Staphylococcal Septicemia Research Articles

Phase 1b Dose Escalation Study of Erlotinib in Combination with Infusional 5-Fluorouracil, Leucovorin, and Oxaliplatin in Patients with Advanced Solid Tumors

Erlotinib (Tarceva) is a potent epidermal growth factor receptor (HER1) inhibitor. Infusional 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (FOLFOX) is a standard therapy for colorectal cancer. This trial assessed the maximum tolerated dose (MTD), safety, preliminary efficacy, and pharmacokinetics of erlotinib combined with FOLFOX. Patients with advanced solid tumors were sequentially enrolled into three cohorts (cohort 1: 100 mg/d erlotinib, 65 mg/m(2) oxaliplatin, 200 mg/m(2) leucovorin, 400 mg/m(2) bolus 5-FU, and 400 mg/m(2) continuous infusion 5-FU; cohort 2: oxaliplatin increased to 85 mg/m(2) and 5-FU infusion increased to 600 mg/m(2); and cohort 3: erlotinib increased to 150 mg/d). Thirty-two patients were enrolled (23 with colorectal cancer): no dose-limiting toxicities (DLT) were observed in cohort 1. In cohort 2, two of nine patients experienced a DLT (both diarrhea). In cohort 3, two of nine patients had a DLT (diarrhea and staphylococcal septicemia). Cohort 3 determined the MTD cohort and expanded to 17 patients in total. The most common adverse events were diarrhea, nausea, stomatitis, and rash (primarily mild/moderate). No pharmacokinetics interactions were observed. One patient (colorectal cancer) had a complete response, seven patients had a partial response, and nine had stable disease. The MTD was defined as follows: 150 mg/d erlotinib, 85 mg/m(2) oxaliplatin; 200 mg/m(2) leucovorin, 400 mg/m(2) bolus 5-FU, and 600 mg/m(2) infusion 5-FU. At the MTD, the combination was well tolerated and showed antitumor activity, warranting further investigation in patients with advanced colorectal cancer and other solid tumors.

Staphylococcal Infections

Staphylococcal Infections

Staphylococcal Infections

Staphylococcal Infections

Splenic Abscess Associated with Endocarditis in a Patient on Hemodialysis: A Case Report

Splenic abscess is an unusual condition usually seen in immunocompromised patients or associated with intravenous drug abuses. Several conditions including trauma, immunodeficiency, corticosteroid and/or immunosuppressive therapy and diabetes mellitus have been listed under the predisposing factors for a splenic abscess. Splenic abscess in a patient on hemodialysis is a rare but life-threatening condition if not corrected. We describe a case of splenic abscess with bacterial endocarditis on maintenance hemodialysis. He had staphylococcal septicemia secondary to bacterial endocarditis at the mitral valve from the dialysis accesssite infection. Although hematologic seeding from endocarditis has been the predisposing factor for splenic abscess, we postulate that access-site infections may predispose hemodialysis patients to splenic abscess. Splenic abscess may be considered as one of the causes when patients on hemodialysis develop unexplained fever.

Successful Use of ECMO in Adults with Life-threatening Infections

Two cases of critically ill patients who received extracorporeal membrane oxygenation (ECMO) using different forms of circuitry and for different indications are presented. Both patients had life-threatening infections with septic shock and were not able to be supported by conventional means. The first patient had staphylococcal septicaemia and received venoarterial ECMO for circulatory failure. The second patient had psittacosis and received venovenous ECMO for respiratory failure. We discuss the expanding indications for this technology and the role it has to play in adult intensive care.

