Treatment Of Bloodstream Infections Research Articles

Klebsiella pneumoniae bloodstream infection: epidemiology and impact of inappropriate empirical therapy.

Multidrug resistance associated with extended-spectrum beta-lactamase (ESBL) and Klebsiella pneumoniae carbapenemase (KPC) among K. pneumoniae is endemic in southern Europe. We retrospectively analyzed the impact of resistance on the appropriateness of empirical therapy and treatment outcomes of K. pneumoniae bloodstream infections (BSIs) during a 2-year period at a 1420-bed tertiary-care teaching hospital in northern Italy. We identified 217 unique patient BSIs, including 92 (42%) KPC-positive, 49 (23%) ESBL-positive, and 1 (0.5%) metallo-beta-lactamase-positive isolates. Adequate empirical therapy was administered in 74% of infections caused by non-ESBL non-KPC strains, versus 33% of ESBL and 23% of KPC cases (p < 0.0001). To clarify the impact of resistance on BSI treatment outcomes, we compared several different models comprised of non-antibiotic treatment-related factors predictive of patients’ 30-day survival status. Acute Physiology and Chronic Health Evaluation (APACHE) II score determined at the time of positive blood culture was superior to other investigated models, correctly predicting survival status in 83% of the study cohort. In multivariate analysis accounting for APACHE II, receipt of inadequate empirical therapy was associated with nearly a twofold higher rate of death (adjusted hazard ratio 1.9, 95% confidence interval 1.1–3.4; p = 0.02). Multidrug-resistant K. pneumoniae accounted for two-thirds of all K. pneumoniae BSIs, high rates of inappropriate empirical therapy, and twofold higher rates of patient death irrespective of underlying illness.

Therapeutic Options for Resistant Gram Positives

Vancomycin remains the current gold standard for treatment of serious MRSA (methicillin resistant Staphylococcus aureus) infections despite uncertainties about rates of toxicity and the optimal dosing strategy. The only alternative for bloodstream infections (BSI) based on prospective randomised controlled trial data is daptomycin. However, higher doses should be implemented to prevent resistance emerging. Although linezolid and ceftaroline have been shown to be effective BSI treatment in retrospective cohort studies, there is no prospective randomised comparative data with vancomycin. These agents should thus be considered as salvage therapy options. In the treatment of MRSA cSSSIs (complicated skin and skin structure infections), daptomycin, linezolid, ceftaroline and telavancin have all been shown to be equally effective to vancomycin and thus the choice of agent is dependent on the side effect profile and patient setting. In the treatment of nosocomial MRSA pneumonia, both linezolid and telavancin have been shown to be non-inferior to vancomycin. Linezolid was shown to have improved microbiological and clinical cure rates compared with vancomycin, but with no mortality benefit in a randomised controlled trial by Wunderink et al., [1, 2]. Debate still exists, however, as to whether these studies, in the absence of a mortality benefit, provide sufficient evidence to recommend linezolid or telavancin above vancomycin in the treatment of MRSA pneumonia. For the treatment of VRE (Vancomycin Resistant Enterococci) BSI, prospective data is lacking and recommendations are based upon in vitro activity and cohort studies. Quinupristin-dalfopristin is limited by its side effect profile and the need for a central line. As such the first line agents include daptomycin and linezolid. Although two recent meta-analyses suggest improved outcomes with linezolid over daptomycin, this may reflect suboptimal daptomycin dosing rather than linezolid superiority. Tigecycline, although active against VRE, has been shown to be inferior in eradication rates compared with linezolid [3]. Combination therapy for MRSA or VRE infections cannot currently be endorsed and thus should be limited to settings where no other alternative is available.

Bacterial and antimicrobial resistance profile of bloodstream infections: A hospital-based study

