess. A compromised mental status (e.g. alcoholism, sedatives, stroke) and esophageal dysfunction (e.g. herniation, vomiting) are important risk factors. Aspiration pneumonia presents as a subacute disease and is usually not distinguishable from other causes of pneumonia, until typical radiological signs of cavitation and putrid sputum appear 8 to 14 days after the initial event of aspiration. Anaerobic bacteria play a pivotal role in an almost exclusively mixed spectrum of causative organisms. Aerobic pathogens are also frequently isolated, but whether they are an active part of infection or merely represent colonizers remains unclear in many instances. Differential diagnosis includes bronchial neoplasms, either as necrotizing carcinoma or as the cause of poststenotic cavernous pneumonia, other infectious diseases like tuberculosis, Pneumocystis carinii pneumonia or endocarditis with septic metastases, and lung artery embolism or vasculitis (M. Wegener). Fiberoptic bronchoscopy is extremely helpful in determining cause and etiology of the disease and should be carried out in all patients presenting with cavernous lung lesions. Bacteriological sampling should be performed using protected specimen brushing (PSB) technique. Broncho-alveolar lavage might serve as a less expensive but also less sensitive alternative measure. Since anaerobic bacteria resemble ubiquitous commensals of the oral cavity, sputum is of no use in anaerobic culture. Principal therapeutic strategy is antibiotic therapy for an extended period, usually four weeks to four months, unless radiologic changes and as well laboratory as clinical indicators of infection are completely resolved. Clindamycin, optionally supplemented with a second or third generation cephalosporin and Ampicillin/Sulbactam proved equally effective in treating aspiration pneumonia and primary lung abscess. The role of Moxifloxacin and other new flouroquinolones with their favorable pharmacodynamics is currently evaluated. Provided that antibiotics are prescribed for a sufficient period of time and patients' compliance is ensured, surgical procedures are limited to a negligible number of complications, e.g. recurrent severe hemoptysis, empyema or broncho-pleural fistula.

Coccidioides immitis

In very severe cases, combination therapy with amphotericin B and an azole have been postulated, although no trials have been conducted. Caspofungin in combination with fluconazole has been cited as beneficial in a case report of a 31-year-old Asian patient with coccidioidal pneumonia. In a case report of a 23-year-old Black male with HIV and coccidioidal meningitis, combination therapy of amphotericin B and posaconazole led to clinical improvement. Posaconazole has been approved by the European Commission as a salvage therapy for refractory coccidioidomycosis. Clinical trials are now ongoing for further evaluation. Voriconazole is also being studied in salvage therapy for refractory cases. A case report indicated that voriconazole in combination with amphotericin B as salvage therapy for disseminated coccidioidomycosis was successful.

Anaerobic infection

Empiric antibiotic therapy for health care-associated intra-abdominal should be driven by local microbiologic results. Empiric coverage of likely pathogens may require multidrug regimens that include agents with expanded spectra of activity against gram-negative aerobic and facultative bacilli. These include meropenem, imipenem-cilastatin, doripenem, piperacillin-tazobactam, or ceftazidime or cefepime in combination with metronidazole. Aminoglycosides or colistin may be required. Antimicrobial regimens for children include an aminoglycoside-based regimen, a carbapenem (imipenem, meropenem, or ertapenem), a beta-lactam/beta-lactamase-inhibitor combination (piperacillin-tazobactam or ticarcillin-clavulanate), or an advanced-generation cephalosporin (cefotaxime, ceftriaxone, ceftazidime, or cefepime) with metronidazole.

[Pneumonia in patients with chronic lymphocytic leukemia. Study of 30 episodes].

