Nontuberculous mycobacterial exit-site infection and abscess in a peritoneal dialysis patient

Nontuberculous mycobacterial infections of peritoneal dialysis catheter exit sites have rarely been reported in patients on peritoneal dialysis. We report here a case of Mycobacterium abscessus exit site infection with abdominal wall abscess formation in an adolescent on peritoneal dialysis, which required long-term antibiotic therapy, peritoneal dialysis catheter removal, and surgical debridement of the abscess. Nontuberculous mycobacteria should be considered as a possible causative organism for an exit site infection that fails to respond to usual antibiotic therapy. Nontuberculous mycobacterial exit site infections may require peritoneal dialysis catheter removal and surgical debridement.     

Drug Susceptibility of Isolates from Severe Postoperative Intraperitoneal Infections Causing Multiple Organ Failure

Purpose To select the most appropriate antibiotic regimens for life-threatening postoperative infections, we obtained isolates from patients with severe postoperative infections over a 12-year-period, and examined their drug susceptibility.Methods The subjects of this study were 55 patients with multiple organ failure (MOF) caused by postoperative infection.Results All strains of Methicillin-resistant Staphylococcus aureus (MRSA) were susceptible to Vancomycin (VCM) and Teicoplanin (TEIC). Only 0.3% of all the Pseudomonas aeruginosa strains were resistant to Imipenem (IPM), but 53.6% of the strains from the severe infections were resistant to IPM. On the other hand, there were few P. aeruginosa strains resistant to Meropenem (MEPM), Ceftazidime (CAZ), Ciprofloxacin (CPFX), and Pazufloxacin (PZFX), even among strains isolated from severe infections. The resistant rate of Bacteroides fragilis to Clindamycin (CLDM) was 35.9%, but there were strains resistant to IPM and Panipenem.Conclusion These findings suggest that VCM or TEIC are most appropriate for severe abdominal abscess caused by MRSA, whereas MEPM, CAZ, CPFX, and PZFX are more effective against P. aeruginosa infections. The only antibiotic effective against B. fragilis infections in this study was IPM.     

Scope and limitations of antimicrobial therapy of sepsis in surgery

Objective: The goal of antibiotic therapy for surgical sepsis is to kill bacteria that intermittently or continuously reach the bloodstream from the residue of an operatively treated focus. While sepsis and conditions leading to sepsis compromise the immune system, antibiotics may become a fundamental determinant of the host's defense. No data from sound prospective randomized clinical antibiotic trials dealing with sepsis are available. Therefore we tested the hypothesis that treatment recommendations can be based on pharmacodynamics comparing in vitro activity of commonly used antimicrobials with concentrations sustained in vivo to provide for full coverage for bacteria of concern. Results: The application of strict criteria for antibiotic choice to avoid selection of primary resistant strains reveals that most commonly used antibiotics render insufficient activity to eliminate pathogens that commonly cause surgical sepsis. Antibiotics that sustain in vivo concentration exceeding fourfold the MIC₁₀₀ (highest minimal inhibitory concentration for all (100%) species tested) of Escherichia coli, for example, are 400 mg ciprofloxacin IV (MIC₁₀₀ of 1224 strains = 0.06 mg/dl, in vivo concentration = 1 mg/dl for 12 h), and 1000 mg imipenem/cilastatin (MIC₁₀₀ of 3142 strains = 0.14 mg/dl, in vivo concentration = 2 mg/dl for 6 h). The third choice is one of the fourth- or, less convincingly, third-generation cephalosporins. Similar data for most pathogens causing sepsis are provided. First- and second-generation cephalosporins and penicillin β-lactamase inhibitor combinations generally do not achieve sufficient concentrations to cover the most important pathogens of sepsis. Conclusion: Sepsis is defined as a whole body's inflammatory response that is characterized by systemic signs and symptoms secondary to a focal infection. While many antibiotic trials have dealt with a focal infection, no prospective randomized antibiotic trial has dealt with sepsis per se. Antibiotic trials on focal infections generally exclude patients when their focal infection has progressed to sepsis. To circumvent the lack of controlled clinical trials we show that pharmacodynamics may provide sound foundation for antibiotic choice for sepsis. Received: 10 December 1997     