Background: Bloodstream infections (BSIs) are one of the serious infections causing significant morbidity and mortality among hospitalized patients. Large numbers of cases of treatment failure are being reported due to emergence of drug resistance. Early microbiological diagnosis and determination of antimicrobial susceptibility pattern have been shown to improve treatment outcome. The present study was aimed to determine the bacterial and antimicrobial resistance profile of BSIs in a major tertiary care hospital. Materials and Methods: Blood samples in brain heart infusion (BHI) broth submitted to the microbiology laboratory for culture and sensitivity during a period of 1 year were included in the study. Samples were processed as per standard protocol of laboratory for isolation and identification. The antimicrobial susceptibility profile of bacterial isolates was determined by the disc diffusion method as per Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: Out of 4862 blood samples, 494 (10.16%) isolates were obtained. Of these isolates, 256 (51.82%) were Gram-negative and 230 (46.56%) were Gram-positive bacteria. The most commonly identified organism was coagulase-negative Staphylococcus (CoNS) (25.91%) followed by Acinetobacter spp. (20.24%) and Escherichia coli (14.98%). Gram-negative bacteria showed a higher rate of resistance as compared with Gram-positive bacteria. Conclusion: High prevalence of antimicrobial resistance was noted in this study, especially in Gram-negative bacteria. Hence, appropriate treatment of BSIs should be based on the current knowledge of bacterial resistance profile as provided by microbiology laboratory. It would be advisable for the clinicians to mandate antimicrobial sensitivity testing for suspected cases of BSIs.

Bloodstream infection caused by Campylobacter lari

We describe a case of bloodstream infection (BSI) caused by Campylobacter lari in a 58-year-old man diagnosed with lumbar pyogenic spondylitis. Anaerobic blood cultures, taken on the day of admission and on hospital day 4, were positive after 30h of incubation, although no bacteria were detected by Gram staining. After subculture on 5% sheep blood agar for 2days at 35°C in a 5% CO2 environment, capnophilic, curved, gram-negative bacteria were recovered. The bacteria were identified as C. lari using a combination of phenotypic identification methods and partial 16S rRNA gene sequencing. The BSI was eradicated following combination therapy with intravenous tazobactam/piperacillin, oral erythromycin, and sulfamethoxazole/trimethoprim. These results suggest that accurate identification, to the species level, is important to determine effective treatment of BSI caused by Campylobacter spp. and can help us to understand the epidemiology.

Molecular analysis and risk factors for Escherichia coli producing extended-spectrum β-lactamase bloodstream infection in hematological malignancies.

IntroductionPatients with hematologic malignancies have greater risk-factors for primary bloodstream infections (BSI).MethodsFrom 2004–2009, we analyzed bacteremia caused by extended-spectrum beta-lactamase Escherichia coli (ESBL-EC) (n = 100) and we compared with bacteremia caused by cephalosporin-susceptible E. coli (n = 100) in patients with hematologic malignancies.ObjectiveTo assess the clinical features, risk factors, and outcome of ESBL-EC BSI in patients with hematologic malignancies, and to study the molecular epidemiology of ESBL-EC isolates.ResultsThe main diagnosis was acute leukemia in 115 patients (57.5%). Death-related E. coli infection was significantly increased with ESBL-EC (34% vs. control group, 19%; p = 0.03). Treatment for BSI was considered appropriate in 64 patients with ESBL-EC (mean survival, 245±345 days), and in 45 control patients this was 443±613 (p = 0.03). In patients not receiving appropriate antimicrobial treatment, survival was significantly decreased in cases compared with controls (26±122 vs. 276±442; p = 0.001). Fifty six of the ESBL-EC isolates were characterized by molecular analysis: 47 (84%) expressed CTX-M-15, two (3.6%) SHV, and seven (12.5%) did not correspond to either of these two ESBL enzymes. No TLA-1 enzyme was detected.ConclusionsPatients who had been previously hospitalized and who received cephalosporins during the previous month, have an increased risk of ESBL-EC bacteremia. Mortality was significantly increased in patients with ESBL-EC BSI. A polyclonal trend was detected, which reflects non-cross transmission of multiresistant E.coli isolates.

Current management of bloodstream infections

Bloodstream infection (BSI) is a frequent complication of invasive infections. The presence of bacteremia has therapeutic and prognostic implications. Here we review recent changes in the epidemiology, diagnosis and treatment of BSI (excluding candidemia). The evidence of the impact of healthcare-association in many community-onset episodes and the increase in drug-resistant pathogens causing BSI in the community and hospitals is reviewed. The emergence of molecular methods as an alternative tool for the diagnosis of BSI and novel aspects of clinical management, particularly of some multidrug-resistant organisms. Several quality indicators related to the diagnosis and management of bacteremia in hospitals are proposed.