To analyse the etiology, diagnostic methods and response to therapy in 30 episodes of pneumonia diagnosed in 17 patients with chronic lymphocytic leukemia (CLL) between 1995 and 2000. In each episode of pneumonia the following data were analysed: age, gender, treatment of CLL, antiinfectious prophylaxis, granulocytopenia, CD4/CD8 lymphocytes ratio, hipogammaglobulinemia, origin of pneumonia (nosocomial or community-acquired), localisation, respiratory insufficiency, need for mechanical ventilation, antimicrobial therapy and response. Diagnostic methods included blood and sputum cultures, fiberoptic bronchoscopy and search for antigens in urine (Legionella pneumophila serogroup 1, galactomannan, and Streptococcus pneumoniae). Median age of the series was 60 yr. (range 50-86) and 12 patients were male. Chlorambucil and prednisone were used in 13 cases and fludarabine in 8. Granulocytopenia was present in 14 episodes, hypogammaglobulinemia was seen in 22 and CD4/CD8 ratio was lower than 1 in 8 out of 14 evaluable cases. Etiology of pneumonia was established in 16 episodes (53%). Fiberoptic bronchoscopy was the most useful technique (83% of positive diagnoses) followed by blood cultures (38%). Two patients were diagnosed of aspergillosis at autopsy. Pneumococcus was the most frequent agent (5 cases) followed by Pseudomonas aeruginosa (4), Pneumocystis carinii (2) and Aspergillus fumigatus (2). One out of the two patients with P. carinii pneumonia had received fludarabin and the remaining was treated with prednisone for long time. Ten patients (30%) had died: P. aeruginosa (3 cases), P. carinii (2), A. fumigatus (2), Mycobacterium xenopi (1), and unknown microorganism (2). In this series of CLL patients the frequency of etiologic diagnosis of pneumonias was good. Pneumococcus was the most frequent microorganism. Pneumonias caused by opportunistic microorganisms were associated to the treatment with fludarabin or prednisone and were associated to a high mortality rate.

Cancer

A low-carbohydrate diet (ketogenic diet) has been sometimes been recommended as a supportive therapy for cancer treatment. Diagnosis Most cancers are initially recognized either because of the appearance of signs or symptoms or through screening. Neither of these leads to a definitive diagnosis, which requires the examination of a tissue sample by a pathologist. People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, (contrast) CT scans and endoscopy. The tissue diagnosis from the biopsy indicates the type of cell that is proliferating, its histological grade, genetic abnormalities and other features. Together, this information is useful to evaluate the prognosis and to choose the best treatment.

First_Aid_Step2

CSF analysis is not necessary and may precipitate a herniation syndrome. Lab values may show peripheral leukocytosis, ↑ ESR, and ↑ CRP. Initiate broad-spectrum IV antibiotics and surgical drainage (aspiration or excision) if necessary for diagnostic and/or therapeutic purposes. Lesions < 2 cm can often be treated medically. Administer a third-generation cephalosporin + metronidazole +/– vancomycin; give IV therapy for 6–8 weeks followed by 2–3 weeks PO. Obtain serial CT/MRIs to follow resolution. Dexamethasone with taper may be used in severe cases to ↓ cerebral edema; IV mannitol may be used to ↓ ICP. CNS lymphoma, toxoplasmosis, or PML P. jiroveci pneumonia or recurrent bacterial pneumonia A retrovirus that targets and destroys CD4+ T lymphocytes. Infection is characterized by a progressively high rate of viral replication that leads to a progressive decline in CD4+ count (see Figure 2.8-6).

[Invasive aspergillosis in hematooncological patients: advantages and disadvantages of various diagnostic methods, treatment options and financial costs of therapy].

Invasive aspergillosis (IA) is a leading invasive fungal infection in hematooncological patients. The aim of this study was to analyse the incidence, diagnostic procedures and treatment of IA in hematooncological department in large hospital in the Czech Republic. A retrospective analysis of medical and laboratory records from patients hospitalised in our department with proven/probable IA between January 2000 and December 2006 was performed. 52 cases of IA in 51 patients were identified (17.3% proven IA/82.7% probable IA). Number of IA cases notably increased during study period (1 case of IA in 2000 vs 21 cases of IA in 2006) and majority of them was of nosocomial origin (61.5%). Pulmonary aspergillosis was diagnosed in 46 cases (88.5%). Patients treated for acute leukemia or undergoing allogeneic stem cell transplantation represent the group at the highest risk of IA (in total 52% of cases). Fever and signs of pulmonary involvement were the most common clinical signs of infection (presented in 92.3% and 69.2 cases respectively). Conventional diagnostic methods including autopsy were able to diagnose only 15 cases of IA (28.8%). In all other cases (71.2%) the diagnosis was done by detection of galactomannan (GM) in serum. Introduction of GM monitoring enabled erlier initiation of antifungal treatment by 4 days. Initial therapy of IA led to the treatment response (partial and complete) in 18 (34.6%) of infections--the highest percentage of response has been seen in voriconazole monotherapy group (42%) and when combination of voriconazole and caspofungin has been used (83%). Salvage therapy was initiated due to the failure of initial treatment in 21 (40.3%) of cases. Patients were treated mostly with combination ofvoriconazole and caspofungin and/or monotherapy with voriconazole has been used with treatment response 55% and 50% respectively. Introduction of new antifungal drugs together with increased number of patients with IA led to the marked increase of total costs spent on treatment of IA per year--from 11,5 thousands CZK in 2000 to 6,2 millions CZK in 2006. IA is the most frequent cause of infection-related mortality in patients with haematological malignancies. Routine use of non-culture base methods in diagnosis of IA together with treatment using new, effective antifungals can improve prognosis of patients with this life threatening infection.

