Effect of early directed implementation of family-integrated care measures on colonisation with Enterobacteriaceae in preterm neonates in NICU.

BACKGROUND: Hospital-acquired strains (HASs) and multiresistant strains in neonatal intensive care unit often harbour virulence and resistance mechanisms, carrying the risk of invasive infections. We describe colonisation with Enterobacteriaceae in neonates receiving early directed versus routine family-integrated care (FIC) within the first month of life. METHODS: A prospective cohort study included neonates with a gestational age below 34 weeks. During the first period, neonates were admitted to an open bay unit with transfer to the single-family room if available; feeding with the mother's own breast milk (MOBM) was introduced within 24 hours, and skin-to-skin contact (SSC) within 5 days of life (the routine care group). During the second period, following a wash-in of 2 months, care in a single-family room within 48 hours, the introduction of MOBM within two and SSC in 48 hours were applied (the intervention group). Enterobacteriaceae isolated from neonatal stool, breast milk and parental skin swabs were genotyped, Simpson's Index of Diversity (SID) calculated, and extended-spectrum beta-lactamases (ESBL) detected. RESULTS: In 64 neonate-parents' groups, 176 Enterobacteriaceae, 87 in routine care and 89 in the intervention group were isolated; 26 vs 18 were HAS and one vs three ESBL positive, respectively. In the intervention group compared with the routine care group, SSC and MOBM feeding was started significantly earlier (p<0.001); during the first week of life, time spent in SSC was longer (median hours per day 4.8 (4-5.1) vs 1.9 (1.4-2.6), p<0.001) and the proportion of MOBM in enteral feeds was higher (median (IQR) 97.8% (95.1-100) vs 95.1% (87.2-97.4), p=0.011). Compared with the routine care group, the intervention group had higher SID and a reduction of HAS by 33.1% (95% CI 24.4% to 42.4%) in time series analysis. CONCLUSIONS: Early implementation of FIC measures may hold the potential to increase diversity and reduce colonisation with HAS Enterobacteriaceae.

Ceftazidime-Avibactam To Treat Life-Threatening Infections by Carbapenem-Resistant Pathogens in Critically Ill Mechanically Ventilated Patients.

Data on the effectiveness of ceftazidime-avibactam (CAZ-AVI) in critically ill, mechanically ventilated patients are limited. The present retrospective observational cohort study, which was conducted in two general intensive care units (ICUs) in central Greece, compared critically ill, mechanically ventilated patients suffering from carbapenem-resistant Enterobacteriaceae (CRE) infections receiving CAZ-AVI to patients who received appropriate available antibiotic therapy. Clinical and microbiological outcomes and safety issues were evaluated. A secondary analysis in patients with bloodstream infections (BSIs) was conducted. Forty-one patients that received CAZ-AVI (the CAZ-AVI group) were compared to 36 patients that received antibiotics other than CAZ-AVI (the control group). There was a significant improvement in the Sequential Organ Failure Assessment (SOFA) score on days 4 and 10 in the CAZ-AVI group compared to that in the control group (P = 0.006, and P = 0.003, respectively). Microbiological eradication was accomplished in 33/35 (94.3%) patients in the CAZ-AVI group and 21/31 (67.7%) patients in the control group (P = 0.021), and clinical cure was observed in 33/41 (80.5%) versus 19/36 (52.8%) patients (P = 0.010), respectively. The results were similar in the BSI subgroups for both outcomes (P = 0.038 and P = 0.014, respectively). The 28-day survival was 85.4% in the CAZ-AVI group and 61.1% in the control group (log-rank test = 0.035), while there were 2 and 12 relapses in the CAZ-AVI and control groups, respectively (P = 0.042). A CAZ-AVI-containing regime was an independent predictor of survival and clinical cure (odds ratio [OR] = 5.575 and P = 0.012 and OR = 5.125 and P = 0.004, respectively), as was illness severity. No significant side effects were recorded. In conclusion, a CAZ-AVI-containing regime was more effective than other available antibiotic agents for the treatment of CRE infections in the high-risk, mechanically ventilated ICU population evaluated.

Considerations for Systemic and Topical Treatment of Morganella morganii Septicemia Arising from Maggot Infestation.

