Prevalence, Etiology, and Outcome of Sepsis among Critically Ill Patients in Malawi.

There are scarce data describing the etiology and clinical sequelae of sepsis in low- and middle-income countries (LMICs). This study describes the prevalence and etiology of sepsis among critically ill patients at a referral hospital in Malawi. We conducted an observational prospective cohort study of adults admitted to the intensive care unit or high-dependency unit (HDU) from January 29, 2018 to March 15, 2018. We stratified the cohort based on the prevalence of sepsis as defined in the following three ways: quick sequential organ failure assessment (qSOFA) score ≥ 2, clinical suspicion of systemic infection, and qSOFA score ≥ 2 plus suspected systemic infection. We measured clinical characteristics and blood and urine cultures for all patients; antimicrobial sensitivities were assessed for positive cultures. During the study period, 103 patients were admitted and 76 patients were analyzed. The cohort comprised 39% male, and the median age was 30 (interquartile range: 23-40) years. Eighteen (24%), 50 (66%), and 12 patients (16%) had sepsis based on the three definitions, respectively. Four blood cultures (5%) were positive, two from patients with sepsis by all three definitions and two from patients with clinically suspected infection only. All blood bacterial isolates were multidrug resistant. Of five patients with urinary tract infection, three had sepsis secondary to multidrug-resistant bacteria. Hospital mortality for patients with sepsis based on the three definitions ranged from 42% to 75% versus 12% to 26% for non-septic patients. In summary, mortality associated with sepsis at this Malawi hospital is high. Bacteremia was infrequently detected, but isolated pathogens were multidrug resistant.

Propensity-matched analysis of the impact of extended-spectrum ß-lactamase production on adults with community-onset Escherichia coli, Klebsiella species, and Proteus mirabilis bacteremia.

BACKGROUND: The presence of extended-spectrum ß-lactamase (ESBL) in Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP) is of great microbiological and clinical importance. The study dealing with the direct impact of ESBL producers on the outcome of patients with community-onset bacteremia is lacking. METHODS: Adults with community-onset EKP bacteremia were recruited retrospectively during a 6-year period. ESBL producers were determined according to ESBL phenotype. ESBL patients were compared on a 1:2 basis with non-ESBL patients by using propensity-score matching (PSM) calculated based on independent predictors of 28-day mortality. RESULTS: Of the 1141 eligible adult patients, 65 (5.7%) caused by ESBL producers. Significant differences between the two groups were discovered in the proportions of patients with critical illness (a Pitt bacteremia score ≥ 4) at bacteremia onset, inappropriate empirical antibiotic therapy, bacteremia because of urosepsis and pneumonia, and several comorbidities. In a PSM analysis after controlling for six independent predictors-critical illness at bacteremia onset, underlying fatal comorbidities (McCabe classification), inappropriate empirical antibiotic therapy, comorbidities with liver cirrhosis, bacteremia because of urosepsis and pneumonia-a appropriate matching between two groups (ESBL group, 60 patients; non-ESBL group, 120) were observed in age, causative microorganism, bacteremia severity, major comorbidities, comorbidity severity, and major bacteremia source. Consequently, a strong relationship between ESBL producers and poor prognosis was highlighted. CONCLUSIONS: The adverse influence of ESBL producers on clinical outcomes was presented with respect to adults with community-onset EKP bacteremia. Establishing a predictive scoring algorithm for identifying patients at risk of ESBL-producer infections is crucial.

The impact of production of extended-spectrum ß-lactamases on the 28-day mortality rate of patients with Proteus mirabilis bacteremia in Korea.

