Hilmar Wisplinghoff

Nosocomial Bloodstream Infections in US Hospitals: Analysis of 24,179 Cases from a Prospective Nationwide Surveillance Study

BACKGROUND Nosocomial bloodstream infections (BSIs) are important causes of morbidity and mortality in the United States. METHODS Data from a nationwide, concurrent surveillance study (Surveillance and Control of Pathogens of Epidemiological Importance [SCOPE]) were used to examine the secular trends in the epidemiology and microbiology of nosocomial BSIs. RESULTS Our study detected 24,179 cases of nosocomial BSI in 49 US hospitals over a 7-year period from March 1995 through September 2002 (60 cases per 10,000 hospital admissions). Eighty-seven percent of BSIs were monomicrobial. Gram-positive organisms caused 65% of these BSIs, gram-negative organisms caused 25%, and fungi caused 9.5%. The crude mortality rate was 27%. The most-common organisms causing BSIs were coagulase-negative staphylococci (CoNS) (31% of isolates), Staphylococcus aureus (20%), enterococci (9%), and Candida species (9%). The mean interval between admission and infection was 13 days for infection with Escherichia coli, 16 days for S. aureus, 22 days for Candida species and Klebsiella species, 23 days for enterococci, and 26 days for Acinetobacter species. CoNS, Pseudomonas species, Enterobacter species, Serratia species, and Acinetobacter species were more likely to cause infections in patients in intensive care units (P<.001). In neutropenic patients, infections with Candida species, enterococci, and viridans group streptococci were significantly more common. The proportion of S. aureus isolates with methicillin resistance increased from 22% in 1995 to 57% in 2001 (P<.001, trend analysis). Vancomycin resistance was seen in 2% of Enterococcus faecalis isolates and in 60% of Enterococcus faecium isolates. CONCLUSION In this study, one of the largest multicenter studies performed to date, we found that the proportion of nosocomial BSIs due to antibiotic-resistant organisms is increasing in US hospitals.

Current Trends in the Epidemiology of Nosocomial Bloodstream Infections in Patients with Hematological Malignancies and Solid Neoplasms in Hospitals in the United States

A total of 2340 patients with underlying malignancy were identified among 22,631 episodes of nosocomial bloodstream infections (BSIs) in a prospectively collected database for 49 hospitals in the United States (Surveillance and Control of Pathogens of Epidemiologic Importance [SCOPE] Project). Data were obtained for the period of March 1995 through February 2001. Gram-positive organisms accounted for 62% of all BSIs in 1995 and for 76% in 2000 (P<.001), and gram-negative organisms accounted for 22% and 14% of all BSIs for these years, respectively. Neutropenia was observed in 30% of patients, so neutropenic and nonneutropenic patients were compared. In both, the predominant pathogens were coagulase-negative staphylococci (32% of isolates recovered from neutropenic patients and 30% of isolates recovered from nonneutropenic patients). The source of BSI was not determined for 57% of patients. The crude mortality rate was 36% for neutropenic patients and 31% for nonneutropenic patients.

Development of a Multilocus Sequence Typing Scheme for Characterization of Clinical Isolates of Acinetobacter baumannii

ABSTRACT In this study a multilocus sequence typing (MLST) scheme for Acinetobacter baumannii was developed and evaluated by using 40 clinical A. baumannii isolates recovered from outbreaks in Spanish and German hospitals during the years 1990 to 2001, as well as isolates from other European hospitals and two DSMZ reference strains of A. baumannii. For comparison, two isolates of Acinetobacter species 13 (sensu Tjernberg and Ursing), two clinical isolates, and three DSMZ strains of A. calcoaceticus (both belonging to the A. calcoaceticus-A. baumannii complex) were also investigated. Primers were designed for conserved regions of housekeeping genes, and 305- to 513-bp internal fragments of seven such genes—gltA, gyrB, gdhB, recA, cpn60, gpi, and rpoD—were sequenced for all strains. The number of alleles at individual loci ranged from 6 to 12, and a total of 20 allelic profiles or sequence types were distinguished among the investigated A. baumannii strains. The MLST data were in high concordance with the epidemiologic typing results generated by pulsed-field gel electrophoresis and amplified fragment length polymorphism fingerprinting. The MLST scheme provides a high level of resolution and an excellent tool for studying the population structure and long-term epidemiology of A. baumannii.