INTRODUCTION: Live maggot infestation (myiasis) of wounds can present a host of ailments. Loosely associated with maggot excreta, Morganella morganii is a widespread, gram-negative rod bacterium commonly found in the intestinal tracts of humans. M morganii has been observed as being pathogenic, particularly in nosocomial and postoperative environments, as well as in immunosuppressed and elderly populations. CASE REPORT: Herein, the authors present a rare, previously unreported case of M morganii septicemia (as confirmed by positive blood culture), secondary to myiasis of the lower extremities. The patient was successfully treated with both systemic and topical interventions. Posttreatment examination revealed resolution of myiasis and negative blood cultures. CONCLUSIONS: Myiasis can be invasive, leading to severe systemic infection. In these cases, a broad-spectrum antibiotic combined with systemic and topical antiparasitic therapy should be considered.

A Lytic Providencia rettgeri Virus of Potential Therapeutic Value Is a Deep-Branching Member of the T5virus Genus.

Providencia rettgeri is emerging as a new opportunistic pathogen with high antibiotic resistance. The need to find alternative methods to control antibiotic-resistant bacteria and the recent advances in phage therapy motivate the search for new phages able to infect Providencia spp. This study describes the isolation and characterization of an obligatory lytic phage, vB_PreS_PR1 (PR1), with therapeutic potential against drug-resistant P. rettgeri PR1 is a siphovirus. Its virion DNA size (118,537 bp), transcriptional organization, terminal repeats (10,461 bp), and nicks in the 3'-to-5' strand are similar to those of phage T5. However, sequence similarities of PR1 to phages of the T5virus genus at the DNA and protein levels are limited, suggesting that it belongs to a new species within the Siphoviridae family. PR1 exhibits the ability to kill P. rettgeri antibiotic-resistant strains, is highly specific to the species, and did not present known genomic markers indicating a temperate lifestyle. The lack of homologies between its proteins and proteins of the only other sequenced Providencia prophage, Redjac, suggests that these two phages evolved separately and may target different host proteins.IMPORTANCE The alarming increase in the number of bacteria resistant to antibiotics has been observed worldwide. This is particularly true for Gram-negative bacteria. For certain of their strains, no effective antibiotics are available. Providencia sp. has been a neglected pathogen but is emerging as a multidrug-resistant bacterium. This has revived interest in bacteriophages as alternative therapeutic agents against this bacterium. We describe the morphological, physiological, and genomic characterization of a novel lytic virus, PR1, which is able to kill drug-resistant P. rettgeri clinical isolates. Genomic and phylogenetic analyses indicate that PR1 is a distant relative of T5virus genus representatives. The lack of known virulence- or temperate lifestyle-associated genes in the genome of PR1 makes this phage a potential candidate for therapeutic use. Analysis of its genome also improves our knowledge of the ecology and diversity of T5-like siphoviruses, providing a new link for evolutionary studies of this phage group.

Bacteriophage therapy against Enterobacteriaceae.

The Enterobacteriaceae are a class of gram-negative facultative anaerobic rods, which can cause a variety of diseases, such as bacteremia, septic arthritis, endocarditis, osteomyelitis, lower respiratory tract infections, skin and soft-tissue infections, urinary tract infections, intra-abdominal infections and ophthalmic infections, in humans, poultry, animals and fish. Disease caused by Enterobacteriaceae cause the deaths of millions of people every year, resulting in enormous economic loss. Drug treatment is a useful and efficient way to control Enterobacteriaceae infections. However, with the abuse of antibiotics, drug resistance has been found in growing number of Enterobacteriaceae infections and, as such, there is an urgent need to find new methods of control. Bacteriophage therapy is an efficient alternative to antibiotics as it employs a different antibacterial mechanism. This paper summarizes the history of bacteriophage therapy, its bacterial lytic mechanisms, and the studies that have focused on Enterobacteriaceae and bacteriophage therapy.

Efficiency of bacteriophage therapy against Cronobacter sakazakii in Galleria mellonella (greater wax moth) larvae.

Cronobacter sakazakii, an opportunistic pathogen found in milk-based powdered infant formulae, has been linked to meningitis in infants, with high fatality rates. A set of phages from various environments were purified and tested in vitro against strains of C. sakazakii. Based on host range and lytic activity, the T4-like phage vB_CsaM_GAP161, which belongs to the family Myoviridae, was selected for evaluation of its efficacy against C. sakazakii. Galleria mellonella larvae were used as a whole-animal model for pre-clinical testing of phage efficiency. Twenty-one Cronobacter strains were evaluated for lethality in G. mellonella larvae. Different strains of C. sakazakii caused 0 to 98% mortality. C. sakazakii 3253, with an LD50 dose of ~2.0×10(5) CFU/larva (24 h, 37 °C) was selected for this study. Larvae infected with a dose of 5×LD50 were treated with phage GAP161 (MOI=8) at various time intervals. The mortality rates were as high as 100% in the groups injected with bacteria only, compared to 16.6% in the group infected with bacteria and treated with phage. Phage GAP161 showed the best protective activity against C. sakazakii when the larvae were treated prior to or immediately after infection. The results obtained with heat-inactivated phage proved that the survival of the larvae is not due to host immune stimulation. These results suggest that phage GAP161 is potentially a useful control agent against C. sakazakii. In addition, G. mellonella may be a useful whole-animal model for pre-screening phages for efficacy and safety prior to clinical evaluation in mammalian models.