BACKGROUND: The incidence of Proteus mirabilis antimicrobial resistance, especially that mediated by extended-spectrum ß-lactamases (ESBLs), has increased. We investigated the impact of ESBL production on the mortality of patients with P. mirabilis bacteremia in Korea. METHODS: Patients diagnosed with P. mirabilis bacteremia between November 2005 and December 2013 at a 2000-bed tertiary care center in South Korea were included in this study. Phenotypic and molecular analyses were performed to assess ESBL expression. Characteristics and treatment outcomes were investigated among ESBL-producing and non-ESBL-producing P. mirabilis bacteremia groups. A multivariate analysis of 28-day mortality rates was performed to evaluate the independent impact of ESBLs. RESULTS: Among 62 P. mirabilis isolates from 62 patients, 14 expressed ESBLs (CTX-M, 2; TEM, 5; both, 6; other, 1), and the 28-day mortality rate of the 62 patients was 17.74%. No clinical factor was significantly associated with ESBL production. The 28-day mortality rate in the ESBL-producing group was significantly higher than that in the non-ESBL-producing group (50% vs. 8.3%, p = 0.001). A multivariate analysis showed that ESBL production (odds ratio [OR], 11.53, 95% confidence interval [CI], 2.11-63.05, p = 0.005) was independently associated with the 28-day mortality rate in patients with P. mirabilis bacteremia. CONCLUSIONS: ESBL production is significantly associated with mortality in patients with bacteremia caused by P. mirabilis. Rapid detection of ESBL expression and prompt appropriate antimicrobial therapy are required to reduce mortality caused by P. mirabilis bacteremia.

Propensity score-matched analysis comparing the therapeutic efficacies of cefazolin and extended-spectrum cephalosporins as appropriate empirical therapy in adults with community-onset Escherichia coli, Klebsiella spp. and Proteus mirabilis bacteraemia.

In this study, the therapeutic efficacy of cefazolin was compared with that of extended-spectrum cephalosporins (ESCs) (cefotaxime, ceftriaxone and ceftazidime) as appropriate empirical therapy in adults with community-onset monomicrobial bacteraemia caused by Escherichia coli, Klebsiella spp. or Proteus mirabilis (EKP). Compared with cefazolin-treated patients (n = 135), significantly higher proportions of patients in the ESC treatment group (n = 456) had critical illness at bacteraemia onset (Pitt bacteraemia score ≥4) and fatal co-morbidities (McCabe classification). Of the 591 patients, 121 from each group were matched using propensity score matching (PSM) based on the following independent predictors of 28-day mortality: fatal co-morbidities (McCabe classification); Pitt bacteraemia score ≥4 at bacteraemia onset; initial syndrome of septic shock; and bacteraemia due to pneumonia. After appropriate PSM, no significant differences were observed in the early clinical failure rate (10.7% vs. 7.4%; P = 0.37), the proportion of critical illness (Pitt bacteraemia score ≥4) (0% vs. 0%; P = 1.00) and defervescence (52.6% vs. 42.6%; P = 0.13) on Day 3 between the cefazolin and ESC treatment groups. Similarly, no significant differences were observed in the mean of time to defervescence (4.1 days vs. 4.9 days; P = 0.15), late clinical failure rate (18.2% vs. 10.7%; P = 0.10) and 28-day crude mortality rate (0.8% vs. 3.3%; P = 0.37) between the two groups. These data suggest that the efficacy of cefazolin is similar to that of ESCs when used as appropriate empirical antimicrobial treatment for community-onset EKP bacteraemia.

Cefepime shows good efficacy and no antibiotic resistance in pneumonia caused by Serratia marcescens and Proteus mirabilis - an observational study.

BACKGROUND: Many antibiotics have no effect on Gram-positive and Gram-negative microbes, which necessitates the prescription of broad-spectrum antimicrobial agents that can lead to increased risk of antibiotic resistance. These pathogens constitute a further threat because they are also resistant to numerous beta-lactam antibiotics, as well as other antibiotic groups. This study retrospectively investigates antimicrobial resistance in hospitalized patients suffering from pneumonia triggered by Gram-negative Serratia marcescens or Proteus mirabilis. METHODS: The demographic and clinical data analyzed in this study were obtained from the clinical databank of the HELIOS Clinic, Witten/Herdecke University, Wuppertal, Germany, for inpatients presenting with pneumonia triggered by S. marcescens or P. mirabilis from 2004 to 2014. An antibiogram was conducted for the antibiotics utilized as part of the management of patients with pneumonia triggered by these two pathogens. RESULTS: Pneumonia was caused by Gram-negative bacteria in 115 patients during the study period from January 1, 2004, to August 12, 2014. Of these, 43 (37.4 %) hospitalized patients [26 males (60.5 %, 95 % CI 45.9 %-75.1 %) and 17 females (39.5 %, 95 % CI 24.9 %-54.1 %)] with mean age of 66.2 ± 13.4 years had pneumonia triggered by S. marcescens, while 20 (17.4 %) patients [14 males (70 %, 95 % CI 49.9 %-90.1 %) and 6 females (30 %, 95 % CI 9.9 %-50.1 %)] with a mean age of 64.6 ± 12.8 years had pneumonia caused by P. mirabilis. S. marcescens showed an increased antibiotic resistance to ampicillin (100 %), ampicillin-sulbactam (100 %), and cefuroxime (100 %). P. mirabilis had a high resistance to tetracycline (100 %) and ampicillin (55 %). S. marcescens (P < 0.0001) and P. mirabilis (P = 0.0003) demonstrated no resistance to cefepime in these patients with pneumonia. CONCLUSIONS: S. marcescens and P. mirabilis were resistant to several commonly used antimicrobial agents, but showed no resistance to cefepime.

