Broad-spectrum Antimicrobial Therapy Research Articles

TDM-Guided Therapy with Daptomycin and Meropenem in a Morbidly Obese, Critically Ill Patient

To describe a case of severe cellulitis, successfully treated with high-dose daptomycin plus continuous infusion meropenem, in a patient with morbid obesity and renal failure, in whom drug exposure over time was optimized by means of real-time therapeutic drug monitoring (TDM). A 63-year-old man with morbid obesity (body mass index 81.6 kg/m²) and renal failure was admitted to the emergency department because of severe cellulitis. The patient had an admission Laboratory Risk Indicator for Necrotizing Fasciitis score of 9, and broad-spectrum antimicrobial therapy with daptomycin and meropenem was started. Because of rapidly changing renal function, dosage adjustments were guided by an intensive program of TDM (daptomycin ranging from 1200 mg every 48 hours over 30 minutes to 1200 mg every 36 hours over 30 minutes; meropenem ranging from 0.25 g every 8 hours over 6 hours to 500 mg every 4 hours by continuous infusion). Clinical response was observed within 72 hours. However, a sudden increase of serum creatine kinase (SCK) raised questions about the need for discontinuation of daptomycin. The drug concentrations were not toxic; therefore, we decided to continue therapy. Significant clinical improvement, with SCK normalization, was observed within a few days. Antimicrobial therapy was switched on day 29 to amoxicillin/clavulanate plus levofloxacin, and then discontinued at discharge on day 53. High-dose daptomycin plus continuous infusion meropenem may ensure adequate empiric antimicrobial coverage in patients with possible early necrotizing fasciitis. However, in patients with morbid obesity and changing renal function, significant challenges may arise because of the hydrophilic nature of these drugs and the inaccuracy of standard methods of estimating renal function. Real-time TDM may represent an invaluable approach in optimizing drug exposure with high-dose daptomycin plus continuous infusion meropenem in patients with severe cellulitis, morbid obesity, and changing renal function.

Clustering of polyclonal VanB‐type vancomycin‐resistant Enterococcus faecium in a low‐endemic area was associated with CC17‐genogroup strains harbouring transferable vanB2‐Tn5382 and pRUM‐like repA containing plasmids with axe‐txe plasmid addiction systems

VanB-type vancomycin-resistant Enterococcus faecium isolates (n = 17) from 15 patients at the Örebro University hospital in Sweden during a span of 18 months was characterized. All patients had underlying disorders and received broad-spectrum antimicrobial therapy. Pulsed-field gel electrophoresis (PFGE) grouped 14 isolates in three PFGE types and three isolates in unique PFGE patterns. All isolates had multi-locus sequence types [ST17 (n = 5); ST18 (n = 3); ST125 (n = 7); ST262 (n = 1); ST460 (n = 1)] belonging to the successful hospital-adapted clonal complex 17 (CC17), harboured CC17-associated virulence genes, were vanB2-positive and expressed diverse vancomycin minimum inhibitory concentration (MICs; 8 to > 256 mg/L). Isolate 1 had a unique PFGE type and a chromosomal transferable vanB2-Tn5382 element. Interestingly, the other five PFGE types had Tn5382 located on plasmids containing pRUM-like repA and a plasmid addiction system (axe-txe) shown by co-hybridization analysis of PFGE-separated S1-nuclease digested total DNA. The resistance plasmids were mainly of 120-kb and supported intraspecies vanB transfer. Two strains were isolated from patient 6 and we observed a possible transfer of the vanB2-resistance genes from PFGE type III ST460 to a more successful PFGE type I ST125. This latter PFGE type I ST125 became the predominant type afterwards. Our observations support the notion that vanB-type vancomycin-resistant Enterococcus faecium can persist in a low-endemic area through successful clones and plasmids with stability functions in hospital patients with known risk factors.

