KPC-producing Klebsiella pneumoniae, finally targeting Turkey.

We report here the first identification of the worldwide spread of Klebsiella pneumoniae carbapenemase-2-producing and carbapenem-resistant K. pneumoniae clone ST258 in Turkey, a country where the distantly-related carbapenemase OXA-48 is known to be endemic. Worryingly, this isolate was also resistant to colistin, now considered to be the last-resort antibiotic for carbapenem-resistant isolates.

Use of quantitative antibiogram analysis to determine the clonality of coagulase-negative Staphylococcus species from blood culture.

Two phenotypic methods, quantitative antibiogram analysis and colony morphology, were compared to pulsed-field gel electrophoresis (PFGE) for distinguishing the clonality of coagulase-negative Staphylococcus (CNS) species. The results of these three methods were correlated with the patients' clinical findings for 23 episodes in which CNS species were isolated from two blood culture bottles within a 24-h period. Quantitative antibiogram and colony morphology at 24 h correlated with PFGE typing in 21 (91%) and 20 (87%) episodes, respectively. All episodes associated with CNS strains with identical PFGE patterns had quantitative antibiogram similarity coefficients < 10, whereas most episodes associated with strains with different PFGE patterns had quantitative antibiogram similarity coefficients >or= 17. The CNS isolate pairs were less likely to be associated with infection if the strains had different PFGE types or a quantitative antibiogram similarity coefficient >or= 17. Clinical microbiology laboratories should consider use of the quantitative antibiogram similarity coefficient to aid clinicians in distinguishing infection-associated CNS blood isolates from contaminants.

[Diagnosis of Clostridium difficile diarrhea: in search of a more efficient clinical focus]. / Diagnóstico de diarrea por Clostridium difficile: en busca de un enfoque clínico más eficiente.

BACKGROUND: The clinical parameters for the suspicion of Clostridium difficile infections, namely the use of antimicrobials and diarrhea, have a low predictive value for the diagnosis. AIM: To search other clinical variables and determine a clinical prediction model for (Clostridium difficile diarrhea. PATIENTS AND METHODS: All patients to whom a Clostridium difficile study was requested, were prospectively studied during 5 months. Clinical variables of these patients were registered. The diagnosis of Clostridium difficile was done using the cytotoxicity test in fibroblast cultures. RESULTS: Ninety two patients were analyzed and in 26, the diagnosis of Clostridium difficile was confirmed. A logistic regression model disclosed an age over 60 years old, the presence of mucus in the stools and a temperature over 37.8 degrees C in the previous 24 h, as significant predictors of the infection. The correlation of the model, between the predicted probability and the observed condition, was 81.5%. CONCLUSIONS: The presence of the clinical variables identified in this study are associated with a high probability of an infection by Clostridium difficile in patients with diarrhea and the recent use of antimicrobials.

[Infection of ascending aortic graft: treatment with surgical cleaning, graft preservation and transposition of muscle flaps. Report of two cases]. / Infección de prótesis de aorta ascendente: tratamiento con aseo quirúrgico, preservación de prótesis y transposición de colgajo muscular en dos casos.

Mediastinitis with graft infection is a serious complication of ascending aorta replacement. We report two cases of graft infection, treated with surgical cleaning, graft preservation and transposition of muscle flaps. A 62 years old male was admitted 34 days after an ascending aortic grafting due to a sternal dehiscence and mediastinitis. Antimicrobial treatment was started and a surgical cleaning performed, leaving an open sternotomy. Three days later, the thoracic cavity was closed with a rectus abdominis muscle flap. After 23 months of follow up, the patient is well and without evidence of infection. A 74 years old male was subjected to an aortic valve and ascending aorta replacement and a myocardial revascularization. In the postoperative period, the patient developed septic signs, and a purulent drainage. A CAT scan showed a liquid collection surrounding the aortic graft. On tW Sixteenth postoperative day, a surgical cleaning was performed and the thorax was closed with the pectoralis major muscle. After 10 months of follow up, the patient is in Good condition and without evidence of infection.

[Infective endocarditis: short and long-term results in 261 cases managed by a multidisciplinary approach]. / Endocarditis infecciosa: análisis de 261 casos y resultados del tratamiento con un enfoque multidisciplinario.