Effects of astaxanthin and emodin on the growth, stress resistance and disease resistance of yellow catfish (Pelteobagrus fulvidraco).

Yellow catfish (Pelteobagrus fulvidraco) has become a commercially important fish species in China and eastern Asia. High-density aquaculture has led to congestion and excessive stress and contributed to bacterial infection outbreaks that have caused high mortality. We investigated the effects of dietary supplementation with astaxanthin and emodin alone and in combination on the growth and stress resistance of yellow catfish. After 60 days of feeding, each group of fish (control, astaxanthin, emodin, and astaxanthin plus emodin (combination) groups) was exposed to acute crowding stress for 24 h, and a subsample of fish from the four groups was challenged with the bacterial septicemia pathogen Proteus mirabilis after the end of the crowding stress experiment. Compared with the control, the astaxanthin and emodin groups showed increases in serum total protein (TP), hepatic superoxide dismutase (SOD) activity and hepatic heat shock proteins 70 (HSP70) mRNA levels at 12 and 24 h after the initiation of crowding stress. The combination group exhibited increases in alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, serum TP, hepatic SOD activity and hepatic HSP70 mRNA levels within 24 h after the initiation of crowding stress. However, decreases relative to the control were observed in the serum cortisol and glucose contents in the three treatment groups at 12 and 24 h after the initiation of crowding stress, in ALT and AST activity in the astaxanthin and emodin group at 24 h after the initiation of crowding stress, and in the serum lysozyme activity, serum alkaline phosphatase (ALP) activity, and hepatic catalase (CAT) and malondialdehyde (MDA) activity in the combination group at 24 h after the initiation of crowding stress. Additionally, the cumulative mortality after P. mirabilis infection was lower in all three treatment groups (57.00%-70.33%) than in the control (77.67%). Dietary supplementation with astaxanthin and emodin decreased the specific growth rate (SGR) and weight gain (WG) of healthy yellow catfish, although significant differences in mortality were not observed. These results indicate that dietary supplementation with 80 mg/kg astaxanthin and 150 mg/kg emodin can improve the anti-oxidative capabilities, hepatic HSP70 levels, and resistance to acute crowding stress of yellow catfish. Finally, an appropriate strategy for enhance yellow catfish stress resistance and disease resistance is proposed.

Mass mortality in ornamental fish, Cyprinus carpio koi caused by a bacterial pathogen, Proteus hauseri.

Moribund koi carp, Cyprinus carpio koi, from a farm with 50% cumulative mortality were sampled with the aim of isolating and detecting the causative agent. Three bacterial species viz., Citrobacter freundii (NSCF-1), Klebsiella pneumoniae (NSKP-1) and Proteus hauseri [genomospecies 3 of Proteus vulgaris Bio group 3] (NSPH-1) were isolated, identified and characterized on the basis of biochemical tests and sequencing of the 16S rDNA gene using universal bacterial primers. Challenge experiments with these isolates using healthy koi carp showed that P. hauseri induced identical clinical and pathological states within 3 d of intramuscular injection. The results suggest P. hauseri (NSPH-1) was the causative agent. In phylogenetic analysis, strain NSPH-1 formed a distinct cluster with other P. hauseri reference strains with ≥99% sequence similarity. P. hauseri isolates were found sensitive to Ampicillin, Cefalexin, Ciprofloxacin and Cefixime and resistant to Gentamycin, Oxytetracycline, Chloramphenicol, and Kanamycin. The affected fish recovered from the infection after ciprofloxacin treatment.