Linezolid Therapy of Brain Abscess

To the Editors: Brain abscess is a serious and uncommon intracerebral infection with limited therapeutic options in children.1,2 When no positive cultures are obtained, empiric treatment should be initiated with a broad-spectrum antimicrobial therapy.1,2 We studied the medical records of 7 children (4 males and 3 females) who had been diagnosed with brain abscess at the Bambino Gesù Children Hospital, Rome from 2004 to 2009. Microbiologic findings were positive in only 2 cases (Streptococcus constellatus in one patient and Streptococcus intermedia in another). On admission all patients promptly received intravenous antibiotic therapy. In all but 1 patient, there was no improvement. For this reason, the initial therapy was discontinued after an average of 11 days. We administered linezolid, either alone or associated with other antimicrobial agents. In one case, we decided to stop first line therapy and to start linezolid because of the availability of oral formulation. The dosage of linezolid was 30 mg/kg/daily given intravenously for median of 6 weeks (range, 27–70 days). The other patient received oral linezolid in a dosage of 1200 mg/daily. Linezolid therapy was associated with a progressive improvement in both the clinical condition and radiologic imaging. Conservative medical treatment of the abscess was sufficient for 3 patients. In Table, Supplemental Digital Content 1, https://links.lww.com/INF/A571, therapy schedule is summarized for each patient. Some patients were discharged with oral antibiotic therapy after a main period of 50 days hospitalization. After an average period of 18 months (range, 6–51 months), all patients were in good clinical condition, except 1 who experienced seizures at home. We chose linezolid therapy because of its favorable pharmacodynamic properties, such as the possibility of both intravenous and oral administration.3–5 This is particularly important for prolonged antibiotic treatment, to reduce the number of complications due to venous catheterization and the period of hospitalization. We had just 1 case of neutropenia, which disappeared 1 week after therapy discontinuation. Andrzej Krzysztofiak, MD Elena Bozzola, MD Laura Lancella, MD Anna Quondamcarlo, MD Francesco Gesualdo, MD Alberto G. Ugazio, MD Infectious Disease Unit Pediatric Department Bambino Gesù Children Hospital Rome, Italy

Strongyloides Stercoralis Infection after Autologous Hematopoietic Stem Cell Tranplantation

Purpose: Introduction: Strongyloides stercoralis affects anywhere from 30 to 100 million people in 70 countries and is a common cause of diarrhea. Strongyloidiasis is usually a chronic and limited disease; however in immunocompromised patients hyperinfection syndrome (HIS) can occur. Diagnosing strongyloidiasis early is important as almost all deaths due to helminths in the United States are because of S. stercoralis (SS) HIS. We present a case of SS diagnosed on upper endoscopic biopsy of the duodenum. Case: A 72 year-old man with multiple myeloma (MM) diagnosed in 2009 was treated with high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). During ensuing neutropenic period patient developed fever and diarrhea. Patient was started on broad spectrum antimicrobial therapy. Blood and urine cultures and stool studies were negative for infection. With persistent diarrhea, an upper and lower endoscopy was performed day +16 after HSCT. Findings included mild duodenitis and biopsies revealed numerous SS organisms deep in the crypts of the duodenal mucosa. Patient was started on Ivermectin with initial resolution of fever and diarrhea. On day +28 after HSCT, patient had mental status changes. Magnetic resonance imaging of brain showed encephalitis. Lumbar puncture revealed 903 white blood cells/ml but no organisms. Albendazole was added to Ivermection with presumed SS-HIS. With progressive multi-organ dysfunction, patient expired on day +38 after HSCT. Discussion: S. stercoralis is able to replicate in the human host allowing auto-infection and continuation of parasitism. The case fatality rate of HIS in patients with diminished cellular immunity is 86%. There are 5 known cases in the English literature of HSCT recipients in whom SS-HIS or dissemination was diagnosed after transplantation, 4 of which resulted in death. Single stool inspection is unable to detect SS larvae in 70% of cases. Endoscopy can establish the diagnosis of SS. Conclusion: We recommend early endoscopy and maintaining a low threshold to biopsy an unimpressive appearing bowel in immunocompromised patients. Especially in HSCT recipients, prompt diagnosis and treatment is imperative to prevent mortality.