BACKGROUND: Early diagnosis, an effective treatment and prompt recognition of complications are essential to improve the prognosis of infective endocarditis (IE). AIM: To report the results of a multidisciplinary approach to diagnosis and management of patients with IE at the Universidad Católica de Chile Hospital. PATIENTS AND METHODS: The clinical history, diagnosis, treatment and outcome of 261 episodes (Duke criteria) of IE admitted between January 1980 and January 1999 were analyzed. These included 185 episodes of native, 73 of prosthetic valve and 3 of nonvalvular IE. RESULTS: Sixty nine percent of patients were men and the mean age was 49 +/- 16 years. Seventy five percent had a definite diagnosis of IE (Duke). S. viridans, staphylococci and enterococci together constituted 85% of the isolated bacterial strains. Twenty seven had culture-negative IE, related to a high incidence of antibiotic therapy prior to diagnosis. Transesophageal echocardiography was performed in 102 cases and it detected vegetations in 91% of aortic and 96% of mitral IE, rupture or prosthesis dehiscence in 67% of aortic and 52% of mitral IE and abscesses in 51% of aortic and 15% of mitral IE. Fifty one percent developed heart failure and 34% had embolic events. S. aureus IE was associated to a higher incidence of embolic events, complications which contraindicated surgery and increased mortality rate (27%). Of all patients, 40% were treated exclusively with antibiotics, 52% were operated on and 8% had surgical indication but were nonoperable because of serious complications. The overall mortality was 16.3%: 13% in the medical, 9% in the surgical and 81% in the non-operable groups. The type of treatment and mortality rates did not differ between IE of native valves and prosthetic valves. Long term follow up showed survival rates of 73% at 5 years and 66% at 10 years. CONCLUSION: A multidisciplinary approach may be very helpful to improve the prognosis of IE.

Outbreak of Stenotrophomonas maltophilia bacteremia in allogenic bone marrow transplant patients: role of severe neutropenia and mucositis.

From March 1997 through November 1997, 8 allogenic bone marrow transplant (BMT) patients developed Stenotrophomonas maltophilia bacteremia on the hematology service at UCLA Medical Center (Los Angeles). Five of these patients had undergone transplantation during the same hospitalization that S. maltophilia bacteremia was detected (case patients). Compared with 7 concurrently hospitalized allogenic BMT patients (control patients), the 5 case patients were more likely to have been hospitalized in room A (P=.045), to have severe neutropenia on the culture date (P=.028), to have a longer duration of severe neutropenia (P=.05), to have severe mucositis (P=. 028), and to have received total parenteral nutrition (P=.028). Pulsed-field gel electrophoresis revealed that 2 of 3 isolates from case patients hospitalized in room A were identical. In allogenic BMT patients, severe neutropenia and severe mucositis may promote infection with S. maltophilia by impairing host defenses.

A multistate nosocomial outbreak of Ralstonia pickettii colonization associated with an intrinsically contaminated respiratory care solution.

From 1 February through 30 April 1998, 4 hospitals reported a total of 34 patients colonized with Ralstonia pickettii. All but 1 had been exposed to 0.9% saline solution manufactured by 1 company (Modudose; Kendall, Mainsfield, MA), which was used during endotracheal suctioning. Culture of saline solution from previously unopened vials yielded R. pickettii. All available product and patient isolates were genotypically related by pulsed-field gel electrophoresis (PFGE) analysis. The contaminated saline solution was manufactured at the same plant that had been associated with a similar outbreak in 1983. The 1983 and 1998 R. pickettii isolates were unrelated, as determined by PFGE. In both 1983 and 1998, a 0. 2-microm cartridge filter was used for terminal sterilization. The detection of R. pickettii should alert hospital personnel to the possibility of product contamination. In this outbreak, prompt notification of public health agencies resulted in rapid notification of other health care providers, which likely prevented additional outbreaks.

Adverse drug reactions (ADRs) in patients with HIV infection. A prospective study.

