Management of infections due to KPC-producing Klebsiella pneumoniae

The emergence of the Klebsiella pneumoniae carbapenemases in K. pneumoniae and other Gram-negative bacteria, usually on a background of multidrug resistance, has led to difficult therapeutic choices. Among available antibiotics, tigecycline and the polymyxins are the most frequently active against these organisms in vitro. Optimal therapy of infections due to these bacteria may involve maximization of antibiotic dose as well as their use in combination

Combination therapy of disseminated coccidioidomycosis with caspofungin and fluconazole

BACKGROUND: The current recommended therapy for diffuse coccidioidal pneumonia involves initial treatment with amphotericin B deoxycholate or high-dose fluconazole, followed by an azole after clinical improvement. Amphotericin B is more frequently used as initial therapy if the patient's deterioration is rapid. CASE PRESENTATION: A 31-year-old Korean male with coccidioidomycosis presented to the hospital with miliary infiltrates on chest X-ray (CXR) and skin rash on the face and trunk. Initially, the patient did not respond to amphotericin B deoxycholate therapy. However, following caspofungin and fluconazole combination therapy, the patient showed favourable radiological, serological, and clinical response. CONCLUSION: This appears to be the first case of diffuse coccidioidal pneumonia with skin involvement in an immunocompetent patient who was treated successfully with caspofungin and fluconazole. Combination therapy with caspofungin and fluconazole may, therefore, be an alternative treatment for diffuse coccidioidal pneumonia that does not respond to amphotericin B deoxycholate therapy

Differential Activity of the Combination of Vancomycin and Amikacin on Planktonic vs. Biofilm-Growing Staphylococcus aureus Bacteria in a Hollow Fiber Infection Model

Combining currently available antibiotics to optimize their use is a promising strategy to reduce treatment failures against biofilm-associated infections. Nevertheless, most assays of such combinations have been performed in vitro on planktonic bacteria exposed to constant concentrations of antibiotics over only 24 h and the synergistic effects obtained under these conditions do not necessarily predict the behavior of chronic clinical infections associated with biofilms. To improve the predictivity of in vitro combination assays for bacterial biofilms, we first adapted a previously described Hollow-fiber (HF) infection model by allowing a Staphylococcus aureus biofilm to form before drug exposure. We then mimicked different concentration profiles of amikacin and vancomycin, similar to the free plasma concentration profiles that would be observed in patients treated daily over 5 days. We assessed the ability of the two drugs, alone or in combination, to reduce planktonic and biofilm-embedded bacterial populations, and to prevent the selection of resistance within these populations. Although neither amikacin nor vancomycin exhibited any bactericidal activity on S. aureus in monotherapy, the combination had a synergistic effect and significantly reduced the planktonic bacterial population by -3.0 to -6.0 log10 CFU/mL. In parallel, no obvious advantage of the combination, as compared to amikacin alone, was demonstrated on biofilm-embedded bacteria for which the addition of vancomycin to amikacin only conferred a further maximum reduction of 0.3 log10 CFU/mL. No resistance to vancomycin was ever found whereas a few bacteria less-susceptible to amikacin were systematically detected before treatment. These resistant bacteria, which were rapidly amplified by exposure to amikacin alone, could be maintained at a low level in the biofilm population and even suppressed in the planktonic population by adding vancomycin. In conclusion, by adapting the HF model, we were able to demonstrate the different bactericidal activities of the vancomycin and amikacin combination on planktonic and biofilm-embedded bacterial populations, suggesting that, for biofilm-associated infections, the efficacy of this combination would not be much greater than with amikacin monotherapy. However, adding vancomycin could reduce possible resistance to amikacin and provide a relevant strategy to prevent the selection of antibiotic-resistant bacteria during treatments

Community-associated Methicillin-resistant Staphylococcus aureus in Pediatric Patients

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections increased from 2000 to 2003 in hospitalized pediatric patients in Houston. CA-MRSA was associated with greater illness than was infection with methicillin-susceptible strains. Children with CA-MRSA were younger and mostly African American. Of MRSA isolates, 4.5% had the inducible macrolide-lincosamide-streptogramin B phenotype