Multidrug-resistant Proteus mirabilis bloodstream infections: risk factors and outcomes.

Our aims were to identify (i) risk factors associated with the acquisition of multidrug-resistant (MDR, to 3 or more classes of antimicrobials) Proteus mirabilis isolates responsible for bloodstream infections (BSIs) and (ii) the impact on mortality of such infections. Risk factors for acquiring MDR P. mirabilis BSIs were investigated in a case-case-control study; those associated with mortality were assessed by comparing survivors and nonsurvivors in a cohort study. The population consisted of 99 adult inpatients with P. mirabilis BSIs identified by our laboratory over an 11-year period (1999 to 2009), 36 (33.3%) of which were caused by MDR strains, and the overall 21-day mortality rate was 30.3%. Acquisition of an MDR strain was independently associated with admission from a long-term care facility (odds ratio [OR], 9.78; 95% confidence interval [CI], 1.94 to 49.16), previous therapy with fluoroquinolones (OR, 5.52; 95% CI, 1.30 to 23.43) or oxyimino-cephalosporins (OR, 4.72; 95% CI, 1.31 to 16.99), urinary catheterization (OR, 3.89; 95% CI, 1.50 to 10.09), and previous hospitalization (OR, 2.68; 95% CI, 10.4 to 6.89). Patients with MDR P. mirabilis BSIs received inadequate initial antimicrobial therapy (IIAT, i.e., treatment with drugs to which the isolate displayed in vitro resistance) more frequently than those with non-MDR infections; they also had increased mortality and (for survivors) longer post-BSI-onset hospital stays. In multivariate regression analysis, 21-day mortality was associated with septic shock at BSI onset (OR, 12.97; 95% CI, 32.2 to 52.23), P. mirabilis isolates that were MDR (OR, 6.62; 95% CI, 16.4 to 26.68), and IIAT (OR, 9.85; 95% CI, 26.7 to 36.25), the only modifiable risk factor of the 3. These findings can potentially improve clinicians' ability to identify P. mirabilis BSIs likely to be MDR, thereby reducing the risk of IIAT--a major risk factor for mortality in these cases--and facilitating the prompt implementation of appropriate infection control measures.

The new variant of Salmonella genomic island 1 (SGI1-V) from a Proteus mirabilis French clinical isolate harbours blaVEB-6 and qnrA1 in the multiple antibiotic resistance region.

OBJECTIVES: The clinical strain of Proteus mirabilis VB1248 isolated from a blood culture in August 2009 was multiresistant (i.e. resistant to ß-lactams, fluoroquinolones, aminoglycosides and sulphonamides). We searched for the presence of a Salmonella genomic island 1 (SGI1). METHODS: The whole genetic structure surrounding the genes involved in antibiotic resistance was characterized by PCR or gene walking followed by DNA sequencing. RESULTS: The new variant SGI1-V (42.9 kb) was located downstream of the thdF chromosomal gene. Genes sharing homology with phage-related genes were detected on a structure of 8.3 kb located between the right junction of the SGI1-V and the hipB/hipA genes. Some genetic rearrangements occurred in the SGI1-V backbone: an insertion of 2349 bp within the open reading frame (ORF) S014, and a deletion of 3766 bp in the region spanning from ORFs S021 to S025 leading to the lack of ORFs S023 and S024. The multidrug resistance (MDR) region of 17.1 kb was located on a complex class 1 integron extremely different from those described so far. The cassette array included aacA4, aadB and dhfrA1. Adjacent to this classical structure, bla(VEB-6) was found flanked by 135 bp elements and bracketed by two 3'-conserved segments (3'-CS). Downstream of the second copy of 3'-CS, the qnrA1 gene was associated with common region 1. CONCLUSIONS: We have identified in P. mirabilis the new variant SGI1-V containing the bla(VEB-6) and qnrA1 genes in the MDR region. This is the first report of an extended-spectrum ß-lactamase-encoding gene and a qnr determinant conferring resistance to quinolones on an SGI1-like structure. It might constitute a source of spread of resistance to other bacterial species.