AIM: A prospective drug surveillance method was used to monitor 50 ambulatory patients with HIV infection, who were controlled in the Sexual Transmission Disease Service at Dr. Sotero del Río Hospital (Santiago, Chile). The aim of this work was to characterize and study the frequency, characteristics, and associated factors of the ADRs in HIV-infected patients. PATIENTS AND METHODS: Patients were interrogated once or twice a month by a clinical pharmacist, who consigned data concerning the drug prescribed by the physician, drug-related signs and symptoms, and the laboratory's parameters as renal, hepatic, hematological function, and biochemical test. The ADR probability was assessed for an algorithm. RESULTS: The frequency of adverse drug reactions found in the group of patients studied was 32.0%. The dermatological, hepatic, and hematological systems were the most affected by adverse drug reactions. Trimethroprim-sulfamethoxazole and zidovudine were the drugs mainly associated with ADRs. Patients with lymphocytes CD4+ count of 200 or less, presented a higher frequency of ADRs. 48.5% of ADRs were classified as probable. Severe reactions were found in 18.5% of the patients, and moderate in 70.4%. 50% of patients with ADRs needed the withdrawal of the implicated drug, and an 18.5% dose decreased. 63% of the ADRs were dose-independent. CONCLUSION: There was a higher frequency of ADRs in those patients with multiple-drug therapy, but the frequency of ADR was not associated with age, gender, or hematological test.

Time course of antibody response to tetanus toxoid and pneumococcal capsular polysaccharides in patients infected with HIV.

The temporal course of the humoral immune response to T-cell-dependent and T-cell-independent type 2 antigens was evaluated in HIV-infected patients. In all, 26 seropositive patients were vaccinated with tetanus toxoid and 23-valent pneumococcal vaccines; total IgG and IgG1 antibodies to tetanus toxoid (Ttox) and total IgG and IgG2 antibodies against 23 Streptococcus pneumoniae capsular antigens (PPS) were measured at baseline, 2 months, and 12 months after vaccination. For the Ttox, baseline levels of IgG1 (Ttox-IgG1) increased from 11.0 to 19.5 mg/L at 2 months postimmunization. Overall only 6 patients (23%) showed a significant response. At 12 months postvaccination, Ttox-IgG and T-tox-IgG1 were significantly lower than baseline levels (Ttox IgG basal; 11.0 mg/L, 12 months; 0.8 mg/L, Ttox IgG1 baseline; 13.1 mg/L, Ttox IgG1 12 months; 2.4 mg/L) and in 10 patients, antibodies that fell below protective levels (0.6 mg/L). In contrast with PPS, a significant response was observed at 2 and 12 months (PPS-IgG basal; 35.9 U/ml, 2 months; 151.4 U/ml, 12 months; 59.7 U/ml; PPS-IgG2 baseline 20.3 U/ml, 2 months; 113.2 U/ml, 12 months; 51.9 U/ml). Overall, 19 patients (76%) showed an immune response to pneumococcal polysaccharides antigens. Immunization with the Ttox T-cell-dependent antigen fails to elicit a significant immune response and may induce inhibition of antibody production in HIV-infected patients. In contrast, immunization with a T-cell-independent type 2 antigen can cause the pneumococcal polysaccharides to induce significant immune response in a high proportion of HIV-infected patients.

PIP: The temporal course of the humoral response to T-cell-dependent and T-cell-independent type 2 antigens was evaluated in HIV-infected patients. 26 HIV-seropositive patients were vaccinated with tetanus toxoid and 23-valent pneumococcal vaccines; total IgG and IgG1 antibodies to tetanus toxoid (Ttox) and total IgG and IgG2 antibodies against 23 Streptococcus pneumoniae capsular antigens (PPS) were measured at baseline, 2 months, and 12 months after vaccination. For the Ttox, baseline levels of IgG1 (Ttox-IgG1) increased from 11.0 to 19.5 mg/L at 2 months postimmunization. Overall, 6 patients (23%) showed a significant response. At 12 months postvaccination, Ttox-IgG and Ttox-IgG1 were significantly lower than baseline levels, and in 10 patients, antibodies fell below protective levels. In contrast with PPS, a significant response was observed at 2 and 12 months. Overall, 19 patients (76%) showed an immune response to pneumococcal polysaccharide antigens. Immunization with the Ttox T-cell-dependent antigen elicits no significant immune response and may induce inhibition of antibody production in HIV-infected patients. In contrast, immunization with a T-cell-independent type 2 antigen can cause the pneumococcal polysaccharides to induce significant immune response in a high proportion of HIV-infected patients.

Critical evaluation of 4-week incubation for fungal cultures: is the fourth week useful?