Teicoplanin in the prevention of infection in total hip replacement

Perioperative antibiotic prophylaxis has been shown to be effective in reducing postoperative wound infections. The rising incidence of infections secondary to methicillin-resistant strains of Staphylococcus aureus, S. epidermidis and S. enterococcal prompted us to administer Teicoplanin to infection in elective total joint arthroplasty. In 111 patients Teicoplanin was given in a single intravenous dose of 10 mg/kg prior to surgery. In the postoperative period no deep infection of the prosthetic device was found in a 14-month follow-up. In two patients the following organisms were isolated from superficial infections of the wound: S. epidermidis (methicillin-sensitive), Pseudomonas aeruginosa, and Enterobacter sp. In no patient was revision surgery necessary. The serum concentration of Teicoplanin was within the therapeutic range during surgery, and tissue levels of Teicoplanin in cancellous (6.2 mg/kg, range 3.8-10.9 mg/kg) and cortical (7.1 mg/kg, range 2.6-12.1 mg/kg) bone during surgery in 16 patients exceeded the minimum inhibitory concentration of 90% (MIC₉₀) of methicillin-resistant strains reported for methicillin-resistant strains. In our experience a single dose regimen of Teicoplanin is a safe and effective method of antibiotic prophylaxis in hip joint replacement, particularly when methicillin-resistant bacteria are present.     

Febrile urinary tract infection in children: ampicillin and trimethoprim insufficient as empirical mono-therapy

The aim of this study was to characterize the pathogens and their antibiotic susceptibilities in defined groups of children (total number 694) with urinary tract infection (UTI) regarding age, first UTI (FUTI) or recurrent UTI (RUTI), renal abnormalities or vesico-ureteric reflux (VUR) in order to optimize empirical antibiotic therapy and prophylaxis. In patients aged between 1 month and 24 months with a first febrile UTI (FUTI; n = 205) the leading pathogen was Escherichia coli (E. coli) (83.4%). In comparison with patients with FUTI, those with RUTI (n = 24) had more Enterococcus and Enterobacter infections and higher resistance rates of E. coli against trimethoprim (TMP), trimethoprim/sulfamethoxazole (SXT) or ampicillin (AMP). Boys with ultrasound-detected renal abnormalities (n = 71) showed 14.2% Pseudomonas and 59.1% E. coli infections versus girls (n = 48) (2.1% Pseudomonas and 93.7% E. coli). Of 390 patients who underwent voiding cysto-urethrography, 31.5% had VUR. Of them, 45.5% received antimicrobial prophylaxis with SXT (n = 30) or cefazolin (n = 26). There was no difference between girls (n = 242) and boys (n = 148) regarding the frequency of VUR and pathogens. There were more TMP- and SXT-resistant E. coli cultures from patients with VUR (37.8%) than from those without VUR (25.8%). Treatment with TMP, SXT and AMP alone appeared to be insufficient in many cases because of high resistance rates of E. coli and other uropathogens.     

One time quantitative PCR detection of Pseudomonas aeruginosa to discriminate intermittent from chronic infection in cystic fibrosis

Background

Chronic airway infection with Pseudomonas aeruginosa is a major risk factor of progression of lung disease in patients with cystic fibrosis (CF). Chronic P. aeruginosa infection evolves from intermittent infection that is amenable to antibiotic eradication, whereas chronically adapted P. aeruginosa becomes resistant to antibiotic therapy. Discrimination of intermittent versus chronic infection is therefore of high therapeutic relevance, yet the available diagnostic methods are only partly satisfactory. The aim of the present study was, therefore, to evaluate the usage of quantitative PCR (qPCR) to measure pathogen abundance and to discriminate between intermittent and chronic Pseudomonas infection in patients with CF.

