Allan L. Truant

Morphine Induces Sepsis in Mice

Gram-negative sepsis and subsequent endotoxic shock remain major health problems in the United States. The present study examined the role of morphine in inducing sepsis. Mice administered morphine by the subcutaneous implantation of a slow-release pellet developed colonization of the liver, spleen, and peritoneal cavity with gram-negative and other enteric bacteria. In addition, the mice became hypersusceptible to sublethal endotoxin challenge. The effects were blocked by the simultaneous implantation of a pellet containing the opioid antagonist naltrexone. These findings show that morphine pellet implantation in mice results in the escape of gram-negative organisms from the gastrointestinal tract, leading to the hypothesis that morphine used postoperatively or chronically for analgesia may serve as a cofactor in the precipitation of sepsis and shock. In addition, morphine-induced sepsis may provide a physiologically relevant model of gram-negative sepsis and endotoxic shock.

Potential Clindamycin Resistance in Clindamycin-Susceptible, Erythromycin-Resistant Staphylococcus aureus: Report of a Clinical Failure

ABSTRACT The erm gene product confers clindamycin resistance on Staphylococcus aureus. We report a clindamycin clinical failure where resistance developed on therapy in a D-test-positive strain. D tests of 91 clindamycin-susceptible, erythromycin-resistant S. aureus isolates showed that 68% of methicillin-susceptible and 12.3% of methicillin-resistant S. aureus strains were D-test positive.

Cladophialophora bantiana brain abscess in a solid-organ transplant recipient: case report and review of the literature.

ABSTRACT Cerebral phaeohyphomycosis caused by Cladophialophora bantiana is a rare disease. We describe a heart and bilateral lung transplant recipient who was unsuccessfully treated for a C. bantiana brain abscess. This report compares the present case to those of other solid-organ transplant recipients with the same infection and to those of patients who did not receive transplants.

Innate immune responses to systemic Acinetobacter baumannii infection in mice: neutrophils, but not interleukin-17, mediate host resistance.

ABSTRACT Acinetobacter baumannii is a nosocomial pathogen with a high prevalence of multiple-drug-resistant strains, causing pneumonia and sepsis. The current studies further develop a systemic mouse model of this infection and characterize selected innate immune responses to the organism. Five clinical isolates, with various degrees of antibiotic resistance, were assessed for virulence in two mouse strains, and between male and female mice, using intraperitoneal infection. A nearly 1,000-fold difference in virulence was found between bacterial strains, but no significant differences between sexes or mouse strains were observed. It was found that microbes disseminated rapidly from the peritoneal cavity to the lung and spleen, where they replicated. A persistent septic state was observed. The infection progressed rapidly, with mortality between 36 and 48 h. Depletion of neutrophils with antibody to Ly-6G decreased mean time to death and increased mortality. Interleukin-17 (IL-17) promotes the response of neutrophils by inducing production of the chemokine keratinocyte-derived chemoattractant (KC/CXCL1), the mouse homolog of human IL-8. Acinetobacter infection resulted in biphasic increases in both IL-17 and KC/CXCL1. Depletion of neither IL-17 nor KC/CXCL1, using specific antibodies, resulted in a difference in bacterial burdens in organs of infected mice at 10 h postinfection. Comparison of bacterial burdens between IL-17a −/− and wild-type mice confirmed that the absence of this cytokine did not sensitize mice to Acinetobacter infection. These studies definitely demonstrate the importance of neutrophils in resistance to systemic Acinetobacter infection. However, neither IL-17 nor KC/CXCL1 alone is required for effective host defense to systemic infection with this organism.

Morphine Withdrawal Lowers Host Defense to Enteric Bacteria: Spontaneous Sepsis and Increased Sensitivity to Oral Salmonella enterica Serovar Typhimurium Infection

ABSTRACT Understanding the consequences of drug withdrawal on immune function and host defense to infection is important. We, and others, previously demonstrated that morphine withdrawal results in immunosuppression and sensitizes to lipopolysaccharide-induced septic shock. In the present study, the effect of morphine withdrawal on spontaneous sepsis and on oral infection with Salmonella enterica serovar Typhimurium was examined. Mice were chronically exposed to morphine for 96 h by implantation of a slow-release morphine pellet. Abrupt withdrawal was induced by removal of the pellet. In the sepsis model, bacterial colonization was examined and bacterial species were identified by necropsy of various tissues. It was found that at 48 h postwithdrawal, morphine-treated mice had enteric bacteria that were detected in the Peyers patches (4/5), mesenteric lymph nodes (4/5), spleens (4/10), livers (6/10), and peritoneal cavities (8/10). In placebo pellet-withdrawn mice, only 2/40 cultures were positive. The most frequently detected organisms in tissues of morphine-withdrawn mice were Enterococcus faecium followed by Klebsiella pneumoniae. Both organisms are part of the normal gastrointestinal flora. In the infection model, mice were orally inoculated with S. enterica 24 h post-initiation of abrupt withdrawal from morphine. Withdrawal significantly decreased the mean survival time and significantly increased the Salmonella burden in various tissues of infected mice compared to placebo-withdrawn animals. Elevated levels of the proinflammatory cytokines were observed in spleens of morphine-withdrawn mice, compared to placebo-withdrawn mice. These findings demonstrate that morphine withdrawal sensitizes to oral infection with a bacterial pathogen and predisposes mice to bacterial sepsis.