To determine the benefit of a 4-week incubation for mycology cultures, we evaluated all positive cultures during the fourth week of incubation in a 1-year period. Of 3,855 positive mycology cultures (yeast, 82%; molds, 18%), 62 (1.6%) were positive during the fourth week (yeast, 42%; molds, 58%). Only 15 of the 62 cultures (24%) were considered clinically relevant (2 isolates from invasive fungal infection and 13 isolates from cutaneous mycosis). With the exception of those from skin samples, isolates recovered during the fourth week are rarely important for patient care.

[Resistance of human immunodeficiency virus (HIV) to zidovudine. Genotypic analysis in strains isolated from Chilean patients]. / Resistencia del virus de inmunodeficiencia humano (VIH) a zidovudina (AZT): análisis genotípico en cepas aisladas de pacientes chilenos.

BACKGROUND: Resistance of HIV to AZT is the result of mutations in the pol gene that codifies the enzyme reverse transcriptase. AIM: To assess the resistance to antiretroviral drugs in Chilean patients infected with HIV. MATERIAL AND METHODS: The presence of mutations was searched in 22 patients infected with HIV. The emergence or persistence of these mutations was studied in sequential samples of 19 patients. The presence of the mutation that confers resistance to didanosine (DDI) was studied in those subjects exposed to the drug. Polymerase chain reaction techniques were used to analyze mutations in codons 41, 70 and 215 of the pol gene (resistance to AZT) and the mutation in codon 71 (resistance to DDI). RESULTS: On admission, none of the patients without previous exposure to AZT had drug resistance mutations. Seven of 12 patients (58.3%) that had received AZT had mutations in codon 215. In two, they were associated to a mutation in codon 41 and in two, a mutation in codon 70. After a mean follow up of 14 months, 13 of 15 patients (86%) that received AZT had viral strains genotypically resistant to the drug. In nine of these, the resistance was associated with disease progression. None of the 10 patients that received DDI had the mutation in codon 74 that confers resistance to the drug. However, in one of these patients, that never received AZT, a virus with a mutation in codon 215 was detected. CONCLUSIONS: A high percentage of patients that have received monotherapy with AZT have genotypic resistance to the drug. This resistance is associated with clinical and immunological derangement in 70% of these subjects.

Something's rotten: a nosocomial outbreak of malodorous Pseudomonas aeruginosa.

From July 1994 through November 1996, a phenotypically unique strain of Pseudomonas aeruginosa producing a pungent, "rotten-potato" odor and a positive lysine decarboxylase reaction was isolated from 39 patients at UCLA Medical Center (Los Angeles). Most cases (95%) were in intensive care units and had clinical infections (72%). Most isolates (74%) were recovered from cultures of respiratory secretions. To determine risk factors for acquisition of the organism, 23 cases were compared with 23 randomly selected controls matched by service and isolate date. Multivariate analysis revealed that isolation of malodorous P. aeruginosa was associated with mechanical ventilation of > 24 hours' duration (odds ratio [OR] = 9.4; P = .001) and transfer from an outside hospital (OR = 5.7; P = .04). DNA from outbreak strains hybridized to P. aeruginosa-specific toxin A and phospholipase C gene probes and all outbreak isolates tested were found to be identical by use of pulsed-field gel electrophoresis. An unusual phenotypic characteristic of the strain led to the recognition of a nosocomial outbreak of P. aeruginosa infection associated with mechanical ventilation.

Antiphospholipid syndrome associated with cytomegalovirus infection: case report and review.

Antiphospholipid antibodies are commonly related to connective tissue disorders, the use of certain drugs, and infection. It is thought that antiphospholipid syndrome (APS) is associated primarily with connective tissue disorders. We describe a healthy young male who had an episode of APS that was associated with cytomegalovirus infection and who developed mesenteric and femoropopliteal thrombosis. He responded well to treatment with anticoagulants; 6 months after the onset of APS, IgM and IgG anticardiolipin antibody titers declined. We point out the importance of screening for infectious agents in cases of APS; if the agents are identified, APS may be transitory.

[Natural history of human immunodeficiency virus infection in a cohort of Chilean patients]. / Historia natural de la infección por virus de inmunodeficiencia humano en una cohorte de pacientes chilenos.

