George L. Daikos

An outbreak of tuberculosis caused by multiple-drug-resistant tubercle bacilli among patients with HIV infection

OBJECTIVE To evaluate a nosocomial outbreak of tuberculosis caused by multiple-drug-resistant bacilli among patients with tuberculosis and HIV infection. DESIGN A case-control study. PATIENTS Patients with HIV infection and culture-proven tuberculosis. MEASUREMENTS Patient characteristics, date of diagnoses of HIV infection and disease, date of diagnosis of tuberculosis, Mycobacterium tuberculosis susceptibility results, and medical center contact. RESULTS Sixty-two patients who had tuberculosis caused by multiple-drug-resistant bacilli (cases) and 55 patients who had tuberculosis caused by susceptible or single-drug-resistant bacilli (controls) were identified. Controls were more likely to be black (odds ratio, 0.4; 95% CI, 0.2 to 0.9) or Haitian (odds ratio, 0.2; CI, 0.1 to 0.6) compared with cases, who were more likely to be homosexual men (odds ratio, 2.9; CI, 1.3 to 6.4). Forty-four cases (71%) had previous contact with an HIV clinic compared with 15 controls (27%) (P less than 0.0001). Cases were more likely to have had AIDS (odds ratio, 7.7; CI, 1.5 to 53.7), to have been hospitalized on an HIV ward (odds ratio, 8.3; CI, 2.3 to 29.7), to have been seen in an HIV clinic (odds ratio, 7.8; CI, 3.4 to 18.1), to have received intravenous therapy in an HIV clinic (odds ratio, 13.0; CI, 4.6 to 37.0), or to have received inhalation pentamidine in an HIV clinic before a diagnosis of tuberculosis was made. Multiple logistic regression analysis showed that a diagnosis of AIDS (odds ratio, 11.2; CI, 3.1 to 40.6) and HIV clinic visits (odds ratio, 13.0; CI, 2.7 to 63.7) before a diagnosis of tuberculosis were significantly associated with tuberculosis caused by multiple-drug-resistant bacilli. Using susceptibility patterns and appointment dates, we found that 22 cases had previous contact with a person who had tuberculosis caused by multiple-drug-resistant bacilli in the HIV clinic. CONCLUSIONS Nosocomial transmission of M. tuberculosis from other HIV-infected patients with tuberculosis caused by multiple-drug-resistant bacilli can occur. These findings have serious public health implications and demand strict adherence to acid-fast bacilli isolation precautions.

Clinical Presentation and Outcome of Patients with HIV Infection and Tuberculosis Caused by Multiple-Drug-resistant Bacilli

OBJECTIVE To determine the clinical manifestations of patients with human immunodeficiency virus (HIV) infection and tuberculosis caused by multiple-drug-resistant bacilli compared with those with single-drug-resistant or susceptible bacilli. DESIGN Descriptive, case-control, and cohort studies. SETTING A large urban teaching hospital. PATIENTS Sixty-two patients with tuberculosis caused by multiple-drug-resistant bacilli (cases) and 55 patients with tuberculosis caused by single-drug-resistant or susceptible bacilli (controls). MEASUREMENTS Characteristics of clinical presentation, radiographs, pathologic abnormalities, antituberculosis treatment, and clinical course. RESULTS Twenty cases (32%) had concomitant pulmonary and extrapulmonary disease at presentation compared with 9 controls (16%; odds ratio, 2.4; 95% CI, 1.0 to 5.9). More cases had alveolar infiltrates (76%; odds ratio, 3.6; CI, 1.2 to 11.4), interstitial infiltrates with a reticular pattern (67%; odds ratio, 7.8; CI, 1.0 to 83.5), and cavitations (18%; odds ratio, 6.6; CI, 0.8 to 315.3) on initial chest radiographs compared with controls (49%, 19%, and 3%, respectively). Pathologic specimens from cases showed extensive necrosis, poor granuloma formation, marked inflammatory changes with a predominance of neutrophils, and abundant acid-fast bacilli. Twenty-five cases received two or more effective antituberculosis drugs for more than 2 months. Only 2 cases had three consecutive negative cultures for Mycobacterium tuberculosis; one patient died within 1 day of the last negative culture, and the other had positive cultures 496 days later. The remaining 23 cases had persistently or intermittently positive cultures despite therapy. The clinical course of these cases suggested overwhelming miliary tuberculosis with involvement of the lungs (77%), pleura (15%), stool (34%), meninges (13%), bone marrow (16%), blood (10%), lymph nodes (10%), and skin (8%). The median survival time was 2.1 months for cases compared with 14.6 months for controls (P = 0.001, log-rank test). CONCLUSIONS Tuberculosis caused by multiple-drug-resistant bacilli in patients with HIV infection is associated with widely disseminated disease, poor treatment response with an inability to eradicate the organism, and substantial mortality.