Primary Aorto-duodenal Fistula Following Staphylococcal Septicaemia

A 73-year-old lady presented to the emergency department with a 6 h history of haematemesis, abdominal pain and back pain. On examination she was haemodynamically stable and abdominal examination revealed a non-tender abdominal aortic aneurysm (AAA). Haemoglobin was 7 g/dl. Eleven weeks previously she had undergone a coronary angiogram, followed 2 days later by an angioplasty and stent insertion. Because of a suspected coronary artery dissection the femoral sheath was left in situ for 24 h as a precaution. She was discharged well 3 days later. She returned 1 day after discharge with a staphylococcal septicaemia, which resolved with antibiotic treatment. During this admission she had several episodes of melaena. Upper GI endoscopy demonstrated a gastric ulcer and abdominal ultrasound revealed a 3.4 cm abdominal aortic aneurysm. Emergency contrast CT scan demonstrated an aorto-duodenal fistula with peri-aortic inflammation (Fig. 1). At endoscopy no abnormality was found in the stomach or duodenum. At laparotomy a 4 cm AAA, adherent to the third part of the duodenum was found. The distal small bowel was full of blood. The proximal aorta and iliac vessels were normal. Following infra-renal aortic cross clamping the duodenum was dissected off the aorta. A 1 £ 1 cm defect in the aorta plugged by thrombus and connected to the third part of the duodenum was found. The aorta was repaired with an in situ bifurcated rifampicin-soaked graft, the duodenal defect was closed with 3/0 polyglyconate and an omental flap was interposed between repairs. A specimen of aortic tissue and an aortic swab were cultured and grew Staphylococcus aureus sensitive to flucloxacillin. The patient was treated with the appropriate intravenous antibiotics postoperatively. A peri-graft collection developed in the second post-operative week (Fig. 2). Aspirate from this collection grew Pseudomonas. This resolved on double anti-pseudomonal therapy. The patient remained in hospital for 9 weeks for intravenous antibiotic therapy. Serial CT scans and measurement of inflammatory markers confirmed resolution of infection and she was discharged well. Follow-up CT scan at 5 months demonstrated complete radiographic resolution (Fig. 3).

P263 Staphylococcal septicaemia in an intravenous drug user

P263 Staphylococcal septicaemia in an intravenous drug user

Cardiopulmonary resuscitation following minimally invasive repair of pectus excavatum (Nuss technique)

Pectus excavatum is a common chest wall deformity, occurring in approximately one in every 1000 children [1]. The congenital deformity is characterized by a concave, funnel-shaped chest, which is usually mild at birth, but becoming more severe with growth, particularly during teenage years. Although the most common indication for repair is cosmetic, the majority of patients with severe deformity will suffer from shortness of breath, tachycardia, palpitations and chest discomfort [2]. Cardiac compression/displacement and atelectasis have been demonstrated on CT scanning [3]. Association between thoracic skeletal abnormalities and mitral valve prolapse syndrome (MVPS) is reported [4]. Other reports have highlighted the association between MVPS, cardiac arrhythmias [5] and sudden death [6]. Traditional correction of pectus excavatum is a long procedure, involving resection of bone and cartilage. More recently, a technique of minimally invasive repair has been developed by Donald Nuss [3]. A strong convex steel bar (Fig. 1) spanning the width of the anterior chest wall (Fig. 2) is inserted laterally and fed under the sternum through small bilateral incisions. The bar is inserted at a level corresponding with the maximal sternal depression, usually the 6 /8th intercostals space and secured at its lateral ends by suturing to chest wall muscle. The bar is removed after 2 years when permanent chest wall remodelling has occurred. Excellent long-term results have been achieved with a low complication rate [2,3,7]. Serious complications including cardiac perforation, bilateral empyema, bacterial pericarditis, staphylococcal septicaemia and thoracic outlet syndrome have, however, been reported [8]. We would like to raise some issues concerning cardiopulmonary resuscitation (CPR) in this group of patients. The likelihood of these patients requiring CPR, although small, may be greater than in the general population as a consequence of a primary dysrrhythmia or complication of surgery. Correct placement of defibrillation paddles is important to optimize the chances of successful defibrillation and minimize defibrillation energy requirements. The current International Liaison Committee on Resuscitation (ILCOR) guidelines recommend either an anterior-lateral (one electrode just to the right of the upper sternal border below the clavicle; the other to the left of the nipple with the center of the electrode in the mid-axillary line) or anterior /posterior (one paddle over the left precordium; the other in a right infrascapular position) positioning of the defibrillation paddles [9]. Clinically, the anteriorlateral position provides easier access for defibrillation paddles and is the more commonly used position at cardiac arrests. This anterior-lateral position may not be appropriate in patients who have undergone this procedure. The ends of the metal Nuss bar would be positioned close to anterior-laterally placed defibrillator paddles, longitudinal to any current flow, and are likely to present a path of low resistance along which current will flow preferentially. This will result in diversion of current away from the myocardium and decrease the chance of successful defibrillation. Although the current pathway traverses the Nuss bar when paddles are placed in the anterior /posterior position, a posteriorly placed pad will force current to traverse the chest, although actual current distribution is likely to be affected by the Nuss bar. Because the bar is transverse to the direction of current flow, is likely to have much less adverse effect on current pathways. We concur with the manufacturer’s recommendations that defibrillation should be carried out with the defibrillation paddles placed in an anterior /posterior position. Posterior paddle placement, as described for defibrillation in the prone position [10], may also be suitable. * Tel.: /44-2380-796720; fax: /44-2380-794348. E-mail address: ppicton@surfree.co.uk (P. Picton). Resuscitation 57 (2003) 309 /310