Case 25-2010

A 24-year-old woman was transferred from another hospital because of abdominal pain and shock. Computed tomographic scans of the abdomen showed ascites, thickening of a segment of small bowel, and mesenteric lymphadenopathy. Laparotomy revealed two areas of necrotic small bowel, which were resected. Despite broad-spectrum antimicrobial therapy, she remained critically ill. On the seventh hospital day, a diagnostic test result was received.

Aspergillose cutanée secondairement invasive chez un nouveau-né prématurissime : cas clinique et revue de la littérature

Aspergillus is a ubiquitous fungus that can cause primary cutaneous aspergillosis in extremely low-birth-weight (ELBW) neonates, then be invasive and lead to death. ELBW neonates are particularly at risk because of decreased qualitative immune defenses and defects in the skin barrier. Broad-spectrum antimicrobial therapy and corticosteroids, often used in these patients, contribute to increased risk. We present a fatal case of primary cutaneous aspergillosis complicated with invasive aspergillosis, confirmed by autopsy, in an ELBW infant. The source of contamination was probably non-sterile disposable latex gloves used for neonatal care. The early recognition of this source led to its eviction for other hospitalized ELBW infants and no outbreak was observed.

Management of febrile neutropenia: ESMO Clinical Practice Guidelines

Management of febrile neutropenia: ESMO Clinical Practice Guidelines J. de Naurois, I. Novitzky-Basso, M. J. Gill, F. Marti Marti, M. H. Cullen & F. Roila On behalf of the ESMO Guidelines Working Group* Department of Medical Oncology; Department of Haematology; Department of Clinical Microbiology, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK; Department of Medical Oncology, S. Maria Hospital, Terni, Italy

Management of an unfortunate triad after breast reconstruction: Pyoderma gangrenosum, full-thickness chest wall defect and Acinetobacter Baumannii Infection

If diagnosed late, post-surgical pyoderma gangrenosum (PSPG) is a rare, tricky and potentially life-threatening complication. Once diagnosed, immunosuppressive agents may provoke further complications. Well-intentioned extensive serial debridement may cause deep skin and soft-tissue defects, requiring skin grafting and possible flap surgery. The combination of necessary immunosuppressive treatment, protracted hospital stay and broad-spectrum systemic antimicrobial therapy may encourage serious acquired multidrug resistance (MDR). We report an unfortunate triad following breast reconstruction of PSPG, full-thickness chest wall defect and MDR with Acinetobacter baumannii infection. Interdisciplinary treatment using free flap surgery and negative-pressure wound therapy with instillation therapy (V.A.C.Instill(R) Wound Therapy) enabled survival and complete wound closure.

Antimicrobial Use Among Patients Receiving Palliative Care Consultation

We sought to characterize antimicrobial use among patients receiving palliative care consultation. Retrospective review of patients seen by the Palliative Care Service at the University of Michigan Health System from January 2008 to May 2008. Of 131 patients seen in consultation, 70 received antimicrobials. We identified 92 infections among these 70 patients; therapy for 54 (58.7%) was empiric. Empiric therapy was most commonly prescribed for respiratory infection and urinary tract infection. Piperacillin/tazobactam (P/T) was the most frequently used agent, with 26 patients receiving P/T (37.1%); 22 of 26 received this agent empirically (84.6%, P = .005). Vancomycin was prescribed to 23 patients (32.9%). Sixteen patients (22.9%) died in hospital; another 31 were enrolled in hospice care. Our results suggest significant use of empiric, broad-spectrum antimicrobial therapy among hospitalized patients near the end of life. We advocate for careful assessment of potential benefits and treatment burdens of antimicrobial therapy, especially when palliation is the goal.

Case 26-2009

A 34-year-old man with cystic fibrosis was admitted to this hospital because of cough, increased dyspnea, and sputum production. Broad-spectrum antimicrobial therapy was initiated. On the fifth hospital day, fever developed, and on the eighth day, nausea, vomiting, leukocytosis, and acidosis developed. The next day, a diagnostic procedure was performed.