An additional dose of cefazolin for intraoperative prophylaxis

We examined the pancreatic tissue concentrations of cefazolin in ten patients undergoing pancreatectomy, and determined the optimal intraoperative time to deliver a repeat dose of cefazolin. An intravenous bolus dose of 1 g cefazolin was administered at the time of skin incision. Peripheral blood, subcutaneous adipose tissue, and peritoneal samples were obtained intraoperatively every hour for 4h after the antibiotic was first administered, and pancreatic tissue samples were obtained at the time of pancreatectomy. To determine adquate tissue levels of cefazolin, minimum inhibitory concentrations (MIC) were measured for four bacterial species, namely 360 isolates of methicillin-sensitiveStaphylococcus aureus (MSSA), 204 isolates ofKlebsiella pneumoniae, 314 isolates ofEscherichia coli, and 30 isolates ofStreptococcus spp. The antibiotic concentrations in adipose tissue and peritoneum 3 h after the administration of cefazolin were lower than the MIC₈₀ forK. pneumoniae, E. coli, andStreptococcus spp. Most pancreatic tissue samples showed antibiotic concentrations greater than the MIC₈₀ for these bacterial species; however, those from four patients complicated by severe chronic pancreatitis, massive intraoperative bleeding, or obesity showed concentrations lower than the MIC₈₀. Thus, we recommend that a second dose of cefazolin be given 3 h after thefirst administration to maintain adequate levels of antibiotic activity.     

Catheter revision for the treatment of intractable exit site infection/tunnel infection in peritoneal dialysis patients: A single centre experience

Aim: Catheter‐related infection is a major cause of catheter loss in peritoneal dialysis (PD). We evaluated the effect of catheter revision on the treatment of intractable exit site infection (ESI)/tunnel infection (TI) in PD patients who required catheter removal. Methods: We reviewed the medical records of 764 continuous ambulatory peritoneal dialysis (CAPD) patients from May 1995 to April 2011 at our hospital. One hundred and twenty six patients had more than one occurrence of ESI. Catheter revision was performed to treat intractable ESI/TI. Incidence of ESI, causative organisms and the outcomes of catheter revision were analyzed. Results: The total PD duration of all patients was 32 581 months. Three hundred and twelve ESI episodes occurred in 126 patients and the incidence of ESI was 1/104 patient‐months (0.12/patient‐year). The most common causative organism was methicillin‐sensitive Staphylococcus aureus (MSSA) (98 episodes), followed by Pseudomonas aeruginosa (63 episodes) and methicillin‐resistant S. aureus (MRSA) (28 episodes). Among these, catheter revision was required due to intractable ESI/TI in 36 patients. The most common causative organism was MSSA (14 episodes) followed by P. aeruginosa (10 episodes) and MRSA (six episodes) in catheter revision cases. The outcomes of catheter revision were as follows: ESI relapsed in 11 patients (30.6%) after catheter revision. Among them, five patients were treated with antibiotic treatment, two patients required secondary catheter revision, four patients required catheter removal due to ESI/TI accompanying peritonitis. The catheter survival rate after catheter revision was 89.7% in one year. There were no statistical differences in the rates of ESI relapse after catheter revision between ESI caused by P. aeruginosa (5/10, 50%) and ESI caused by S. aureus (6/21, 28.6%). Conclusion: Catheter revision may be an alternative treatment option to treat intractable ESI/TI before catheter removal is considered in PD patients.     

Untersuchungen zum Empfindlichkeitsspektrum von Framycetin Vergleich der Resistenzsituation von 1972 bis 1993

Zusammenfassung Anhand eines Kollektivs frisch isolierter St?mme von grampositiven und gramnegativen Bakterien zeigt Framycetin auch heute noch eine gute In-vitro-Aktivit?t gegenüberStaphylococcus aureus, Staphylococcus epidermidis, Enterobacteriaceaen sowiePseudomonas aeruginosa undPseudomonas fluorescens.

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Studies of sensitivity pattern of framycetin. Comparison of the resistance situation in 1972 to 1993

Framycetin was tested against a variety of isolates of grampositive and gramnegative bacteria. The in-vitro activity of Framycetin againstStaphylococcus aureus, Enterobacteriaceae,Pseudomonas aeruginosa as well asPseudomonas fluorescens is tody still favourable.