Non-surgical management of thyroid abscess with ultrasound-guided fine-needle application of an antibiotic followed by sclerotization with absolute alcohol.

Thyroid abscess is a relatively rare yet dramatic condition of the thyroid gland requiring immediate therapeutic intervention. Traditionally, more or less aggressive surgical approaches and administration of broad-spectrum antibiotics have been used. Clinically less severe disease allows non-surgical treatment as well. The case report describes successful treatment of a large abscess of iatrogenic origin after biopsy of a cystic cavity. A combination of broad-spectrum antibiotics was used based on culture results, administered both orally and by repeated application directly into the abscess cavity using an ultrasound-guided fine-needle approach. Concurrent repeated evacuation of the cavity replaced drainage. Ultimately, a small residual cavity with sterile contents was managed by sclerotization with absolute alcohol. Clinical condition permitting, thyroid abscess may be successfully treated by repeated application of a targeted antibiotic, using a fine needle and ultrasound guidance, directly into the abscess cavity, with repeated evacuation replacing drainage.

Early diagnosis and treatment of necrotizing fasciitis can improve survival: an observational intensive care unit cohort study.

BACKGROUND: The aim of this study was to describe the clinical characteristics, causative pathogens, clinical management and outcomes of patients presenting to a tertiary adult Australian intensive care unit (ICU) with a diagnosis of necrotizing fasciitis (NF). METHODS: This retrospective observational study was conducted in a 19-bed, level III, adult ICU in a 450-bed tertiary, regional hospital. Clinical databases were accessed for patients diagnosed with NF and admitted to The Geelong Hospital ICU between 1 February 2000 and 1 June 2011. Information on severity of sepsis, surgical procedures and microbiological results were collected. RESULTS: Twenty patients with NF were identified. The median age was 52.5 years and 38% were female. The overall mortality rate was 8.3%. Common co-morbidities were diabetes (21%) and heart failure (17%), although 50% of patients had no co-morbidities. Group A Streptococcus was the identified pathogen in 11 (46%) patients, and Streptococcus milleri group in 5 (21%) patients. Hyperbaric oxygen therapy was not used in the majority of patients. The initial antibiotics administered were active against subsequently cultured bacteria in 83% of patients. Median time to surgical debridement was 20 h. Diagnosis and management was delayed in the nosocomial group. CONCLUSIONS: This study reports physiological data, aetiology and therapeutic interventions in NF for an adult tertiary hospital. We demonstrate one of the lowest reported mortality rates, with early surgical debridement being achieved in the majority of patients. The main delay was found to be in the diagnosis of NF.

New Delhi Metallo-beta lactamase-1 containing enterobacteriaceae: origin, diagnosis, treatment and public health concern.

One of the biggest problems associated with the antibiotic therapy is resistance. Recently published studies have revealed that enterobacteriaceae, like E. coli and Klebsiella, isolated from several Indian centers are resistant to many antibiotics including some highly potent antibiotics like carbapenems. It has been proposed that this resistance is because of a carbapenemase enzyme called NDM-1 (New Delhi Metallo-betalactamase-1). This carbapenemase is class B carbapenemase also called metallolactamases as they require zinc at their active site. This enzyme is coded by a gene called bla-NDM-1 or gene NDM-1. NDM-1 containing enterobacteriaceae can be screened in laboratory by few techniques. Metallolactamase production can be detected by disk approximation test or Modified Hodge test and NDM-1 gene can be detected by polymerase chain reaction by the use of specific primer targeting the gene. Infections caused by such bacteria are associated with high morbidity and mortality. Two classes of antibiotics i.e., polymyxins (colistin) and glycylcyclines (tigecyclines), have shown in vitro activity against NDM-1 harboring enterobacteriaceae. The safety profile of both of these antibiotics is questionable. There is a need for active screening of microorganisms for NDM-1 and research should be directed towards the development of safe antibiotics for the treatment of these kinds of infections.

Prevalence of silver resistance in bacteria isolated from diabetic foot ulcers and efficacy of silver-containing wound dressings.