Balamuthia mandrillaris meningoencephalitis in an immunocompromised patient

Balamuthia mandrillaris is a rare but increasingly recognized cause of amebic encephalitis, yet it remains poorly understood. The condition is almost universally fatal, and due to diagnostic difficulty, most cases are identified postmortem. The authors report a case of Balamuthia amebic encephalitis in a patient with combined variable immunodeficiency in which a rare antemortem diagnosis was made via brain biopsy. Despite broad-spectrum antimicrobial therapy, the outcome was fatal. Such presentations are challenging, and definitive diagnosis may require biopsy in consultation with a skilled neuropathologist.

Case 22-2009

A 59-year-old man was admitted to this hospital for induction chemotherapy for acute myeloid leukemia. On the seventh hospital day, neutropenia, fever, nausea, diarrhea, and abdominal pain developed. Despite the administration of broad-spectrum antimicrobial therapy, tender, erythematous skin lesions developed on the trunk, abdomen, and arms and legs, and bilateral pulmonary nodules were seen on computed tomographic scans of the chest. A diagnostic procedure was performed.

Chitinophaga terraeBacteremia in Human

<i>Chitinophaga terrae</i>Bacteremia in Human

Respiratory Disease Associated with Bordetella bronchiseptica in a Hoffmann's Two-Toed Sloth (Choloepus hoffmanni)

A 2-yr-old female captive-born Hoffmann's two-toed sloth (Choloepus hoffmanni) presented with respiratory disease. A severe inspiratory dyspnea with nasal congestion was observed with open-mouthed breathing and bilateral mucopurulent nasal exudate. Despite initial treatment with broad-spectrum antimicrobial therapy and anti-inflammatory and supportive care, the dyspnea persisted. The animal was anesthetized for bronchoscopy to obtain a deep tracheal sample. Based on culture of Bordetella bronchiseptica and sensitivity, a combination of systemic enrofloxacin, dexamethasone, and coupage with nebulization of saline, gentamicin, and albuterol as well as supportive care resulted in full recovery after 6 weeks of treatment.

ErratumBalamuthia mandrillaris meningoencephalitis in an immunocompromised patient.

Balamuthia mandrillaris is a rare but increasingly recognized cause of amebic encephalitis, yet it remains poorly understood. The condition is almost universally fatal, and due to diagnostic difficulty, most cases are identified postmortem. The authors report a case of Balamuthia amebic encephalitis in a patient with combined variable immunodeficiency in which a rare antemortem diagnosis was made via brain biopsy. Despite broad-spectrum antimicrobial therapy, the outcome was fatal. Such presentations are challenging, and definitive diagnosis may require biopsy in consultation with a skilled neuropathologist.