     

The role of prophylactic antibiotics in elective inguinal tension-free hernia repair: A systematic review and meta-analysis

Whether to use antibiotics to prevent surgical site infection in elective inguinal tension-free hernia repair has been controversial. To systematically evaluate the effect of prophylactic antibiotic application in elective inguinal tension-free hernia repair, we identified all published randomised controlled trials of the effect of prophylactic antibiotic application on elective inguinal tension-free hernia repair were collected by computer retrieval from the China National Knowledge Infrastructure; VIP Database; Wanfang Database; China Biomedical Literature Database; and PubMed, EMBASE and Cochrane Library databases. Meta-analysis was performed by RevMan 5.3 software. The meta-analysis showed that the total incidence of surgical site infections [P = 0.003] and the incidence of superficial surgical site infections [P = 0.004] in the antibiotic group (AG) were lower than those in the non-antibiotic group (NAG). There was no significant difference in the total incidence of postoperative infections [P = 0.06], deep surgical site infections [P = 0.26] and seroma [P = 0.52] between the AG and the NAG. Based on current evidence, the application of prophylactic antibiotics in elective inguinal tension-free hernia repair can prevent the total incidence of surgical site infections and that of superficial surgical site infections but cannot prevent the total incidence of postoperative infection events, incidence of deep surgical site infections and incidence of seroma.     

Quantifying infection risks in incompatible living donor kidney transplant recipients

Desensitization has enabled incompatible living donor kidney transplantation (ILDKT) across HLA/ABO barriers, but added immunomodulation might put patients at increased risk of infections. We studied 475 recipients from our center from 2010 to 2015, categorized by desensitization intensity: none/compatible (n = 260), low (0-4 plasmaphereses, n = 47), moderate (5-9, n = 74), and high (≥10, n = 94). The 1-year cumulative incidence of infection was 50.1%, 49.8%, 66.0%, and 73.5% for recipients who received none, low, moderate, and high-intensity desensitization (P < .001). The most common infections were UTI (33.5% of ILDKT vs. 21.5% compatible), opportunistic (21.9% vs. 10.8%), and bloodstream (19.1% vs. 5.4%) (P < .001). In weighted models, a trend toward increased risk was seen in low (wIRR = _0.771.40_2.56,P = .3) and moderately (wIRR = _0.881.35_2.06,P = .2) desensitized recipients, with a statistically significant 2.22-fold (wIRR = _1.332.22_3.72,P = .002) increased risk in highly desensitized recipients. Recipients with ≥4 infections were at higher risk of prolonged hospitalization (wIRR = _2.623.57_4.88, P < .001) and death-censored graft loss (wHR = _1.154.01_13.95,P = .03). Post–KT infections are more common in desensitized ILDKT recipients. A subset of highly desensitized patients is at ultra-high risk for infections. Strategies should be designed to protect patients from the morbidity of recurrent infections, and to extend the survival benefit of ILDKT across the spectrum of recipients.     

Reducing surgical site infections through a multidisciplinary computerized process for preoperative prophylactic antibiotic administration

Background

Surgical site infections (SSIs) result in significant postoperative morbidity and mortality. Although many of these infections can be prevented by timely administration of preoperative antibiotics, data suggest that many patients do not receive such therapy.

Methods

A multidisciplinary team was convened that reviewed published guidelines, made antibiotic recommendations, and addressed administration issues. Responsibility for antibiotic administration was shifted from preoperative nursing staff to the anesthetist. Electronic quick orders were developed to encourage appropriate antibiotic selection and simplify order creation.

Results

Timely administration of preoperative antibiotics improved from 51% to 98% from February 2005 to February 2006. Appropriate antibiotic administered improved from 78% to 94%. The clean wound infection rate decreased from 2.7% to 1.4% over the same time period.

Conclusion

A multidisciplinary approach to prophylactic antibiotic use, including computer-guided decision support, facilitates appropriate preoperative antibiotic use, resulting in a significant decrease in surgical wound infections.     