Reemerging Leptospirosis, California

Leptospirosis is a reemerging infectious disease in California. Leptospirosis is the most widespread zoonosis throughout the world, though it is infrequently diagnosed in the continental United States. From 1982 to 2001, most reported California cases occurred in previously healthy young adult white men after recreational exposures to contaminated freshwater. We report five recent cases of human leptospirosis acquired in California, including the first documented common-source outbreak of human leptospirosis acquired in this state, and describe the subsequent environmental investigation. Salient features in the California cases include high fever with uniform renal impairment and mild hepatitis. Because leptospirosis can progress rapidly if untreated, this reemerging infection deserves consideration in febrile patients with a history of recreational freshwater exposure, even in states with a low reported incidence of infection

Serologic testing for symptomatic coccidioidomycosis in immunocompetent and immunosuppressed hosts

Serologic studies are an important diagnostic tool in the clinical evaluation and follow-up of persons with coccidioidomycosis. Numerous types of serologic tests are available, including immunodiffusion, enzyme immunoassay, and complement fixation. We conducted a retrospective review of the results of 1,797 serologic tests spanning 12 months from the onset of coccidioidomycosis in 298 immunocompetent and 62 immunosuppressed persons with symptomatic infection. Using the onset of symptoms as a reference point, we plotted the positive or negative serologic results over time for both groups. Compared with the immunocompetent group, immunosuppressed persons had lower rates of seropositivity for every type of test during the first year after onset of symptoms for coccidioidomycosis, although many results did not achieve statistical significance. Combining the results of these tests increased the sensitivity of the serologic evaluation in immunocompromised patients. Immunosuppressed persons have the ability to mount a serologic response to coccidioidomycosis, but in some circumstances, multiple methods may be required to improve detection

Direct Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry Improves Appropriateness of Antibiotic Treatment of Bacteremia

Matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) allows the identification of microorganisms directly from positive blood culture broths. Use of the MALDI-TOF MS for rapid identification of microorganisms from blood culture broths can reduce the turnaround time to identification and may lead to earlier appropriate treatment of bacteremia. During February and April 2010, direct MALDI-TOF MS was routinely performed on all positive blood cultures. During December 2009 and March 2010 no direct MALDI-TOF MS was used. Information on antibiotic therapy was collected from the hospital and intensive care units' information systems from all positive blood cultures during the study period. In total, 253 episodes of bacteremia were included of which 89 during the intervention period and 164 during the control period. Direct performance of MALDI-TOF MS on positive blood culture broths reduced the time till species identification by 28.8-h and was associated with an 11.3% increase in the proportion of patients receiving appropriate antibiotic treatment 24 hours after blood culture positivity (64.0% in the control period versus 75.3% in the intervention period (p0.01)). Routine implementation of this technique increased the proportion of patients on adequate antimicrobial treatment within 24 hours

Mononuclear ruthenium(ii) theranostic complexes that function as broad-spectrum antimicrobials in therapeutically resistant pathogens through interaction with DNA

Six luminescent, mononuclear ruthenium(II) complexes based on the tetrapyridophenazine (tpphz) and dipyridophenazine (dppz) ligands are reported. The therapeutic activities of the complexes against Gram-negative bacteria (E. coli, A. baumannii, P. aeruginosa) and Gram-positive bacteria (E. faecalis and S. aureus) including pathogenic multi- and pan-drug resistant strains were assessed. Estimated minimum inhibitory and bactericidal concentrations show the activity of the lead compound is comparable to ampicillin and oxacillin in therapeutically sensitive strains and this activity was retained in resistant strains. Unlike related dinuclear analogues the lead compound does not damage bacterial membranes but is still rapidly taken up by both Gram-positive and Gram-negative bacteria in a glucose independent manner. Direct imaging of the complexes through super-resolution nanoscopy and transmission electron microscopy reveals that once internalized the complexes' intracellular target for both Gram-negative and Gram-positive strains is bacterial DNA. Model toxicity screens showed the compound is non-toxic to Galleria mellonella even at exposure concentrations that are orders of magnitude higher than the bacterial MIC