Clinical and economic impact of bacteremia with extended- spectrum-beta-lactamase-producing Enterobacteriaceae.

We studied outcomes of extended-spectrum beta-lactamase (ESBL) production in Enterobacteriaceae bacteremia. Inpatients with bacteremia caused by ESBL-producing Escherichia coli, Klebsiella spp., or Proteus spp. (cases) were compared with patients with bacteremia caused by non-ESBL producers (controls). Outcomes included mortality, mortality due to infection, length of stay (LOS), delay in appropriate therapy (DAT), discharge to a chronic care facility, and hospital cost. Ninety-nine cases and 99 controls were enrolled. Thirty-five percent of cases died, versus 18% of controls (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.3 to 4.7; P=0.01). Thirty percent of cases died due to infection, versus 16% of controls (OR, 2.3; 95% CI, 1.1 to 4.5; P=0.03). The median LOS after bacteremia for cases was 11 days (interquartile range, 5 to 21), versus 5 days for controls (interquartile range, 3 to 9) (P<0.001). DAT occurred in 66% of cases, versus 7% of controls (OR, 25.1; 95% CI, 10.5 to 60.2; P<0.001). Cases were more likely than controls to be discharged to chronic care (52% versus 21%; OR, 4.0; 95% CI, 1.9 to 8.3; P<0.001). The average hospital cost for cases was 65,509 Israeli shekels, versus 23,538 shekels for controls (P<0.001). After adjusting for differences between groups by using multivariable analysis, ESBL production remained a significant predictor of mortality (OR, 3.6; 95% CI, 1.4 to 9.5; P=0.008), increased LOS (1.56-fold; P=0.001), DAT (OR, 25.1; 95% CI, 10.5 to 60.2; P<0.001), and increased cost (1.57-fold; P=0.003). The mean increase in equivalent cost attributable to ESBL production was $9,620. ESBL production was associated with severe adverse outcomes, including higher overall and infection-related mortality, increased LOS, DAT, discharge to chronic care, and higher costs.

Proteus mirabilis bloodstream infections: risk factors and treatment outcome related to the expression of extended-spectrum beta-lactamases.

Bloodstream infection (BSI) due to Proteus mirabilis strains is a relatively uncommon clinical entity, and its significance has received little attention. This study was initiated to evaluate risk factors and treatment outcome of BSI episodes due to P. mirabilis producing extended-spectrum beta-lactamases (ESBLs). Twenty-five BSI episodes caused by P. mirabilis occurred at our hospital (Ospedale di Circolo e Fondazione Macchi, Varese, Italy) over a 7.5-year period. Phenotypic and molecular methods were used to assess ESBL production. Clinical records of BSI patients were examined retrospectively. Demographic data, underlying diseases (according to McCabe and Jackson classification and Charlson weighted index), risk factors, and treatment outcome were investigated by comparing cases due to ESBL-positive strains to cases due to ESBL-negative strains. Eleven isolates were found to express ESBLs (TEM-52 or TEM-92). The remaining 14 isolates were ESBL negative and were uniformly susceptible to extended-spectrum cephalosporins and monobactams. Comparison of the two groups showed that previous hospitalization in a nursing home (P = 0.04) and use of bladder catheter (P = 0.01) were significant risk factors for infections due to ESBL-positive strains. In addition, cases due to ESBL-positive strains showed a significantly higher mortality attributable to BSI (P = 0.04). BSI cases due to ESBL-negative isolates uniformly responded to therapy, whereas 5/11 cases due to ESBL-positive isolates failed to respond (P < 0.01). Use of carbapenems was associated with complete response independently of ESBL production. Therapeutic failure and mortality may occur in BSI episodes caused by ESBL-positive P. mirabilis isolates. Thus, recognition of ESBL-positive strains appears to be critical for the clinical management of patients with systemic P. mirabilis infections.

Protean infectious types and frequent association with neurosurgical procedures in adult Serratia marcescens CNS infections: report of two cases and review of the literature.