The influence of clinical use of antibiotics on the sensitivity of strains isolated from postoperative infections —A comparison of nosocomial pathogens with strains isolated from the bacterial flora of patients—

In the present study, we investigated how the recent clinical use of antibiotics have altered the antibiotic susceptibility of strains isolated from postoperative infections, especially Gram-negative rods. ForPseudomonas aeruginosa, serogroup E strains acounted for about 20 per cent of postoperative infections, but were unable to the isolated from either the feces of patients on admission or from the appendix contents of patients with appendicitis. It therefore appeared that serogroup E strains were responsible for the nosocomial infections in our department. The strains of methicillin-resistantStaphylococcus aureus andPseudomonas aeruginosa serogroup E, which we assumed to be nosocomial pathogens, acquired a high level of resistance to antibiotics soon after third-generation cephems became widely used. On the other hand, the antibiotic susceptibility ofEnterobacter cloacae, Citrobacter freundii, and the serogroups ofPseudomonas aeruginosa other than E, which were considered to originate from the bacterial flora of patients, did not vary throughout the several years of the study period.     

Infection after transrectal ultrasonography-guided prostate biopsy: increased relative risks after recent international travel or antibiotic use

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Septicaemia is the most frequent cause of hospitalization after transtrectal prostate biopsy; fatalities have been reported and the incidence is on the rise. This study shows that men with a history of recent international travel or antibiotic use have up to four times increased risk of septicaemia and hospitalization. When they do occur, infections are usually due to multi‐resistant E coli and additional care, e.g. delay before biopsy, different antibiotic prophylaxis or transperineal biopsy, should be considered in these cases. OBJECTIVE

• ? To study the infection rate after prostate biopsy in those who have travelled overseas or used antibiotics in the 4 weeks before biopsy.

PATIENTS AND METHODS

• ? A total of 316 men with a mean (range) age of 61 (45–85) years were studied. All had undergone transrectal ultrasonography (TRUS)‐guided prostate biopsy after standard antibiotic prophylaxis.
• ? Before their biopsy the patients were risk stratified and a history of recent international travel or antibiotic use was recorded.
• ? Those who suffered sufficiently severe infection/sepsis so as to require hospitalization were identified at the end of the study period.
• ? The characteristics of these patients and the types of infections were explored and the relative risk (RR) of infection after recent travel or antibiotic use was calculated.

RESULTS

• ? Of the 316 men, 16 were hospitalized with infection.
• ? The group with (n= 16) and without (n= 300) infection were equivalent in age, prostate‐specific antigen level, disease status and number of biopsy cores taken.
• ? Either recent travel or antibiotic use were independent risk factors for infection [travel: 8/16 vs 76/300; P= 0.04; RR 2.7 and antibiotic use: 4/16 vs 20/300; P= 0.025; RR 4]. There was no significant pattern in the countries visited or the type of antibiotic used.
• ? Culture results were positive in 10/16 men, and all cultures grew multiresistant Escherichia coli. The strains were uniformly resistant to ciprofloxacin and amoxycillin, and variably resistant to gentamicin and co‐amoxiclav, but nearly all were sensitive to meropenem.
• ? All patients made a full recovery after antibiotic and supportive treatment.

CONCLUSIONS

• ? Either recent international travel or antibiotic use are independent risk factors for severe infection after TRUS‐guided prostate biopsy.
• ? When infection does occur it should be treated aggressively as the causative agent is usually a multiresistant E. coli.