Silver dressings are used to manage wounds at risk of infection or locally infected. This in vitro study was conducted to assess the prevalence of silver resistance genes in 112 bacterial isolates obtained from the diabetic foot ulcers of patients attending the Diabetic Foot Clinic at Tameside General Hospital, UK. Using polymerase chain reaction to screen for three silver-resistance transcriptional units--silE, silS and silP--two silver-resistant bacteria were identified; both are strains of Enterobacter cloacae, an organism rarely implicated as a primary pathogen in chronic wounds. No recognized wound pathogens (Staphylococcus aureus-24 isolates and Pseudomonas aeruginosa-nine isolates) were found to contain silver-resistant genes. Analysis of the efficacy of silver-containing dressings on the silver-resistant strains of Enterobacter cloacae using confocal laser microscopy showed that, despite evidence of genetic resistance to silver, all strains were killed following a maximum of 48 hours of exposure to the dressings. Results suggest that presence of silver resistance genes is rare and that genetic resistance does not necessarily translate to phenotypic resistance to silver. While silver resistance in wound care should be monitored, the threat of widespread resistance is low and silver-containing dressings remain an extremely important tool in managing wound infection.

[Maggot therapy for treatment of severe infections in trauma surgery: "back to the future!"]. / Maden: Ein neues Konzept in der Behandlung von Infektionen in der Traumatologie -- "Back to the Future!"

The ancient method of larval therapy for treatment of acute and chronic infections has become a revival and a new dimension with introduction of the Biobag (Vitapad). With use of this therapy trauma patients suffering infectious complications can be treated very effective, which can reduce the overall time needed for treatment and can result in diminished invalidity.

Successful treatment of infected vascular prosthetic grafts in the groin using conservative therapy with povidone-iodine solution.

Four cases of infected vascular prosthetic graft in the groin successfully treated with povidone-iodine solution using a conservative approach are described here. In all patients the same technique was used. After complete debridement, the prosthetic graft in the groin was completely exposed. The wound was cleansed with hydrogen peroxide and then dressed with gauze soaked in 1:10 sterile water-diluted povidone-iodine solution. The dressings were changed twice a day. The patients were supplemented by systemic therapy of an appropriate antibiotic. All patients were observed in the intensive care unit. In all patients this treatment method led to control of infection and healing of the wound. Thus, it was not necessary to remove the prosthetic graft and patients were spared a major surgical intervention. At follow-up, the prosthetic grafts remain patent without any signs of recurrence of infection.

Treatment of infectious diarrhea in children.

Diarrheal diseases remain an important cause of childhood morbidity and death in developing countries, although diarrheal deaths have significantly declined in recent years, mostly due to successes in the implementation of oral rehydration therapy (ORT), which is the principal treatment modality. Diarrhea may occur for varied reasons; however, most episodes of diarrhea in developing countries are infectious in origin. Three clinical forms of diarrhea (acute watery diarrhea, invasive diarrhea, and persistent diarrhea) have been identified to formulate a management plan. Acute diarrhea may be watery (where features of dehydration are prominent) or dysenteric (where stools contain blood and mucus). Rehydration therapy is the key to management of acute watery diarrhea, whereas antimicrobial agents play a vital role in the management of acute invasive diarrhea, particularly shigellosis and amebiasis. In persistent diarrhea, nutritional therapy, including dietary manipulations, is a very important aspect in its management, in addition to rehydration therapy. Rehydration may be carried out either by the oral or intravenous route, depending upon the degree of dehydration. Oral rehydration salts (ORS) solution (World Health Organization formula) is recommended for ORT. Intravenous fluid is recommended for initial management of severe dehydration due to diarrhea, followed by ORT with ORS solution for correction of ongoing fluid losses. Antimicrobial therapy is beneficial for cholera and shigellosis. Antiparasitic agents are indicated only if amebiasis and giardiasis are present. Appropriate feeding during diarrhea is recommended for nutritional recovery and to prevent bodyweight loss. Antidiarrheal agents do not provide additional benefit in the management of infectious diarrhea. Although some probiotics have been shown to be beneficial in the treatment of acute diarrhea due to rotavirus, their use in the treatment of diarrhea is yet to be recommended, even in developed countries. The children of developing countries might benefit from zinc supplementation during the diarrheal illness, but its mode of delivery and cost effectiveness are yet to be decided.

Comparison of antibiotic administration in conjunction with supportive measures versus supportive measures alone for treatment of dairy cows with clinical mastitis.