The mouth as a source of coagulase negative staphylococcal septicaemia in low birth weight neonates

The mouth as a source of coagulase negative staphylococcal septicaemia in low birth weight neonates

Curtailing unnecessary vancomycin usage in a hospital with high rates of methicillin resistant Staphylococcus aureus infections.

To implement and monitor the effectiveness of a strategy to curb unnecessary use of vancomycin and teicoplanin for inpatients in a teaching hospital/tertiary referral centre where 33% of S. aureus isolates (72% from ICU patients) were methicillin resistant. A sample of 182 vancomycin/teicoplanin inpatient prescriptions surveyed, revealed that only 31 (17%) conformed with Centre for Disease Control (CDC) guidelines. Following education (ward-rounds, bulletins) on appropriate CDC based guidelines for prescribing glycopeptides directed at relevant clinicians, 'Immediate Concurrent Feedback' (ICF) was gradually deployed throughout the hospital. This entailed review of respective inpatient records on the next working day. If the indication was deemed not to conform with our guidelines, the prescriber was issued a memo (copied to the supervising doctor). Each memo detailed the 'errant' incident, listed appropriate indications and explicitly advised desisting from such prescribing and suggested alternative therapy if necessary. Corresponding glycopeptide usage data for our hospital and others in Hong Kong were retrieved and analysed as were samples of records of our inpatients with staphylococcal septicaemia (pre and during ICF). Compared with baseline values, during 2 years of ICF, inpatient prescribing of vancomycin and teicoplanin deemed to conform increased to 71% (773/1086); difference 54% (P < 0.0001, 95% CIs 47-62%). Corresponding average monthly usage (DDDs/1000 admissions) decreased from 76 (pre-ICF) to 45; mean difference 31 (P < 0.0001, 95% CIs 24, 38). Mortality from staphylococcal bacteraemia remained unchanged. No comparable changes in glycopeptide usage ensued in comparator hospitals. ICF can be used safely to curb irrational overuse of vancomycin and teicoplanin in a hospital with high methicillin resistant S. aureus infection rates.

Prevalence of molecular types and mecA gene carriage of coagulase-negative Staphylococci in a neonatal intensive care unit: relation to nosocomial septicemia.

Molecular typing of isolates revealed that neonatal coagulase-negative staphylococcal (CONS) septicemia is most frequently caused by predominant, antibiotic-resistant CONS types, which are widely distributed among both neonates and staff of the neonatal unit, suggesting cross-contamination. Therefore, infection control measures may be valuable in the prevention of this common nosocomial septicemia.

Potential role of human brain microvascular endothelial cells in the pathogenesis of brain abscess: inhibition of Staphylococcus aureus by activation of indoleamine 2,3-dioxygenase.

Cerebral abscess is a rare complication of staphylococcal septicemia in infants associated with high mortality and morbidity. In the pathogenesis of abscess formation, S. aureus, one major causative agent, interacts with endothelial cells of the brain vessels before reaching the central nervous system. This study examined the growth of S. aureus in human brain microvascular endothelial cells (HBMEC) cultures stimulated with cytokines. IFN-gamma inhibited S. aureus replication by the induction of indoleamine 2,3-dioxygenase (IDO) in HBMEC. This activation of IDO in HBMEC could be shown by RT-PCR and by detection of kynurenine in culture supernatants of activated cells. Resupplementation of L-tryptophan abrogated the inhibitory effect of IFN-gamma on the growth of staphylococci, hence confirming the activation of indoleamine 2,3-dioxygenase as being responsible for the induced bacteriostasis. Addition of TNF-alpha enhanced the IFN-gamma mediated antibacterial effects, whereas TNF-alpha alone had no influence on staphylococcal growth. Stimulation of HBMEC with IFN-gamma failed to activate inducible nitric oxide synthase (iNOS) and subsequent production of nitric oxide (NO). Thus, intra- and extracellular depletion of L-tryptophan seems to be an important process in the defense against staphylococcal brain abscesses by means of creating an unfavorable microenvironment.