Nosocomial bloodstream infections in pediatric patients in United States hospitals: epidemiology, clinical features and susceptibilities.

Background. We identified the predominant pathogens and antimicrobial susceptibilities of nosocomial bloodstream isolates in pediatric patients in the US Prospective surveillance for nosocomial bloodstream infections at 49 hospitals during a 6-year period [Surveillance and Control of Pathogens of Epidemiologic Importance (SCOPE)] detected 22 609 bloodstream infections, of which 3432 occurred in patients ≤16 years of age. Results. Gram-positive organisms accounted for 65% of cases, Gram-negative organisms accounted for 24% of cases and 11% were caused by fungi. The overall crude mortality was 14% (475 of 3432) but notably higher for infections caused by Candida spp. and Pseudomonas aeruginosa, 20 and 29%, respectively. The most common organisms were coagulase-negative staphylococci (43%), enterococci, Staphylococcus aureus and Candida spp. (each, 9%). The mean interval between admission and infection averaged 21 days for coagulase-negative staphylococci, 25 days for S. aureus and Candida spp., 32 days for Klebsiella spp. and 34 days for Enterococcus spp. The proportion of methicillin-resistant S. aureus increased from 10% in 1995 to 29% in 2001. Vancomycin-resistance was seen in 1% of Enterococcus faecalis and in 11% of Enterococcus faecium isolates. Conclusion. Nosocomial BSI occurred predominantly in very young and/or critically ill children. Gram-positive pathogens predominated across all ages, and increasing antimicrobial resistance was observed in pediatric patients.

Nosocomial Bloodstream Infections Caused by Acinetobacter Species in United States Hospitals: Clinical Features, Molecular Epidemiology, and Antimicrobial Susceptibility

We examined the clinical and epidemiological features of nosocomial bloodstream infections (BSIs) caused by Acinetobacter species and observed from 1 March 1995 through 28 February 1998 at 49 United States hospitals (SCOPE National Surveillance Program). Acinetobacter species were found in 24 hospitals (49%) and accounted for 1.5% of all nosocomial BSIs reported. One hundred twenty-nine isolates were identified either as A. baumannii (n=111) or other Acinetobacter species (n=18). Patients with A. baumannii BSI, compared with patients with nosocomial BSI caused by other gram-negative pathogens, were more frequently observed in the intensive care unit (69% vs. 47%, respectively; P<.001; odds ratio [OR] 2.4; 95% confidence interval [CI] 1.6-3.7) and were more frequently receiving mechanical ventilation (58% vs. 30%, respectively; P<.001; OR 3.2; 95% CI 2.1-4.8). Crude mortality in patients with A. baumannii BSI was 32%. Molecular relatedness of strains was studied by use of polymerase chain reaction-based fingerprinting. Clonal spread of a single strain occurred in 5 hospitals. Interhospital spread of epidemic A. baumannii strains was not observed. The most active antimicrobial agents against A. baumannii (90% minimum inhibitory concentration values) were imipenem (1 mg/L; 100% of isolates susceptible), amikacin (8 mg/L; 96%), tobramycin (4 mg/L; 92%), and doxycycline (4 mg/L; 91%). Thirty percent of isolates were resistant to > or =4 classes of antimicrobials and were considered to be multidrug resistant.