Prospective observational study of the impact of VIM-1 metallo-β-lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections.

ABSTRACT VIM-1-producing Klebsiella pneumoniae (VPKP) is an emerging pathogen. A prospective observational study was conducted to evaluate the importance of VIM production on outcome of patients with K. pneumoniae bloodstream infections (BSIs). Consecutive patients with K. pneumoniae BSIs were identified and followed up until patient discharge or death. A total of 162 patients were included in the analysis; 67 (41.4%) were infected with VPKP, and 95 were infected with non-VPKP. Fourteen of the patients infected with VPKP were carbapenem resistant (Carbr) (MIC > 4 μg/ml), whereas none of the non-VPKP exhibited carbapenem resistance. The patients infected with a Carbr organism were more likely (odds ratio, 4.08; 95% confidence interval [CI], 1.29 to 12.85; P = 0.02) to receive inappropriate empirical therapy. The all-cause 14-day mortality rates were 15.8% (15 of 95) for patients infected with VIM-negative organisms, 18.9% (10 of 53) for those infected with VIM-positive carbapenem-susceptible organisms, and 42.9% (6 of 14) for those infected with VIM-positive Carbr organisms (P = 0.044). In Cox regression analysis, age (hazard ratio [HR], 1.03; 95% CI, 1.01 to 1.06; P = 0.021), rapidly fatal underlying disease (HR, 2.84; 95% CI, 1.26 to 6.39; P = 0.012), and carbapenem resistance (HR, 2.83; 95% CI, 1.08 to 7.41; P = 0.035) were independent predictors of death. After adjustment for inappropriate empirical or definitive therapy, the effect of carbapenem resistance on outcome was reduced to a level of nonsignificance. In patients with K. pneumoniae BSIs, carbapenem resistance, advanced, age, and severity of underlying disease were independent predictors of outcome, whereas VIM production had no effect on mortality. The higher mortality associated with carbapenem resistance was probably mediated by the failure to provide effective therapy.

Two Doses of a Lipid Formulation of Amphotericin B for the Treatment of Mediterranean Visceral Leishmaniasis

To evaluate the efficacy of a short course of a lipid formulation of amphotericin B (L-AmB) for the treatment of Mediterranean visceral leishmaniasis (VL), an open prospective study was conducted. Forty-one children with parasitologically confirmed leishmaniasis received L-AmB, 10 mg/kg daily for 2 days. The comparison groups were 30 children who, in a previous study, were treated with L-AmB, 4 mg/kg daily for 5 days, and 52 children who were treated with meglumine antimoniate. At 6 months after completion of treatment, overall treatment success was noted for 40 of 41 children treated with 2 doses of L-AmB, 27 of 30 children treated with 5 doses of L-AmB, and 47 of 52 children treated with meglumine antimoniate. Abatement of fever, reduction in spleen size, and correction of laboratory parameters occurred more quickly among the children who received 2 doses of L-AmB than among the comparison groups, and the total estimated cost of the 2-dose regimen was also lower than that of the other regimens. Two doses of L-AmB, 10 mg/kg each, is cost-effective therapy for Mediterranean VL in children.