Myocardial abscess with contained rupture: successful repair

Spontaneous rupture of the heart from myocardial abscess is a rare occurrence. Most cases of spontaneous cardiac rupture are due to myocardial infarction. We present a case of a contained rupture of the heart in a patient with staphylococcal septicemia. Although cultures from the pericardial space were negative the macroscopic and clinical picture was compatible with an abscess.

Acute thrombocytopenic crisis following burns complicated by staphylococcal septicaemia

The pathophysiological changes in a burn patient can at times manifest as severe complications, the management of which can be extremely challenging to the burn surgeon. A case report of an adult male with burns (18% total body surface area) who developed an acute unexpected thrombocytopenia crisis (2×10 9 l −1) on day 3 followed by disseminated intravascular coagulation is presented. The various etiological factors and possible mechanisms leading to thrombocytopenia in burns are discussed. Minor burns may present acute major complications in the presence of other thrombocytopenic factors like trauma and sepsis and thrombocytopenia by it self can be a good indicator of sub-clinical infection.

The Epidemiology of Hospitalization of Elderly Americans for Septicemia or Bacteremia in 1991–1998: Application of Medicare Claims Data

PURPOSE: To describe the epidemiology of hospitalization of elderly Americans for septicemia or bacteremia. METHODS: Medicare claims data for discharges from 1991 through 1998 were used to study 75,920 hospitalizations with the principal diagnosis of septicemia or bacteremia in patients aged 65 years or older. RESULTS: “Unspecified septicemia” was the commonest principal diagnosis, followed by septicemia due to Escherichia coli or staphylococci. From 1991 through 1997, annual discharges for “unspecified septicemia” increased 108%, and those for pneumococcal septicemia increased 310%. Decreases in reported septicemia were seen after increases in the proportion of beneficiaries in Medicare health maintenance organizations. Discharge rates for septicemia principal diagnoses increased steeply with age. Age-specific discharge rates were usually highest for black men and lowest for white women. Exceptions included septicemia due to E. coli, with white men at low risk, and pneumococcal septicemia, without significant differences between races or sexes. The case-fatality rate in hospital ranged from 4.2% with “bacteremia” and 6.9% with E. coli septicemia to 22.2% with “septicemia due to gram-negative organism, unspecified,” and 26.8% with “unspecified septicemia.” Staphylococcal septicemia, septicemia due to pseudomonas, and septicemia due to anaerobes were the costliest common principal diagnoses in terms of the mean duration of hospital stay. CONCLUSIONS: Unexplained sharp increases were reported in hospitalization for septicemia or bacteremia in elderly Americans. Marked variation by race and sex were evident in discharge rates with these principal diagnoses. Prognosis and average cost of treatment also differed substantially among common rubrics. Further investigation of individual diagnoses should concentrate on explaining secular trends, exploring the basis for variation by race and sex, and elucidating risk factors for poor clinical outcomes.

Acute pericarditis in childhood: a 10-year experience.

Twenty children, aged 6 months to 13 years, with acute pericarditis admitted between 1987 and 1997 to a university hospital were analyzed retrospectively for their etiology, presentation, management, and prognosis. The most common types of pericarditis were purulent (40%), collagen vascular disease (30%), viral (20%), and neoplastic disease (10%). Most children presented with chest pain, fever, and tachypnea, but cardiac tamponade was not seen in any children. Staphylococcus aureus was the most frequent causative organism of purulent pericarditis and septic arthritis was the most common concurrent infection in the patients. Surgical drainage was performed for 11 cases, 9 underwent subxiphoid pericardial window, and 2 underwent thoracotomy. There was no constrictive pericarditis or reaccumulation of fluid after surgery. Two children died, one of staphylococcal septicemia and the other had a malignant mediastinal tumor. The remaining 18 made a complete recovery. We conclude that subxiphoid pericardial drainage is a simple, safe, and quick procedure and can be done easily in general hospitals by pediatric surgeons. The expensive facilities of cardiac surgeries are not needed.