Nosocomial bloodstream infections due to Candida spp. in the USA: species distribution, clinical features and antifungal susceptibilities

Candida spp. are among the most frequent nosocomial pathogens, contributing significantly to morbidity and mortality. Longitudinal data on the epidemiology of Candida bloodstream infections (BSIs) are still limited. Isolates and clinical data from 1218 episodes of Candida BSI were prospectively collected from patients in 52 hospitals in the USA between 1998 and 2006. Susceptibilities to amphotericin B, flucytosine, fluconazole, posaconazole, voriconazole, anidulafungin, caspofungin and micafungin were determined for 1077 Candida isolates by the CLSI reference broth microdilution method using the recently published species-specific clinical breakpoints. Candida albicans was the most prevalent species (50.7%), followed by Candida parapsilosis (17.4%), Candida glabrata (16.7%) and Candida tropicalis (10.2%). The prevalence of non-albicans Candida spp. increased over time. Patients had a mean age of 51 years and a mean length of hospital stay prior to BSI of 22 days. The main underlying conditions were gastrointestinal (20.1%) and pulmonary (13.0%) diseases. Intravenous catheters (19.1%) and the urinary tract (8.0%) were the most frequently determined likely sources, whilst in the majority of patients (61.1%) no source could be identified. Overall mortality was 38.1%. Of the isolates studied, 0.8% of C. albicans, 100.0% of C. glabrata, 2.9% of C. parapsilosis and 4.9% of C. tropicalis were non-susceptible to fluconazole, and 0.6% of C. albicans, 5.0% of Candida krusei, 7.6% of C. parapsilosis and 9.8% of C. tropicalis were non-susceptible to voriconazole. All echinocandins showed good activity against most Candida spp., including the majority of C. parapsilosis isolates, but only 38.1% of C. glabrata tested susceptible to caspofungin.

Risk Factors for Nosocomial Bloodstream Infections Due to Acinetobacter baumannii: A Case-Control Study of Adult Burn Patients

Risk factors for Acinetobacter baumannii bloodstream infection (BSI) were studied in patients with severe thermal injury in a burn intensive care unit where A. baumannii was endemic. Of 367 patients hospitalized for severe thermal injury during the study period, 29 patients with nosocomial A. baumannii BSI were identified (attack rate, 7.9%). Cases were compared with 58 matched controls without A. baumannii BSI. The overall mortality rate was 31% among cases and 14% among controls; only two deaths (7%) were considered directly related to A. baumannii BSI. Molecular typing of A. baumannii blood isolates by means of randomly amplified polymorphic DNA analysis and pulsed-field gel electrophoresis revealed the presence of three different strain types. Multivariate analysis showed that female gender (P = .027), total body surface area burn of > 50% (P = .016), prior nosocomial colonization with A. baumannii at a distant site (P = .0002), and use of hydrotherapy (P = .037) were independently associated with the acquisition of A. baumannii BSI in burn patients. These data underscore the need for effective infection control measures for this emerging nosocomial problem.

Clinical effectiveness of posaconazole prophylaxis in patients with acute myelogenous leukaemia (AML): a 6 year experience of the Cologne AML cohort

BACKGROUND Large randomized controlled trials have shown significant decreases in morbidity and mortality in leukaemia patients with posaconazole prophylaxis. However, the value of prophylaxis has been questioned in centres with a low incidence of invasive fungal diseases (IFDs) and pre-emptive treatment strategies. METHODS We prospectively evaluated the epidemiology of IFDs in acute myelogenous leukaemia (AML) patients undergoing first remission-induction chemotherapy before and after posaconazole prophylaxis had been introduced as a standard of care. Patients admitted from January 2003 to December 2005 received topical polyenes as antifungal prophylaxis (first group), while those admitted between January 2006 and December 2008 received 200 mg of oral posaconazole three times daily (second group). Other diagnostic and therapeutic standard operating procedures remained unchanged. RESULTS A total of 82 patients in the polyene prophylaxis group and 77 in the posaconazole prophylaxis group were included in the final analysis. Baseline characteristics were well matched between groups. Patients receiving topical polyene prophylaxis were more likely to experience breakthrough IFDs (19.5% and 3.9%; P = 0.003) or breakthrough aspergillosis (13.4% and 2.6%; P = 0.018) than patients receiving systemic posaconazole prophylaxis. They also had more febrile days (mean 10.7 +/- 9.66 and 7.3 +/- 5.73; P = 0.007), longer need for inpatient treatment (mean 53.0 +/- 24.16 and 46.0 +/- 14.39; P = 0.026) and a shorter fungal-free survival (78.7 and 90.4 days; P = 0.024). No significant differences were observed for persistent fever, pneumonia, lung infiltrates indicative of invasive pulmonary aspergillosis, or attributable and overall mortality. CONCLUSIONS After introduction of posaconazole prophylaxis for patients with AML, the number of febrile days, the incidence rate of IFDs and aspergillosis and the duration of hospitalization decreased significantly.