Serratia marcescens is a rare pathogen of adult central nervous system (CNS) infection. We report on the clinical features and therapeutic outcomes of two adult patients with such infections. The clinical characteristics of 13 other reported adult cases are also included for analysis. The 15 cases were nine males and six females, aged 19-83 years, in whom, underlying post-neurosurgical states and ear operation were noted in 93% (14/15). Fever and conscious disturbance were the most common clinical manifestations of these 15 cases, followed by hydrocephalus, seizures, and wound infections. The manifestation types were protean, including meningitis and focal suppurations such as brain abscess, cranial and spinal epidural abscess, cranial subdural abscess, and infected lumbar pseudomeningocele. One case of S. marcescens CNS infection was diagnosed postmortem; the other 14 were diagnosed by the positive culture from CSF or pus. Antibiotic therapy with or without neurosurgical intervention was the management strategy in 14/15 cases. The therapeutic results showed a high mortality rate.

Serum immunoglobulin response and protection from homologous challenge by Proteus mirabilis in a mouse model of ascending urinary tract infection.

We tested the hypothesis that experimental Proteus mirabilis urinary tract infection in mice would protect against homologous bladder rechallenge. Despite production of serum immunoglobulin G (IgG) and IgM (median titers of 1:320 and 1:80, respectively), vaccinated (infected and antibiotic-cured) mice did not show a decrease in mortality upon rechallenge; the survivors experienced only modest protection from infection (mean log(10) number of CFU of P. mirabilis Nal(r) HI4320 per milliliter or gram in vaccinated mice versus sham-vaccinated mice: urine, 100-fold less [3.5 versus 5.5; P = 0.13]; bladder, 100-fold less [3.1 versus 5.1; P = 0.066]; kidneys, 40-fold less [2.7 versus 4.3; P = 0.016]). Western blots using protein from the wild-type strain and isogenic mutants demonstrated antibody responses to MR/P and PMF fimbriae and flagella. There was no correlation between serum IgG or IgM levels and protection from mortality or infection. There was a trend toward elevated serum IgA titers and protection from subsequent challenge (P >/= 0.09), although only a few mice developed significant serum IgA levels. We conclude that prior infection with P. mirabilis does not protect significantly against homologous challenge.

[The effect of erythromycin on immunity in immunodeficiency]. / Vliianie éritromitsina na immunitet pri immunodefitsite.

The effect of 12.5 and 25 mg/kg doses of erythromycin on the immunity of intact mice and in cyclophosphan- and azathioprine-induced immunodeficiency was studied. Erythromycin has no effect on the number of antibody-forming cells in the spleen of intact and immunocompromised with cyclophosphan animals. It increases their number against the background of azathioprine. Immunosuppression may change the character of the effect of erythromycin on delayed hypersensitivity. Erythromycin stimulates phagocyte activity in intact animals and in immunosuppression.

[The immunotropic properties of rifampicin and their correction]. / Immunotropnye svoistva rifampitsina i ikh korrektsiia.

The effect of rifampicin on antibody genesis depends on the dose, duration, and time of its administration in relation to the antigen, as well as on the character of immunosuppression. The antibiotic has no effect on delayed hypersensitivity and stimulates the activity of phagocytes, predominantly that of neutrophils. The effectiveness of rifampicin in experimental infection is maintained in treatment with cyclophosphane and azathioprine. When administered in combination with rifampicin and cytostatics methyluracil possesses a broader spectrum of immunostimulating activity than that of prodigiosin and levamisole.

[Antibacterial chemotherapy of "septic kidney"]. / Antibakterielle Chemotherapie der "Septischen Niere".

In the present retrospective study we report on antibacterial chemotherapy in patients suffering from a septic kidney. The results were documented in a course table, in which the septic parameters were divided into scores from 0 to 4 allowing to follow each patient's course with respect to the indicated scores. Two antibacterial substances were applied as short infusions with intervals of 4-6 hours between the administration of the different substances (Innsbruck scheme of chemotherapy). In all cases within 6 days from the onset of this therapy the septic parameters turned to normal values. None of the 24 patients suffering from a severe course of urosepsis, all treated at the University Hospital of Urology in Innsbruck between 1980 and 1990, died.