     

Closed‐incision negative pressure therapy to reduce groin wound infections in vascular surgery: a randomised controlled trial

Groin wound infections pose a major problem in vascular surgery. Closed‐incision negative pressure therapy (ciNPT) was especially designed for the management of incisions at risk of surgical site infections. The aim of this study was to investigate whether ciNPT is able to reduce the incidence of wound infections after vascular surgery. Data on 132 consecutive patients, scheduled for vascular surgery with a longitudinal femoral cutdown, were collected prospectively. All patients were randomised either to the ciNPT group (n = 64) or the control group (n = 68) with conventional dressing. In the ciNPT group, the foam dressing was applied intraoperatively and removed after 5 days. The control group received an absorbent dressing. All wounds were evaluated after 5 and 42 days. Infections were graded according the Szilagyi classification (I–III°). There were no significant differences between both groups considering patient characteristics. Indications for surgery were peripheral arterial disease in 95% (125/132) and aneurysm in 5% (7/132). The overall infection rates were 14% (9/64) in the ciNPT group and 28% (19/68) in the control group (P = 0·055). Early infections were observed in 6% (4/64) of the ciNPT group and 15% (10/68) of the control group (P = 0·125). ciNPT did not reduce infection rates associated with different risk factors for infection. While the experiences with the ciNPT device were encouraging, the study fails to provide evidence of the efficacy of the device to reduce groin wound infections after vascular surgery. It illustrates far more that larger multicentre studies are required and appear promising to provide further evidence for the use of ciNPT.     

Management of bacterial peritonitis and exit‐site infections in continuous ambulatory peritoneal dialysis*

SUMMARY: Peritonitis and exit‐site infections remain the most important limitations to the delivery of continuous ambulatory peritoneal dialysis (CAPD). Contamination of the peritoneum, from endogenous or exogenous sources, is responsible for most peritonitis episodes. Patients usually present with a cloudy bag, although other causes should be distinguished. Clinical suspicion of peritonitis should be followed rapidly by microbiological examination and empirical treatment. Microbiological confirmation allows for subsequent treatment based on sensitivities. Other interventions such as catheter removal may be appropriate in some patients. Exit‐site infections should also be identified and treated early. Peritonitis may be further prevented by adequate exit‐site care, hygienic methods, and techniques to minimise early contamination of the exit site. Mupirocin may also have a role in preventing infections caused by Staphylococcus aureus.     

The clinical course of rapidly growing nontuberculous mycobacterial peritoneal dialysis infections in Asians: A case series and literature review

Introduction: Peritoneal dialysis (PD)‐related infections due to rapidly growing nontuberculous mycobacterium (RGNTM) are rare in Asians and have variable clinical outcomes. Methods: We analysed retrospectively a series of RGNTM infections in a single‐centre multi‐ethnic Asian population over a 5‐year period. Clinical features, treatment, risk factors and outcomes are discussed. Results: Ten infections are described. They constituted 3% of all culture‐positive exit site infection (ESI) and PD peritonitis. Seventy percent were due to Mycobacterium abscessus (three ESI and four peritonitis). There were two Mycobacterim fortuitum and one Mycobacterium chelonei peritonitis. No specific findings differentiated RGNTM infections from those caused by traditional organisms. Six cases had received prior antibiotics, two being topical gentamicin. Initial routine culture and alcohol acid fast bacillus were negative except for one case of M. abscessus. A confirmatory diagnosis was made a median 9 days post culture. No infection responded to routine antibiotics. Antibiotic resistance was variable but M. abscessus was universally sensitive to clarithromycin. Combined antibiotics based on sensitivity profile were successfully used in 70% of the cases. PD catheter loss was 80%. Three‐month mortality was 40% (vs. 8.5% and 12% in non‐RGNTM ESI and peritonitis, respectively). This may be related to the cohort high mean Charlson score of 7.5. Conclusion: RGNTM PD infections are commoner in Asians than previously reported. Their early diagnosis requires a high index of suspicion and appropriate treatment started promptly. They are associated with prior antibiotic use and refractory culture‐negative infections, delayed diagnosis and lead to significant catheter loss and death.     