Ventilator-associated pneumonia

Risk factors for infection with an MDR strain include ventilation for more than five days, recent hospitalization (last 90 days), residence in a nursing home, treatment in a hemodialysis clinic, and prior antibiotic use (last 90 days). Possible empirical therapy combinations include (but are not limited to): vancomycin/linezolid and ciprofloxacin, cefepime and gentamicin/amikacin/tobramycin vancomycin/linezolid and ceftazidime Ureidopenicillin plus β-lactamase inhibitor such as piperacillin/tazobactam or ticarcillin/clavulanate a carbapenem (e.g., imipenem or meropenem) Therapy is typically changed once the causative bacteria are known and continued until symptoms resolve (often 7 to 14 days). For patients with VAP not caused by nonfermenting Gram-negative bacilli (like Acinetobacter, Pseudomonas aeruginosa) the available evidence seems to support the use of short-course antimicrobial treatments (< or =10 days).

[Treatment of pneumonia under hospital conditions].

A random sample of 24 patients affected by bacterial pneumonia has been investigated whether their illness is treated etiologically. The agents have been detected from the endoscopically obtained samples of blood or chest punctate (percutaneous needle aspirate--PNA) and their sensitivity to antibacterial drugs, used in our institution, have been investigated. The obtained results have been compared to the empirically applied drugs. In only three patients the first given drug corresponded to the later obtained finding of the agent's sensitivity and in one patient third and the fourth drug has been adequate. The rational initial therapy has been proposed on the basis of investigation of the sensitivity of the bacterial pneumonia agents.

Rates and appropriateness of antimicrobial prescribing at an academic children's hospital, 2007-2010.

Antimicrobial use in hospitalized children has not been well described. To identify targets for antimicrobial stewardship interventions, we retrospectively examined pediatric utilization rates for 48 antimicrobials from 2007 to 2010 as well as appropriateness of vancomycin and cefepime use in 2010. All children hospitalized between 2007 and 2010 at the Mayo Clinic Children's Hospital, a 120-bed facility within a larger adult hospital in Rochester, Minnesota. We calculated antimicrobial utilization rates in days of therapy per 1,000 patient-days. Details of vancomycin and cefepime use in 2010 were abstracted by chart review. Two pediatric infectious disease physicians independently assessed appropriateness of antibiotic use. From 2007 to 2010, 9,880 of 17,242 (57%) hospitalized children received 1 or more antimicrobials. Antimicrobials (days of therapy per 1,000 patient-days) used most frequently in 2010 were cefazolin (97.8), vancomycin (97.1), fluconazole (76.4), piperacillin-tazobactam (70.7), and cefepime (67.6). Utilization rates increased significantly from 2007 to 2010 for 10 antimicrobials, including vancomycin, fluconazole, piperacillin-tazobactam, cefepime, trimethoprim-sulfamethoxazole, caspofungin, and cefotaxime. In 2010, inappropriate use of vancomycin and cefepime was greater in the pediatric intensive care unit than ward (vancomycin: 17.8% vs 6.4%, P = .001; cefepime: 9.2% vs 3.9%, P = .142) and on surgical versus medical services (vancomycin: 20.5% vs 8.0%, P = .001; cefepime: 19.4% vs 3.4%, P ≤ .001). The most common reason for inappropriate antibiotic use was failure to discontinue or de-escalate therapy. In our children's hospital, use of 10 antimicrobials increased during the study period. Inappropriate use of vancomycin and cefepime was greatest on the critical care and surgical services, largely as a result of failure to de-escalate therapy, suggesting targets for future antimicrobial stewardship interventions.