Bloodstream infection in neutropenic cancer patients related to short-term nontunnelled catheters determined by quantitative blood cultures, differential time to positivity, and molecular epidemiological typing with pulsed-field gel electrophoresis.

ABSTRACT To determine the rate of catheter-related bloodstream infection (CRBSI) among cases of primary bloodstream infection (BSI) in febrile neutropenic cancer patients with short-term nontunnelled catheters, quantitative paired blood cultures (Isolator) from the central venous catheter (CVC) and peripheral vein were obtained between November 1999 and January 2001. Bactec blood culture bottles were obtained to determine the differential time to positivity (DTP). CRBSI was defined as a quantitative blood culture ratio of >5:1 (CVC versus peripheral) with proven identity of isolates from positive peripheral and CVC blood cultures as confirmed by pulsed-field gel electrophoresis. Forty-nine episodes of primary BSI were detected among 235 cancer patients with febrile neutropenia. Of these, 18 episodes (37%) were CRBSI and 31 (63%) were BSI with an unknown portal of entry. Coagulase-negative staphylococci were present in nine cases of CRBSI (50%). The identity of isolates from peripheral and CVC blood cultures was confirmed in all cases. Earlier positivity (>2 h) of CVC-drawn versus peripheral blood cultures was observed in 18 of 22 CRBSI-associated blood cultures (sensitivity, 82%; specificity, 88%; positive predictive value, 75%; negative predictive value, 92%). In summary, CRBSI accounted for 37% of cases of primary BSI in this population of neutropenic cancer patients. DTP compares favourably with quantitative blood cultures for the diagnosis of CRBSI and may be particularly useful for patients in whom catheter salvage is highly desirable.

In Vitro Activities of the β-Lactamase Inhibitors Clavulanic Acid, Sulbactam, and Tazobactam Alone or in Combination with β-Lactams against Epidemiologically Characterized Multidrug-Resistant Acinetobacter baumannii Strains

ABSTRACT Acinetobacter baumannii is an important nosocomial pathogen usually in the context of serious underlying disease. Multidrug resistance in these organisms is frequent. The β-lactamase inhibitors clavulanic acid, sulbactam, and tazobactam have intrinsic activity against Acinetobacter strains. To evaluate their potential therapeutic usefulness, we determined the in vitro activity of ampicillin, sulbactam, ampicillin-sulbactam, cefoperazone, cefoperazone-sulbactam, piperacillin, piperacillin-sulbactam, tazobactam, piperacillin-tazobactam, amoxicillin, clavulanic acid, amoxicillin-clavulanic acid, ticarcillin, and ticarcillin-clavulanic acid against multidrug-resistant A. baumannii. All isolates were epidemiologically characterized by RAPD [random(ly) amplified polymorphic DNA] analysis and/or pulsed-field gel electrophoresis and represented different strain types, including sporadic strains, as well as outbreak-related strains. The MICs were determined by agar dilution on Mueller-Hinton agar (using fixed concentrations, as well as fixed ratios for β-lactamase inhibitors) and the E-test. The majority of E-test results were within two dilutions of those recorded by agar dilution, with the exception of piperacillin-tazobactam. Sulbactam was superior to clavulanic acid and tazobactam and may represent an alternative treatment option for infections due to multiresistant A. baumannii strains. β-Lactamase inhibitors have intrinsic activity but do not enhance activity of β-lactams against A. baumannii. Testing with the inhibitor added at a fixed concentration as recommended for piperacillin-tazobactam and ticarcillin-clavulanic acid by the National Committee for Clinical Laboratory Standards may falsely suggest high activity or gives uninterpretable results due to trailing. If combinations are used for testing, fixed ratios may give more useful results.