OBJECTIVE: To determine whether antibiotic and supportive treatment would improve outcome for dairy cows with naturally developing clinical mastitis, compared with supportive treatment alone. DESIGN: Randomized controlled trial. ANIMALS: 124 cows in one herd with 172 episodes of clinical mastitis. PROCEDURE: Cows were examined at the onset of clinical mastitis, assigned a severity score, and randomly assigned to receive antibiotic (intramammary administration of cephapirin, i.v. administration of oxytetracycline, or both) and supportive treatment (administration of oxytocin, stripping of affected glands, and, in severely affected cows, administration of flunixin meglumine or fluids) or supportive treatment alone. Treatment was continued until 24 hours after signs of clinical mastitis resolved (clinical cure). Milk samples from affected glands were submitted for bacterial culture before initial treatment and every 2 weeks thereafter until the causative organism was no longer isolated (bacteriologic cure). RESULTS: When mastitis was caused by Streptococcus spp or coliform bacteria, clinical cure rate by the tenth milking was significantly higher if antibiotics were used. Bacteriologic cure rate at 14 days was significantly higher when antibiotics were used, particularly if mastitis was caused by Streptococcus spp. Cows receiving antibiotics developed fewer subsequent episodes of clinical mastitis during the 60 days after the initial episode of mastitis and had less severe clinical disease than cows that did not. CLINICAL IMPLICATIONS: Results suggest that, in herds in which mastitis is often caused by environmental bacteria, antibiotic and supportive treatment may result in a better outcome for cows with clinical mastitis than supportive treatment alone.

[Analysis of cases with liver abscess following transcatheter arterial chemoembolization (TAE) for malignant hepatic tumors].

A total of 182 TAE procedures were carried out in 98 patients with malignant hepatic tumors during the last five years. Liver abscess following TAE occurred in 3 cases (3.1%) and in 3 procedures (1.7%). All cases were discharged after successful percutaneous transhepatic abscess drainage. One case had hepatocellular carcinoma. Another case had undergone total gastrectomy and esophagojejunostomy with Roux-Y reconstruction for gastric leiomyosarcoma. The other had undergone right hemicolectomy and pancreatoduodenectomy for colon cancers and carcinoma of the ampulla of Vater. Communication between the abscess and the intrahepatic bile duct was recognized in 2 cases. In the abscess culture, E. coli and Citrobacter freundii were detected. These results suggest the major factor leading to abscess formation is biliary infection. Therefore, a previous bilio-enteric anastomosis should be regarded as a risk factor for liver abscess following TAE.

Serratia marcescens infected silk suture rejected by combined acupuncture, moxibustion and low-power laser therapy from the abdominal fascia.

Upper abdominal pains lasting 12 years after cholecystectomy, were improved in an 82-year-old woman following the rejection of indigestable silk surgical sutures induced by combined therapy of acupuncture, moxibustion and low-power laser beam irradiation directed to an old post-cholecystectomy scar. An inflammatory reaction followed by granulation tissue mass was developed. Embedded in the granulation tissue were the above mentioned silk sutures which finally were expelled through the skin at the operation scar. A surgical procedure suggested to the patient, in case of acupuncture therapy failure, was obviously avoided. Serratia-marcescens infection of the expelled material was bacteriologically defined.

[Effect of hyperbaric oxygenation on delayed hypersensitivity and antibody formation in patients with peritonitis]. / Vliianie giperbaricheskoi oksigenatsii na giperchuvstvitel'nost zamedlennogo tipa i antiteloobrazovanie u bol'nykh peritonitom.

The inhibition of the formation of hypersensitivity of delayed type to staphylococcus, Proteus, blue pus bacillus and Escherichia coli was found in patients with peritonitis given complex treatment including hyperbaric oxygenation, against the background of stimulation of the antibody formation to these bacteria. The level of staphylococcal alfa-antitoxin in the blood serum remained substantially lower than that of healthy people whether the treatment included HBO or not. The data obtained show the expediency of early use of HBO in patients with peritonitis.

[Animal experiment studies of the synergism between acylureido- penicillins and immunoglobulin G]. / Tierexperimentelle Untersuchungen zum Synergismus zwischen Acylureido-Penicillinen und Immunoglobulin G.

Animal experiments revealed that the simultaneous administration of mezlocillin and immunoglobulin G (IgG) caused a highly significant increase in the elimination of beta-lactamase producing strains of the species E.coli or Proteus spp. as compared to a mezlocillin-monotherapy. This synergistic effect is due to an inhibition of the enzymic activity of the beta-lactamases by antibodies as could be demonstrated by using enzyme crude extracts. In vivo studies on the stimulation of phagocytosis revealed that only an intact 7S IgG-preparation obtained by reduction and alkylation stimulated phagocytosis, whereas cleaved or acid-treated products were ineffective.