Pneumonias acquired from others. 2. Radiographic findings, treatment.

Although patterns found on the chest film of a patient suspected to have pneumonia are usually nonspecific by themselves, they are useful in eliminating or narrowing diagnostic possibilities. For example, a miliary pattern suggests miliary tuberculosis, but it may also be caused by several noninfectious diseases (table 1). Other clues, such as the presence or absence of fever, must also be considered to arrive at a likely diagnosis. Cavitary lesions, bilateral hilar adenopathy, pleural effusions, and pulmonary nodules are other findings that are commonly seen on the chest film of these patients. Possible infectious and noninfectious causes are listed in tables 2 through 5. Antimicrobial therapy that is appropriate, free from side effects, and cost-effective must be chosen. The frequency of administration of a drug can make a great difference in the total cost of treatment, since hospitals charge for each intravenous dose. The clinician should consider which drug is effective against the infective organism and also the least expensive to administer (table 6).

Cytomegalovirus pneumonia in an immunosuppressed sarcoidosis patient; a rare case of cytomegalovirus infection in a sarcoidosis patient.

Sarcoidosis is a multisystemic granulomatosis disease that is mostly treated with immunosuppressive regimens. Studies demonstrated that these patients are prone to develop various infections. However, some infections including viral severe pneumonia is rare complications in sarcoidosis patients. In the present report, we described for cytomegalovirus (CMV) pneumonia in a female patient with sarcoidosis which has been successfully managed by ganciclovir. Herein, we present a known case of sarcoidosis admitted to the emergency department because of fever, dyspnea, and productive cough. The patient was receiving prednisolone and methotrexate for months. The primary chest x-ray imaging revealed bilateral infiltration, especially in the upper lobes and hilar lymphadenopathy. The lung high resolution computed tomography showed a bilateral diffuse nodular pattern. After 72 hours of antimicrobial treatment, the fever was still present and the patient became a candidate for fiberoptic bronchoscopy. The gram staining of the bronchial fluid, polymerase chain reaction for tuberculosis, and PCP was also unremarkable. However, the PCR-CMV was positive. The quantitative PCR for CMV form blood sample was taken and the result came back as 3.6*10<sup3</sup. With the impression of CMV pneumonia, a daily dose of 5mg of ganciclovir was prescribed. After 3 weeks of receiving 5mg/kg of ganciclovir twice daily (600mg daily), clinical symptoms, and dyspnea improved. Also, the radiological findings improved. In the present report, we demonstrated that sarcoidosis patients' receiving immunosuppressives are prone to develop CMV pneumonia, and fever and dyspnea were the alarm signs of CMV pneumonia is our patient which was successfully managed by ganciclovir.

[Rapid development of multiple meniscal signs complicating invasive pulmonary aspergillosis in a patient receiving chemotherapy for acute leukemia].

This report describes the rapid development of multiple meniscal signs complicating invasive pulmonary aspergillosis in a 53-year-old man receiving chemotherapy for acute leukemia. While undergoing first induction therapy for AML, he developed chest pain, and multiple bilateral infiltrations were seen in chest roentgenograms. Administration of antibiotics, antifungal agents, steroid pulse therapy and G-CSF was begun. Pulmonary cavities with meniscal signs developed. The next day, pneumothorax and hemothorax were noted. Although drainage and mechanical ventilation were performed, the patient died after massive hemoptysis. Invasive pulmonary aspergillosis was diagnosed at autopsy.

Pulmonary capillary hemangiomatosis

Diagnosis Lung biopsy is essential to make this diagnosis. This can be difficult if the pulmonary pressure is high. Investigations Chest X ray may show enlargement of the heart and ill-defined patchy lesions in the lung fields. CT chest typically shows wide spread ill-defined centrilobular nodules of ground glass opacity. This is a nonspecific finding and may be seen in a number of pulmonary diseases. CT pulmonary angiography usually shows enlargement of the main pulmonary artery. When measured by echocardiography or pulmonary angiography, the pulmonary arterial pressure is typically elevated. Differential diagnosis Pulmonary veno-occlusive disease Associations This condition has been reported in patients with Ehlers Danlos syndrome, CREST syndrome and scimitar syndrome. Treatment The only definitive treatment for this condition currently is lung transplantation. Median survival without treatment is 3 years. Imatinib may be of use.

Disseminated cutaneous Fusarium moniliforme infections in a leukemic child.