Activity of Plazomicin (ACHN-490) against MDR clinical isolates of Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. from Athens, Greece

Abstract The in vitro activity of plazomicin was evaluated against 300 multidrug resistant (MDR) (carbapenemase and/or ESBL-producing) isolates from four hospitals in Athens, an area where carbapenemase-producing organisms are endemic. Most of the isolates were also resistant to the legacy aminoglycosides with the MIC50/MIC90 to tobramycin, amikacin and gentamicin being 32/>32, 32/>32 and 4/>8 μg/ml, respectively. ACHN-490 retained activity (MICs⩽4 μg/ml) against all isolates of Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. tested with MIC50 and MIC90 of 1 and 2 μg/ml, respectively, irrespective of their MDR phenotype and it represents a promising alternative for the treatment of the most problematic Gram-negative pathogens.

Mother to child transmission of hepatitis C virus: Rate of infection and risk factors

To determine the rate of mother-to-child transmission of hepatitis C virus (HCV) and identify risk factors associated with HCV transmission we prospectively studied 86 infants born to anti-HCV positive mothers. HCV infection was verified in all mothers before delivery and their HCV viral load was measured at or near delivery using reverse transcription polymerase reaction. For HCV genotyping the INNO-LiPA II probe assay was used. All mothers were tested for HIV infection. Possible risk factors for vertical transmission were recorded. The children were followed up for a minimum of 18 months for evidence of HCV infection, as determined by persistent HCV antibodies, or detection of HCV-RNA. Vertical transmission was restricted to infants born to viraemic mothers and the rate was 3.6% (95% CI 0.004–0.123). The HIV-infected mothers and those using drugs intravenously were more likely to transmit HCV to their children. The infected children had the same genotype as their mothers. Although the HCV RNA titre was higher in mothers who transmitted the virus than in those who did not, the viral load had borderline significance (p=0.08). Viral transmission was not influenced by mothers age, mode of delivery, genotype or type of feeding. Mother-to-child transmission of hepatitis C virus is uncommon and restricted to infants born to HCV viraemic mothers. Active drug use and HIV coinfection increase the risk for HCV vertical transmission.

Disseminated Miliary Tuberculosis of the Skin in Patients with AIDS: Report of Four Cases

We present clinical, bacteriologic, and pathological findings for four patients with AIDS and cutaneous miliary tuberculosis. All patients had generalized tuberculosis with hematogenous dissemination to multiple organs including the skin. Microscopic examination of the skin lesions revealed ill-formed or no granulomata, extensive necrosis, and numerous acid-fast bacilli. Mycobacterium tuberculosis was detected in the skin lesions by cultures for three patients and by polymerase chain reaction for one. Three of the isolates were resistant to at least isoniazid and rifampin, and one was susceptible to these drugs. The outcome was rapidly fatal for the three patients with multidrug-resistant tuberculosis. This report draws attention to the reappearance of a once-rare manifestation of disseminated tuberculosis which, in the setting of advanced human immunodeficiency virus disease, may offer the first indication of infection with multidrug-resistant M. tuberculosis and a poor prognosis.

Wilson disease in children: analysis of 57 cases.

Objectives: Wilson disease (WD) has a wide spectrum of clinical manifestations. Affected children may be entirely asymptomatic and the diagnosis problematic. Herein we present the clinical and laboratory characteristics of 57 children with WD and point out the diagnostic difficulties in a pediatric population. Patients and Methods: Clinical and laboratory data were collected from 57 consecutive children with WD. Evaluation included detailed physical examination, conventional laboratory testing, genetic analysis, and liver biopsy. Results: The mean age at diagnosis was 9.27 ± 3.62 years (range 4 months–18 years). Twenty patients were symptomatic, 19 were referred because of abnormal liver function test results and/or hepatomegaly, and 18 received their diagnoses after family screening. Twenty-two patients had both Kayser-Fleischer ring and decreased serum ceruloplasmin levels, 13 had urinary copper excretion after penicillamine challenge >1600 μg/24 hours, and 3 had liver copper content >250 μg/g dry weight. Of the remaining 19 patients, 17 had both low serum ceruloplasmin ≤20 mg/dL and increased urinary copper excretion, >75 μg/24 hours before, or >1000 μg/24 hours after penicillamine challenge. In 2 patients with equivocal cases who had serum ceruloplasmin 26 mg/dL, the diagnosis was confirmed by genetic analysis. No correlation was found between specific mutations and the disease phenotypic expression. Chelating therapy was well tolerated, and the outcome was satisfactory. Conclusions: WD in children may be obscure and requires extensive investigation to establish the diagnosis. Genetic analysis is needed in equivocal cases.

