Inflammation and infection in stable coronary disease and acute coronary syndrome

OBJECTIVE: To study whether inflammation and infection are related to coronary artery disease. DESIGN: Sixty patients (44 males, mean age 62 +/- 13 years) with acute coronary syndrome and 40 with stable coronary artery disease (31 males, age 64 +/- 10 years) and a control group of 40 individuals (34 males, 53 +/- 5 years) were analyzed. IgG against Chlamydia pneumoniae, Cytomegalovirus and Helicobacter pylori plus C-reactive protein were assessed in all serum samples. In addition, IgM against C. pneumoniae and Cytomegalovirus on admission and C-reactive protein one month later were measured in acute patients. RESULTS: No IgM seropositivity was observed. A high prevalence of IgG seropositivity with no significant differences among the groups was found: C. pneumoniae: acute group 44 (73%), stable group 29 (73%) and control group 25 (63%); Cytomegalovirus: 55 (92%), 37 (92%) and 38 (95%), respectively; and H. pylori, 43 (72%), 32 (80%) and 34 (85%) respectively. There was a high rate of positive C-reactive protein in the acute group: 48 (80%) vs 10 (25%) the stable group and 0% the control group (p < 0.001). C-reactive protein levels were higher in Q-wave infarction than in unstable angina/ non-Q-wave infarction (median 22.65 vs 7.69, p < 0.001). One month later, C-reactive protein levels decreased (median 22.65 vs 3.38, p < 0.001), but were still positive in 40%. CONCLUSIONS: These data suggest that inflammation is detected by the commonly used methods in clinic practice in acute coronary syndromes and to a lesser extent in stable coronary artery disease. It seems that different mechanisms other than infection account for this inflammatory response, at least this being so when infection is assessed by serology. Serology does not appear to be an adequate method to determine the possible relationship among coronary syndromes, infection and inflammation.     

Treatment options in emerging mold infections

Although Zygomycetes, Fusarium spp, and Scedosporium spp are far less frequent causes of invasive fungal disease than Aspergillus and Candida, they are emerging. These types of infections in severely immunocompromised patients have a common feature: a poor clinical response to antifungal therapy. Infection is usually airborne, although local infections in cases of skin trauma are also possible. These fungi are resistant to some common antifungal agents; therefore, surgical debridement of the necrotic tissue, when possible, should be combined with specific systemic antifungal treatment in immunocompromised patients. In the absence of randomized clinical trials, most experience in the treatment of these infections is with amphotericin B. Experience with new antifungal agents is still limited, and recovery from neutropenia remains the main predictor of a favorable outcome.     

Listeriosis in patients infected with human immunodeficiency virus

Although resistance to Listeria monocytogenes infection requires intact T cell-mediated immunity, only 20 patients with human immunodeficiency virus (HIV) infection and listeriosis (including one patient described herein) have been reported to date. Listeriosis developed before AIDS in five cases. Syndromes included meningitis in nine cases, bacteremia in nine, brain abscess in one, and endocarditis in one. Eighteen patients were treated with ampicillin, penicillin, or amoxicillin with or without aminoglycosides. Clinical and microbiologic responses were obtained in one patient with bacteremia treated with vancomycin and in one patient with meningitis treated with trimethoprim-sulfamethoxazole. Three of the nine patients with meningitis died, as did the patient with brain abscess. All nine patients with bacteremia and the patient with endocarditis survived. No case of relapse was documented. L. monocytogenes, although uncommon, should be considered in the differential diagnosis of febrile illness, meningitis, and brain abscess in patients with HIV infection.     

Clostridium difficile Isolates with High Linezolid MICs Harbor the Multiresistance Gene cfr

We studied the molecular mechanisms of linezolid resistance in 9 isolates of toxigenic Clostridium difficile with high linezolid MICs. The activity of linezolid was determined against 891 clinical isolates of toxigenic C. difficile. The MIC₅₀ and MIC₉₀ of linezolid were 0.75 μg/ml and 1.5 μg/ml, respectively. Nine strains (1%) showed high linezolid MICs (6 μg/ml to 16 μg/ml) and also were resistant to clindamycin, erythromycin, and chloramphenicol. These strains were selected for molecular studies: sequencing of domain V of the 23 rRNA gene, detection of the cfr methyltransferase gene, and sequencing of the ribosomal protein genes rplC and rplD. Molecular relatedness between strains was assessed using PCR ribotyping and MLVA (multilocus variable-number tandem-repeat analysis) typing. The strains belonged to ribotypes 001 (2/9), 017 (6/9), and 078 (1/9). MLVA showed that strains of ribotype 001 and 017 belonged to the same clonal complex in each ribotype. We did not detect mutations in the 23S rRNA gene. The cfr gene was detected in 7 of 9 strains. Sequencing of cfr amplicons revealed a similarity of 100% to a fragment of transposon Tn6218 of C. difficile, which was annotated as a putative chloramphenicol/florfenicol resistance protein. We were unable to detect mechanisms of resistance to linezolid in the 2 strains belonging to ribotype 001. While the relevance of our results lies in the detection of the cfr gene as a possible mechanism of resistance to linezolid in C. difficile, our findings should be assessed by further investigations to characterize these possible cfr genes and their contribution to linezolid resistance.     