Bacteria Adhere Less to Barbed Monofilament Than Braided Sutures in a Contaminated Wound Model

BackgroundPrevious studies have found fewer clinical infections in wounds closed with monofilament suture compared with braided suture. Recently, barbed monofilament sutures have shown improved strength and increased timesavings over interrupted braided sutures. However, the adherence of bacteria to barbed monofilament sutures and other commonly used suture materials is unclear.Questions/PurposesWe therefore determined: (1) the adherence of bacteria to five suture types including a barbed monofilament suture; (2) the ability to culture bacteria after gentle washing of each suture type; and (3) the pattern of bacterial adherence.MethodsWe created an experimental contaminated wound model using planktonic methicillin-resistant Staphylococcus aureus (MRSA). Five types of commonly used suture material were used: Vicryl™, Vicryl™ Plus, PDS™, PDS™ Plus, and Quill™. To determine adherence, we determined the number of bacteria removed from the suture by sequential washes. Sutures were plated to determine bacterial growth. Sutures were examined under confocal microscopy to determine adherence patterns.ResultsThe barbed monofilament suture showed the least bacterial adherence of any suture material tested. Inoculated monofilament and barbed monofilament sutures placed on agar plates had less bacterial growth than braided suture, whereas antibacterial monofilament and braided sutures showed no growth. Confocal microscopy showed more adherence to braided suture than to the barbed monofilament or monofilament sutures.ConclusionsBarbed monofilament suture showed similar bacterial adherence properties to standard monofilament suture.Clinical RelevanceOur findings suggest barbed monofilament suture can be substituted for monofilament suture, at the surgeon’s discretion, without fear of increased risk of infection.

The detection of positive blood cultures by the AccuMed ESP-384 system: the clinical significance of three-day testing

A total of 805 positive blood cultures obtained over a 4-month period during 1997 by the AccuMed ESP-384 system were evaluated and compared with 471 positive blood cultures obtained during 1989. Of the 805 microorganisms isolated in 5-day culture and testing by the ESP-384, 671 (83.4%) were detected within the first 2 days and 758 (94.2%) within 3 days. There were 47 (5.7%) microorganisms detected in culture Days 4 and 5 from 42 patients and review of the medical records from these patients demonstrated that no significant changes in clinical management were instituted as a result of detection and identification of these isolates. These 47 organisms were considered to be zero to equivocal clinical relevance. These data suggest that a 3-day routine blood culture incubation protocol with the ESP-384 system may be sufficient when considering detection rate, clinical relevance, and cost-effectiveness. The microbial spectrum and relative frequencies in this study were found to be similar to those of positive blood cultures obtained during 1989.

In vitro activity of β-lactamase inhibitors against clinical isolates of Acinetobacter species☆

Acinetobacter is an important cause of nosocomial infections, and it is often resistant to many antibiotics. In a search for alternative agents, three beta-lactamase inhibitors (sulbactam, clavulanate, and tazobactam) and five beta-lactam antibiotics (imipenem, ceftazidime, ceftriaxone, cefotaxime, and piperacillin) were tested against 68 unique clinical isolates of Acinetobacter species. Minimum inhibitory concentrations were determined by a broth microdilution method. Using temperature sensitivity testing, we identified 59 strains as Acinetobacter baumannii, one as Acinetobacter haemolyticus, and eight as indeterminate biotype species. We demonstrated 41 of 59 (70%) strains of A. baumannii to be multiply resistant (susceptible only to amikacin and imipenem), whereas all the nonbaumannii strains were not. Imipenem was the most active agent among the compounds investigated. All three beta-lactamase inhibitors had strong intrinsic activity, with sulbactam being the most active agent among the beta-lactamase inhibitors studied.

Comparative susceptibilities of Klebsieila species, Enterobacter species, and Pseudomonas aeruginosa to 11 antimicrobial agents in a tertiary-care university hospital

The in vitro activity of cefepime was compared versus that of 10 antimicrobial agents commonly used in the treatment of serious infections caused by common aerobic gram-negative bacteria: aztreonam, cefoperazone, ceftazidime, ceftriaxone, ciprofloxacin, gentamicin, imipenem, piperacillin, ticarcillin-clavulanic acid, and tobramycin. We tested 30 clinical isolates representing a cross section of Klebsiella and Enterobacter species and Pseudomonas aeruginosa collected at our tertiary-care university hospital. The most potent beta-lactams were imipenem and cefepime, which demonstrated significant activity against the majority of strains in all 3 genera of bacteria tested, as did ciprofloxacin and tobramycin. Ceftazidime was active against Pseudomonas aeruginosa but was less potent against Klebsiella and Enterobacter spp. Cefoperazone and ceftriaxone were less active than ceftazidime against Pseudomonas aeruginosa. Cefepime was found to be highly active against many resistant organisms that traditionally have been difficult to treat.

The detection of positive blood cultures by the bactec NR660 the clinical importance of four-day versus seven-day testing

A total of 471 positive blood cultures obtained over a 3-month period were identified and evaluated for day of positivity by the BACTEC NR660. Of all positive blood cultures, 73% (344) were detected within the first 2 days, and 94% (441) were detected through day 4. The proportion of positive cultures detected at day 5 was significantly lower than that at day 4 (p less than 0.01). Patient chart review revealed that two of 30 isolates (0.4% of all positive isolates) identified on days 5-7 were considered clinically significant and would have been missed if cultures would not have been evaluated for seven days. Therefore, very limited additional patient benefit is derived after greater than 4 days of growth and detection by the BACTEC NR660.