Staphylococcal septicaemia in burns

This study analyses staphylococcal septicaemia in a series of 1516 burn patients who were admitted to the burn unit of the Al-Babtain Centre for Burns and Plastic Surgery, Ibn Sina Hospital, Kuwait over a period of 6.5 years (1 June 1992–31 December 1998). One hundred and nine patients (7.2%) developed clinically and microbiologically proven septicaemia, of which 80 (73.4%) showed one or the other type of Staphylococcus in their blood. Fifty (62.5%) of them were males and 30 (37.5%) females, with a mean age of 26 years and the mean total body surface area of burns (TBSA) of 45% (range 1–93%). Preschool age children comprised 27.5% of the patients. Flame was the dominant (80%) cause of burn. Of the 80 patients who had 91 episodes of septicaemia, 52 (65%) had MRSA, 8 (10%) MSSA, 11 (13.8%) MRSE and 5 (6.2%) MSSE and 4 (5%) others had mixed organisms. Only the patients with MRSA had multiple episodes. Eight patients (10%) showed septicaemic episodes within only 48 h of admission; however, the majority of the patients (77.5%) had a septicaemic attack within 2 weeks postburn. Of the 52 MRSA septicaemic cases, 39 (75%) survived and 13 (25%) died. Four patients with septicaemia due to mixed infections died. A total of 19 patients were intubated, 14 due to inhalation injury and 5 because of septicaemia; all in the former group died. Glycopeptide therapy (vancomycin/teicoplanin) was instituted immediately following the detection of staphylococci in the blood. No significant difference was noted in relation to mortality amongst the septicaemic patients, whether or not on prophylactic antibiotic. Fifty-six (70%) of the 80 patients had 139 sessions of skin grafting and survived. Of the 52 MRSA patients, 40 had 101 sessions of skin grafting and 33 of them survived. The apparent low mortality was probably due to early detection of the organism, appropriate antibiotic therapy, care for nutrition and early wound cover. This study indicates a high incidence of staphylococcal septicaemia (especially due to MRSA) in the burn unit. A surface wound is the likely source of entry to the blood stream in these immunocompromised patients. The organism could be detected in blood as early as 48 h postburn and in as little TBSA burn as 1% in this MRSA endemic unit. Inhalation injury with major burns and added staphylococcal septicaemia invariably proved to be fatal.

Infective Endocarditis—An Uncommon Cause of Unexpected Death

ABSTRACTInfective endocarditis can rarely present as a sudden or unexpected death occurring outside of hospital. Two such cases were studied and the diagnosis was determined only after autopsy examination. A 36-year-old male intravenous drug abuser had staphylococcal and enterococcal septicemia and endocarditis of the mitral valve. He died in jail five days after presenting with nausea and vomiting. The other case was an asymptomatic 30-year-old male with a bicuspid aortic valve and a coarctation of the aorta who developed Streptococcus viridans endocarditis and was found dead at home one hour after last being seen alive. Both had left ventricular failure from valve perforation and subsequent valve incompetence. The drug abuser had evidence of disseminated infection. Infective endocarditis was confirmed by appropriate histopathological examination and microbiological culture.

Epidural abscess in an infant

We report the case of a 2-year-old infant who developed a staphylococcal septicaemia that subsequently resulted in an epidural abscess and paraparesis. The significance of early diagnosis and the roles of anterior surgery to decompress the spinal cord, debride infection and correct deformity are discussed.

Community-acquired severe staphylococcal septicemia in children: the relationship with blunt trauma.

With the aim of establishing the role of blunt trauma, a trauma without any fracture or obvious wound, as a risk factor in children who were admitted for community-acquired severe staphylococcal septicemia with various organ involvement, 63 patients were investigated during a seven-year study period. All children were previously healthy. Blunt trauma was present in 12 (46%) of 26 septicemic patients in whom skeletal infections were diagnosed and the relative risk of trauma was high (odds ratio 15.0; confidence interval 2.9-75.8, P < 0.001) in these children. Patients with multiple organ involvement and with multifocal skeletal infections were more frequent among traumatized patients. Children with skeletal involvement were significantly older than others (P < 0.001). The period between the first symptom of infection and the diagnosis was shorter in traumatized children (P < 0.001). None of the children with staphylococcal pulmonary or soft tissue infection had any history of trauma. We conclude that blunt trauma is one of the important risk factors for skeletal involvement in staphylococcal septicemia. Its immunosuppressive nature, especially in local damage of the skin barrier, may be the cause of seeding and multifocal infection.