A multicenter multinational study of abdominal candidiasis: epidemiology,outcomes and predictors of mortality

Purpose

Clinical data on patients with intra-abdominal candidiasis (IAC) is still scarce.

Methods

We collected data from 13 hospitals in Italy, Spain, Brazil, and Greece over a 3-year period (2011–2013) including patients from ICU, medical, and surgical wards.

Results

A total of 481 patients were included in the study. Of these, 27 % were hospitalized in ICU. Mean age was 63 years and 57 % of patients were male. IAC mainly consisted of secondary peritonitis (41 %) and abdominal abscesses (30 %); 68 (14 %) cases were also candidemic and 331 (69 %) had concomitant bacterial infections. The most commonly isolated Candida species were C. albicans (n = 308 isolates, 64 %) and C. glabrata (n = 76, 16 %). Antifungal treatment included echinocandins (64 %), azoles (32 %), and amphotericin B (4 %). Septic shock was documented in 40.5 % of patients. Overall 30-day hospital mortality was 27 % with 38.9 % mortality in ICU. Multivariate logistic regression showed that age (OR 1.05, 95 % CI 1.03–1.07, P < 0.001), increments in 1-point APACHE II scores (OR 1.05, 95 % CI 1.01–1.08, P = 0.028), secondary peritonitis (OR 1.72, 95 % CI 1.02–2.89, P = 0.019), septic shock (OR 3.29, 95 % CI 1.88–5.86, P < 0.001), and absence of adequate abdominal source control (OR 3.35, 95 % CI 2.01–5.63, P < 0.001) were associated with mortality. In patients with septic shock, absence of source control correlated with mortality rates above 60 % irrespective of administration of an adequate antifungal therapy.

Conclusions

Low percentages of concomitant candidemia and high mortality rates are documented in IAC. In patients presenting with septic shock, source control is fundamental.

     

Klebsiella and enterobacter: antibiotic resistance and treatment implications

KLEBSIELLA: spp. and Enterobacter spp. are widespread throughout the environment and also carried by humans. Both genera are well-recognized community and nosocomial pathogens and cause significant infections. They are a common cause of respiratory and nonrespiratory infections. Klebsiella spp. is responsible for 1% to 5% of all cases of community-acquired pneumonia and between 0% to 23% of those acquired in the hospital, and its frequency is greater in alcoholic patients. The majority of cases are unilateral in the posterior segment of the right upper lobe. Lung abscess can occur after a pneumonic process or secondarily to Klebsiella spp. infections and have high rates of morbidity and mortality. K. pneumoniae is one of the most common microorganisms responsible for empyema. Klebsiella spp. and Enterobacter spp. rank fourth and third, respectively, as causes of hospital-acquired pneumonia mainly in patients during the early period of mechanical ventilation. Klebsiella spp. are intrinsically resistant to penicillins and can acquire resistance to third- and fourth-generation cephalosporins owing to the production of plasmid-mediated extended-spectrum beta-lactamases (ESBLs). These plasmids frequently carry aminoglycoside-modifying enzymes. Enterobacter spp. are intrinsically resistant to ampicillin, amoxicillin, amoxicillin-clavulanate, first-generation cephalosporins, and cefoxitin owing to the production of constitutive AmpC beta-lactamase. The derepression of this enzyme is increasingly frequent among clinical isolates and confers resistance to third-generation cephalosporins, and ureido- and carboxypenicillins; fourth-generation cephalosporins retain reasonable activity against depressed strains. Most isolates of Klebsiella spp. and Enterobacter spp. are susceptible to fluoroquinolones, trimethoprimsulfamethoxazole, aminoglycosides, and carbapenems. In some instances, treatment of severe infections caused by these microorganisms may benefit from the combination of beta-lactams (or fluoroquinolones) with aminoglycosides. Because of the high risk for developing resistance during treatment, all severe infections should be carefully watched during therapy.     

Visceral leishmaniasis in patients infected with human immunodeficiency virus (HIV)

In an 8-month period nine patients with human immunodeficiency virus (HIV) infection were diagnosed as having visceral leishmaniasis; all diagnoses were based on cultures (eight from bone marrow and one from the skin). Visceral leishmaniasis developed before full-blown acquired immunodeficiency syndrome (AIDS) in seven patients and at the same time as or after AIDS in the other two patients. Three patients had a history of leishmaniasis. Clinical manifestations and laboratory findings were atypical. Leishmania species were cultured from samples taken from all patients; however, six patients had an insignificant antileishmanial antibody titer and Leishmania amastigotes were not seen in their bone marrow smears. Four isolates were identified by isoenzyme analysis as Leishmania donovani infantum. Five patients died, including two patients who had completed at least one 3-week course of therapy with N-methylglucamine antimoniate. Screening should be done for visceral leishmaniasis in patients with HIV infection who live or travel in areas where the disease is endemic. The diagnosis of visceral leishmaniasis may frequently be missed if cultures are not done.