A 5-year-old boy had a 10-month remission of acute lymphocytic leukemia (ALL) after chemotherapy. Re-induction chemotherapy was performed for relapse of ALL. Thereafter, he suffered from an episode of neutropenic fever with pneumonia. One week following control of the condition with antibiotics, a 1 x 1-cm, red, painful nodule appeared on the left thigh, which was initially suspected to be Pseudomonas infection. Parenteral ceftazidime and amikacin were administered, but persistent high fever, mild cough, and a few painful erythematous papulonodules on the face and lower extremities appeared several days later (Fig. 1). These lesions increased insidiously in diameter up to 2-5 cm with central necrosis. Hemogram showed neutropenia with a shift to the left [white blood cell (WBC) count, 2.1 x 10(9)/L; neutrophil count, 0.21 x 10(9)/L]. A skin biopsy showed heavy growth of hyaline branching septate hyphae in the deep dermis and subcutis, together with fat necrosis (Fig. 2). Invasion of molds into vessels and sweat glands was also seen. A culture from a lesion yielded Fusarium moniliforme, but no fungi were isolated from blood specimens. Only mild infiltrations on bilateral lower lung fields were detected by chest roentgenography. The skin lesions gradually healed and the fever subsided 2 weeks after the initiation of therapy with amphotericin B 30 mg and itraconazole 200 mg daily. Meanwhile, relapse of leukemia was detected by hemogram showing atypical leukocytosis (WBC count of 24,400 x 10(9)/L, with blast cells representing 78%). A course of chemotherapy with cytarabine, mitoxantrone, and VP-16 was prescribed, subsequently resulting in neutropenia (WBC count, < 0.1 x 10(9)/L; neutrophil count, 0/L) and spiking fever. Although the aforementioned antifungal therapy was continued, the centers of the originally healed lesions turned dusky red, swollen, necrotic, and ulcerative. There were more than 10 such ecthymiform lesions. After administration for 22 days, itraconazole was discontinued because of no appreciable effects. Granulocyte colony-stimulating factor (G-CSF) salvage was used, and the neutropenia gradually subsided 20 days later. In addition, the ecthymiform lesions gradually resolved. Amphotericin B was discontinued 1 week following neutrophil recovery. The patient died of Acinetobacter baumannii and Stenotrophomonas maltophilia sepsis 8 months later.

Galactomannan does not precede major signs on a pulmonary computerized tomographic scan suggestive of invasive aspergillosis in patients with hematological malignancies.

Detection of serum galactomannan (GM) antigen and presence of the halo sign on a pulmonary computerized tomographic (CT) scan have a high specificity but a low sensitivity to diagnose invasive aspergillosis (IA) in patients at risk for this disease. To our knowledge, the relationship between the time at which pulmonary infiltrates are detected by CT and the time at which GM antigens are detected by enzyme immunoassay (EIA) has not been studied. In a prospective study, tests for detection of GM were performed twice weekly for patients with hematological malignancies who had undergone hematopoetic stem cell transplantation (HSCT) or had received induction and/or consolidation chemotherapy. A pulmonary CT scan was performed once weekly. Infiltrates were defined as either major or minor signs. IA was classified as proven, probable, or possible, in accordance with the definition stated by the European Organization for Research and Treatment of Cancer-Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. We analyzed 161 episodes of infection in 107 patients (65 allogeneic HSCT recipients, 30 autologous HSCT recipients, and 66 induction and/or consolidation chemotherapy recipients). A total of 109 episodes with no IA, 32 episodes with possible IA, and 20 episodes with probable or proven IA were identified. Minor pulmonary signs were detected by CT in 70 episodes (43%), and major pulmonary signs were detected by CT in 11 episodes (7%). Univariate and multivariate analyses revealed no significant association between detection of GM by EIA and detection of abnormal pulmonary signs by CT. A significant association was found between GM levels and receipt of piperacillin-tazobactam. GM test results were not positive before major signs were seen on CT images. Only 7 (10%) of 70 patients with minor pulmonary signs had positive GM test results before detection of the greatest pathologic change by CT. We show that detection of GM by EIA does not precede detection of major lesions by pulmonary CT. In the clinical setting, the decision to administer mold-active treatment should based on detection of new pulmonary infiltrates on CT performed early during infection, rather than on results of EIA for detection of GM.