Clinico‐microbiological study of Pseudomonas aeruginosa in wound infections and the detection of metallo‐β‐lactamase production

Pseudomonas aeruginosa is a common opportunistic pathogen of humans among the Gram‐negative bacilli. Clinically, it is associated with nosocomial infections like burns and surgical‐site wound infections and remains a major health concern, especially among critically ill and immunocompromised patients. This is a prospective laboratory‐based 2 year study conducted to isolate P. aeruginosa from wound specimens and the antimicrobial susceptibility pattern with reference to metallo‐β‐lactamase (MBL) production. Two hundred and twenty‐four samples of P. aeruginosa isolated from wound specimens were included in the study. Antimicrobial susceptibility was done as per Clinical Laboratory Standard Institute (CLSI) guidelines. MBL‐producing P. aeruginosa was detected using the EDTA disk diffusion synergy test. Statistical analysis was done using the SPSS 11 package (SPSS Inc., Chicago, IL). Out of the 224 P. aeruginosa isolates, 100% were susceptible to polymyxin B and colistin, 92·8% were sensitive to imipenem, 38% showed resistance to gentamicin followed by ceftazidime (31·69%) and meropenem (33·03). Sixteen (7·14%) isolates showed MBL production. Infection caused by drug‐resistant P. aeruginosa is important to identify as it poses a therapeutic problem and is also a serious concern for infection control management. The acquired resistance genes can be horizontally transferred to other pathogens or commensals if aseptic procedures are not followed.     

Antibiotic resistance in clinical isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus does not impact sensitivity to human beta defensin 4

Antibiotic usage is essential for infection control but hastens emergence of antibiotic resistant microbes. In particular, Acinetobacter baumannii is an important pathogen because of its heightened ability to acquire drug resistance. The need for novel antibacterial agents led us to evaluate the sensitivity of drug-resistant bacteria to the antimicrobial activity of human beta defensin 4 (HBD-4). Clinical isolates of A. baumannii (N = 14), Pseudomonas aeruginosa (N = 15), and Staphylococcus aureus (N = 20), including 10 methicillin-resistant (MRSA) isolates, were examined. All bacterial strains were susceptible to HBD-4 antimicrobial activity, with no correlation between antibiotic resistance and HBD-4 sensitivity. The results demonstrate that antibiotic resistant microorganisms, including MRSA, can be inhibited by HBD-4, which may represent an effective therapeutic agent for infections involving drug-resistant microorganisms.     

Protective role of Coenzyme Q10 in two models of rat lung injury

Background: Ischaemia‐reperfusion injury is a life‐threatening complication of lung transplantation. Attempts to ameliorate this injury have included optimization of donor management and improving techniques of lung preservation. However, few investigators have sought to pretreat potential recipients. Coenzyme Q₁₀ (CoQ₁₀) is a potent antioxidant and cellular energizer that has been shown to protect the heart against injury. However, its protective effect in the lung is unknown. We therefore set out to study the impact of Coenzyme Q₁₀ pretreatment in a model of mild and severe lung injury. Methods: We evaluated the impact of CoQ₁₀ in a two‐stage laboratory study. In the first stage, in order to measure the magnitude of increase in tissue and plasma CoQ₁₀ following oral therapy we administered high‐dose oral CoQ₁₀ to rats (n = 6). In the second stage we evaluated the impact of CoQ₁₀ in the rat lung (n = 10) that was subjected to 230 min of normoxic lung injury or 90 min of warm ischaemia and 120 min of reperfusion in a model of lung transplantation. Results: High‐dose oral CoQ₁₀ for 7 days produced a 15‐fold increase in plasma and a 3‐fold increase in lung CoQ₁₀. In the normoxic lung, the injury‐induced rise in peak airway pressure was reduced by CoQ₁₀ treatment at 90 min (P = 0.037) and at 120 min (P = 0.005) without any change in arterial oxygen. In the lung subjected to severe ischaemia‐reperfusion injury, CoQ₁₀ did not reduce the injury‐induced increase in peak airway pressure (P = 0.599) nor the decrease in arterial oxygen (P = 0.844). However, CoQ₁₀ markedly reduced the increase in tumour necrosis factor‐alpha in ischaemic compared with normoxic lung (P = 0.027). Conclusions: The effect of CoQ₁₀ pretreatment is insufficient to protect the lung against severe ischaemia‐reperfusion as may occur in lung transplantation. However, in the setting of less severe pulmonary injury as in anaesthesia and non‐transplant surgery, CoQ₁₀ may have a protective role.