Bloodstream infections: the problem and the challenge

Bloodstream infections (BSI) are an indisputable cause of morbidity and mortality. These infections may originate in the community setting among healthy individuals or among patients actively receiving healthcare as on dialysis, chemotherapy, etc. The largest numbers of BSI, however, are nosocomial. Rates of nosocomial BSI are highest in ICU's but the greatest numbers of cases occur in non-ICU settings. Many are catheter related. Application of simple principles of intravenous catheter placement and maintenance can markedly reduce nosocomial BSI. Although treatment of BSI can be difficult, the greatest challenge is preventing these infections.

Daily cost of antimicrobial therapy in patients with Intensive Care Unit-acquired, laboratory-confirmed bloodstream infection

This study analysed daily antimicrobial costs of Intensive Care Unit (ICU)-acquired, laboratory-confirmed bloodstream infection (BSI) per patient admitted to the ICU of a university hospital, based on prospectively collected data over a 4-year period (2003–2006). Costs were calculated based on the price of the agent(s) initiated on the first day of appropriate treatment and according to: (i) focus of infection; (ii) pathogen; and (iii) antimicrobial agent. The study included 310 adult patients who developed 446 BSI episodes. Mean overall daily antimicrobial cost was €114.25. Daily antimicrobial cost was most expensive for BSIs with unknown focus (€137.70), followed by catheter-related (€122.73), pulmonary (€112.80), abdominal (€98.00), wound (€89.21), urinary (€87.85) and other inciting focuses (€81.59). Coagulase-negative staphylococci were the most prevalent pathogens isolated. Treatment of BSIs caused by Candida spp. was the most costly. The daily antimicrobial costs per infected patient with multidrug-resistant BSI was ca. 50% higher compared with those without (€165.09 vs. €82.67; P < 0.001). Among the total of 852 prescriptions, β-lactam antibiotics accounted for approximately one-third of the overall daily cost of antimicrobial agents. The antibiotic cost associated with ICU-acquired, laboratory-confirmed BSI is significant and should be reduced by implementing infection control measures and preventive strategies.

High antimicrobial resistance among bacterial isolates of blood stream infections (BSI) in a Nigerian University Teaching Hospital

The antimicrobial resistance profile of 220 bacteria isolated from 1,006 episodes of blood stream infections (BSI) between January 2004 and December 2005 in a University Teaching Hospital, Southwestern Nigeria, were analyzed. Gram positive bacteria constituted 47.3% while Gram negative constituted 52.7%. The most common organisms were Staphylococcus aureus (37.3%), Klebsiella (30%), Pseudomonas (8.2%), Proteus (6.4%), Escherichia coli (5.5%) and coagulase negative staphylococci (4.6%). The cumulative resistance of all the bacteria isolates to ampicillin was 79%, gentamicin 51%, ceftazidime 11% and ciprofloxacin 6%. About 85% of the Gram positive bacteria were resistant to penicillinG, 79% to methicillin and 37% to erythromycin while 74% of the Gram negative bacteria were resistant to cotrimoxazole, 69% to tetracycline and 38% to chloramphenicol. Among the 7 antibiotics tested for each group, 7 patterns of antibiotic resistance were observed for each; 6 were multi-drug pattern with number of antibiotics ranging from 2 to 7. This study demonstrates high antimicrobial resistance among clinical bacterial isolates of BSI to commonly prescribed antibiotics most especially penicillinG, ampicillin, methicillin, cotrimoxazole, tetracycline and gentamicin. Based on the result of this study, it is suggested that the combination of ampicillin and gentamicin normally employed for empirical treatment of BSI in our hospital should be stopped.

Blood culture Gram stain and clinical categorization based empirical antimicrobial therapy of bloodstream infection

Early antimicrobial treatment has a great influence on the outcome of patients with blood stream infections (BSI). The study was designed to see if the simple practice of patient categorization (community acquired, nosocomial or infection in haematological unit) combined with Gram stain data could be used to guide empirical treatment of BSI in 1901 consecutive positive blood culture findings. There were considerable differences in the occurrence of common pathogens and their antimicrobial susceptibilities between patient categories especially for Gram-positive cocci. For example, second generation cephalosporins covered more than 70% cocci in clusters and over 80% of cocci in chains in community acquired infections whereas in hospital acquired infections the corresponding figures were only 47 and 44%. We conclude that Gram stain results of positive blood cultures along with the knowledge of where the infection was acquired, would allow early accurate targeting of antimicrobial therapy for BSI.