We characterized clinical manifestations and the risk to develop AIDS in a cohort of 32 patients infected with human immunodeficiency virus without AIDS A multivariate analysis was performed to determine association between the progression of infection and control variables (socioeconomic level, age, sex and sexual preferences) and causal variables (psycho-social changes, significant clinical events, stress scoring and sexual activity). The cumulative AIDS incidence, defined as a CD4 lymphocyte count below 200 cells/cm3 was 50% at 6.5 years and 82% at 8 years. Using clinical criteria to define AIDS, 50% developed the disease at 8 years of follow up. Among studied factors, only age (faster progression at higher age) and time of evolution were associated with progression in stages before AIDS, the most frequent diseases were acute diarrhea, sexual transmission diseases, oral candidiasis, sinusitis and varicella zoster infections. The reduction; of CD4 lymphocytes-below 200 cells/cm3 always preceded the symptoms of the disease. Two patients have remained more than eight years without clinical or immunological deterioration.

PIP: Clinical manifestations and the risk of developing AIDS were studied in a cohort of 32 HIV-seropositive patients referred by their treating physicians to the Center for Medical Investigation of the Catholic University of Chile. The only exclusion criteria were a CD4 lymphocyte count below 400 or marked symptoms of AIDS. The study design included an examination at entry and every 6 months thereafter for a maximum follow up of 3 years. A multivariate analysis was conducted to determine the relation between disease progression and control and causal variables. The subjects were 8 women averaging 38 years old and 24 men averaging 33 years. Most were middle class and had higher education. 46% of the men became sexually active before age 15 and 42% were homosexual. HIV transmission was sexual in 28 subjects, through intravenous drug use in 2, and by unknown route in 2. The subjects had been infected for an average of 4.3 years at entry into the study. Of the 30 whose date of infection was known, 16 developed AIDS during the study according to the criterion of CD4 lymphocyte count below 200, and 8 of these developed markers of AIDS. 50% of patients developed AIDS 6.5 years after infection and 82% 8 years after. Using clinical criteria, 50% of patients had developed AIDS 8 years after infection. Multivariate analysis showed only subject's age at infection (faster progression at higher ages) and length of time since infection to be related to the risk of developing AIDS. No association was observed between development of the disease and sex, sexual orientation, use of alcohol or drugs, smoking, history of sexually transmitted diseases, number of sexual partners, or frequency of sexual relations. The most frequently observed pathologies before the stage of AIDS were acute diarrhea, sexually transmitted diseases, oral candidiasis, sinusitis, and varicela zoster infections. In the patients who progressed to AIDS, the decline of the CD4 lymphocyte count below 200 always preceded other symptoms. Two patients showed no significant decline in CD4 lymphocyte count or clinical manifestations of AIDS more than 8 years after infection.

Pharmacokinetics of vancomycin in patients with severely impaired renal function.

The pharmacokinetics of 1 g dose of intravenous vancomycin was studied in 8 patients with severe renal failure. Serum vancomycin levels were determined by fluorescence polarization immunoassay. After single dose of vancomycin peak concentrations ranged from 37.8 microg.ml-1 to 109.3 microg.ml-1 (mean 64.9 +/- 21.7 microg.ml-1). Vancomycin trough concentration 168h after administration of the antibiotic ranged from 2.23 microg.ml-1 to 11.42 microg.ml-1 (mean 6.55 +/- 2.8 microg.ml-1). The data were analyzed using a PCNONLINE computer program, and in all patients a triexponential model described how concentrations decreased in time. Three-compartment parameters obtained from the 8 patients were t1/2 alpha = 0.312 +/- 0.242 h, t1/2 beta 6.012 +/- 5.36 h, and t1/2 gamma = 131.0 +/- 46.7 h. Vd = 0.158 +/- 0.121 1.kg-1, Vdss = 0.920 +/- 0.248 1.kg-1 and total Cl = 0.10 +/- 0.049 1.h-1 per kg of weight. Between 1.5% and 21.2% of the administered vancomycin dose was eliminated during hemodialysis. The dialysis clearance of vancomycin ranged from 50.6 ml.min-1 to 76.8 ml.min-1 (average: 62.4 +/- 10.4 ml.min-1. However, after dialysis plasma concentrations returned to pre-dialysis values. In accordance to our kinetic study 1 g of vancomycin given every 7 days is adequate treatment for methicillin-resistant Staphylococcus aureus infections in patients with severe renal failure whose creatinine clearance is lower than 10 ml.min-1.