[The effect of catecholaminergic agents on the efficacy of immunostimulants]. / Vliianie katekholaminergicheskikh sredstv na éffektivnost' immunostimuliatorov.

The influence of combinations of immunostimulants (prodigiosin, methyluracil, levamisole) and catecholaminergic agents (dopamine, haloperidol, noradrenaline, phentolamine, isoproterenol, propranolol) on the results of antibiotic therapy of acute generalized Proteus infection and primary immune response to ram erythrocytes was studied on outbred albino mice. It was established that the agents influencing dopaminergic, alpha- and beta-adrenergic receptors can in some cases change the efficiency of the studied immunostimulants. The direction and degree of their action depend on the administration schedule.

Bacteremia in a long-term care facility. Spectrum and mortality.

One hundred episodes of bacteremia were studied in a primarily geriatric population. Gram-positive bacteremia accounted for 24% of all bacteremia (50% mortality rate), while gram-negative bacteremia accounted for 67% of bacteremia (25% mortality); 9% of all bacteremias were polymicrobial in nature (67% mortality). Overall mortality was 35%. The urinary tract was the most frequently identified tissue source (56%) followed by skin and subcutaneous tissue (14%) and respiratory tract (10%). Escherichia coli, Proteus species, and Klebsiella enterobacter group were the most common gram-negative organisms, Staphylococcus aureus was the most common gram-positive organism and together they accounted for approximately 75% of all bacteremia. Fifty percent of deaths occurred within 24 hours of diagnosis of bacteremia, despite appropriate antibiotic therapy. This study may help to identify risk factors for bacteremia in elderly patients.

The association of aminoglycoside plasma levels with mortality in patients with gram-negative bacteremia.

To determine the association of aminoglycoside levels with mortality from gram-negative bacteremia, we analyzed the case reports of patients from four prospective, randomized, and controlled clinical trials of gentamicin, tobramycin, and amikacin. Twelve (13.5%) of 89 patients died. One (2.4%) death occurred in 41 patients with early (1-hr postinfusion) peak concentrations of greater than 5 micrograms/ml of gentamicin and tobramycin and of greater than 20 micrograms of amikacin/ml; nine deaths (20.9%) occurred in 43 patients with lower concentrations. Five (8.3%) deaths occurred in 60 patients with mean peak concentrations for the entire course of therapy of greater than 5 micrograms/ml of gentamicin and tobramycin and of greater than 20 micrograms of amikacin/ml; five (20.8%) deaths occurred in 24 patients with lower concentrations. Stepwise discriminant analysis showed that therapeutic early peak concentration was a significant factor in the presence of three other factors: severity of underlying illness, peak temperature, and initial leukocyte count. The results suggest the importance of achieving adequate early aminoglycoside levels in patients with gram-negative bacteremia.

[Mortality of rare purulent meningitis, (Staphylococcus, Listeria Pseudomonas, Proteus, Klebsiella, E. coli, Salmonella). An epidemiologic study using the literature from the last 30 years]. / Die Letalitäten der seltenen eitrigen Meningitiden (Staphylokokken, Listerien, Pseudomonas, Proteus, Klebsiellen, E. coli, Salmonellen). Eine epidemiologische Studie anhand der Literatur der letzten 30 Jahre.

3056 cases of purulent meningitis caused by seven rare microorganisms (Staphylococci, Listeria, Pseudomonas, Proteus, Klebsiella, E. coli, Salmonella) were collected from the West European and North American literature of the last 30 years. The average lethality has been calculated for the periods ranging from 1948 to 1962 and from 1963 to 1979 in order to compare the results due to the use of penicillin and older antibiotics with those accomplished with ampicillin and the aminoglycosides. After 1963 the death-rate of each type of meningitis decreased considerably (except for Salmonella meningitis): the lethality of the whole group fell from 48% to 33%, in the subgroup of gram-negative meningitis from 55% to 38%, and in the group of neonatal gram-negative meningitis from 67% to 52%. The best results were seen in Proteus meningitis where lethality decreased from 55% to 15%. In E. coli meningitis there was a reduction from 60% to 43% only. Using the chi-square test all these differences were highly significant (p less than 0.001).