The Evolution of Helicobacter Pylori Antibiotics Resistance Over 10 Years in Greece

Background: Increasingly, over time, antibiotic resistance is considered a problem for the efficacy of H. pylori eradication treatment. The aim of our study was to evaluate the changes in clarithromycin and levofloxacin resistance of H. pylori strains in Greek patients in two different time periods (in 2000 and in 2010). Methods: Gastric biopsies of consecutive H. pylori-positive patients were investigated retrospectively. Mutations in H. pylori 23S rRNA and gyrA genes associated with resistance to clarithromycin and quinolones, respectively, were determined by allelic specific polymerase chain reaction. Results: In the first time period (2000), H. pylori resistance patterns were evaluated in 50 and in the second period (2010) in 57 patients. During the first time period 30 and 0% of patients were infected with clarithromycin- or quinolone-resistant strains, respectively. In the second time period (2010), the percentage of patients infected with clarythromycin or quinolone resistance strains increased to 42 and 5.3%, respectively. Conclusions: Our study showed an increase in the prevalence of both clarithromycin and quinolones resistance of H. pylori. Although the resistance rate to quinolones increased over the years, it is relatively low justifying its use for the eradication of H. pylori infections.

Enterobacteriaceae Bloodstream Infections: Presence of Integrons, Risk Factors, and Outcome

ABSTRACT A prospective observational study was conducted to identify factors associated with bloodstream infections (BSIs) caused by integron-carrying Enterobacteriaceae and to evaluate the clinical significance of integron carriage. Consecutive patients with Enterobacteriaceae BSIs were identified and followed up until discharge or death. Identification of blood isolates and susceptibility testing were performed by the Wider I automated system. int-1-specific PCR, conserved-segment PCR, and DNA sequencing were used to determine the presence, length, and content of integrons. The relatedness among the isolates was examined by pulsed-field gel electrophoresis. Two hundred fifty episodes of Enterobacteriaceae BSI occurred in 233 patients; 109 (43.6%) were nosocomial, 82 (32.8%) were community acquired, and 59 (23.6%) were health care associated. Integrons were detected in 11 (13.4%) community-acquired, 24 (40.7%) health care-associated, and 46 (42.2%) nosocomial isolates. Integron-carrying organisms were more likely to exhibit resistance to three or more classes of antimicrobials (odds ratio [OR], 9.84; 95% confidence interval [95% CI], 5.31 to 18.23; P < 0.001) or to produce extended-spectrum β-lactamases (OR, 5.75; 95% CI, 2.38 to 13.89; P < 0.001) or a VIM-type metallo-β-lactamase (P, 0.003). Inter- or intraspecies integron transfer and cross-transmission of integron-carrying clones were observed. Use of cotrimoxazole (OR, 4.77; 95% CI, 1.81 to 12.54; P < 0.001) and a nosocomial or other health care setting (OR, 3.07; 95% CI, 1.30 to 7.22; P, 0.01) were independently associated with BSIs caused by integron-carrying Enterobacteriaceae. Patients with a nonurinary source of bacteremia (OR, 9.46; 95% CI, 2.77 to 32.32; P < 0.001) and a Pitt bacteremia score of ≥4 (OR, 23.36; 95% CI, 7.97 to 68.44; P < 0.001) had a significantly higher 14-day mortality rate, whereas integron carriage did not affect clinical outcomes. These findings may have implications affecting antibiotic policies and infection control measures.