Health-Care-Associated Pneumonia

Health-Care-Associated Pneumonia

Letters to the Editor

16 June 2008 Dear Editor, TRIPLE INFECTION IN A CHILD Enteric fever, malaria and urinary tract infection are, individually, common infections in children of the tropical and the sub-tropical world. Co-infection with two disease-causing organisms may be more common than usually recognised because of the overlapping systemic manifestations. It is, however, unusual for an immunocompetent child to have three concomitant infections at a given time. The present communication is intended to report on a 4-year-old immunocompetent boy, with simultaneous enteric fever, Escherichia coli (E. coli) urinary tract infection and Plasmodium vivax (P. vivax) malaria. A 4-year-old, otherwise healthy, boy presented with high-grade intermittent fever associated with chills and rigor of 6-day duration. He also had increased frequency of micturition and pain in the abdomen for 3 days. The family and the past medical history were non-contributory. On physical examination, he was febrile (temperature: 103.5°F) and dehydrated. Intravenous fluids corrected the dehydration. He was a normally developing child with age-appropriate anthropometry. Mild pallor with cervical lymphadenopathy without evidence of malnutrition was noted. The abdomen was soft without concomitant tenderness. The spleen and the liver were palpable 2.5 cm and 2 cm below left and right costal margins, respectively. Suprapubic without renal angle tenderness was present. The other systems were normal. The laboratory tests showed: hemoglobin 8 g/dL; white blood cells: 4800/mm3 (52% neutrophils, 46% lymphocytes), platelets: 350 000/mm3. Serum urea and creatinine were normal. The urinary sediment analysis was significant for pus cells and leukocytes. The blood cultures and Widal test were positive (To 1:320) for Salmonella typhi. Ceftriaxone injection was started for enteric fever. The urine and stool cultures for the same organism were negative. The cultures of the urine, however, grew E. coli which was sensitive to ofloxacin. Thus, ofloxacin injection was added. The fever failed to subside by day 4 of therapy. Repeat urine culture at the end of 4 days was sterile. The child became increasingly anorectic and the organomegaly persisted. A Giemsa-stained peripheral blood smear showed trophozoites and schizonts of P. vivax, with parasitaemia quantitatively reported as 10–40 parasites per 100 fields. The antigen test (optiMAL) for P. vivax was positive while that for Plasmodium falciparum was negative. Chloroquine was administered using the naso-gastric tube. Oral primaquine was given as per the recommendation. There was dramatic improvement in the general condition of the child with subsidence of fever within the next 36 h. Ceftriaxone injection was given for 7 days followed by 5 days of oral cefixime. Five days of injection followed by another 5 days of oral ofloxacin was administered. The Enzyme-Linked ImmunoSorbent Assay (ELISA) for HIV-I and II and the tuberculin test were negative. He was discharged on the 10th day, having made a full clinical and microbiologic recovery. He was normal on evaluation at the end of 2 weeks. The co-occurrence of three infections in an immunocompetent child is a rare event in children belonging to the developed world. It may sometimes occur in children of the tropics and the sub-tropics because of the high prevalence of several common infections. Because constitutional symptoms like fever, anorexia and vomiting are common manifestations of most of the infections, they may not always be diagnosed individually. Furthermore, administration of broad-spectrum antimicrobial therapy may be effective for more than one organism responsible for the disease manifestations, thereby masking the presence of co-infection/s. The reported child was presumed to be immunocompetent because he had no history of life-threatening infections in the past and he was developing normally. The ELISA for HIV-I and II and the tuberculin test were non-reactive which further supports the immunocompetency of the child. The laboratory tests for the cellular and humoral immunity was not carried out. Studies from Malawi indicate that malarial parasitaemia is relatively common in children with non-typhoidal salmonella (NTS) bacteraemia.1, 2 The prevalence of any bacteraemia and of NTS bacteraemia was highest in children with severe malarial anaemia, compared with the prevalence in children with cerebral malaria associated with anaemia and in those with cerebral malaria alone.3 The authors recommended antibiotic therapy for NTS infection if bacteraemia was suspected in children with severe malarial anaemia.3 More than two-thirds of NTS episodes coincided with the peak malaria transmission season.2 The incidence of malarial parasitaemia was particularly high when the co-infecting organism was NTS than other infecting organisms. Younger age at presentation and concomitant malnutrition were two prominent risk factors predisposing to co-infection.2 A study in Kenyan children, found NTS bacteraemia to be more common in children with a recent history of malaria but not with current malarial infection.4 We reiterate the importance of ruling out mixed infections in children responding sub-optimally to therapy for a diagnosed infective condition, especially in children of the tropics and the sub-tropics.

Questioning the Role of A Neutropenic Diet in Hematopoietic Stem Cell Transplantation

Neutropenic diets (ND) were developed to decrease gut-derived infections and are widely used. After finding that there were no clinical trials supporting their use, we discontinued ND in HSCT in late 2006. Our ND excluded fresh fruits and vegetables as well as black pepper, sushi, deli meats, raw milk products, soft cheeses, raw honey, miso, and yeast. It was replaced by a modified general diet (Non-ND) that permits black pepper, fresh fruits and vegetables, and homemade freshly squeezed juice - but excludes raw tomatoes. The other restrictions remain. 648 consecutive hospitalized patients were studied; 314 on ND and 314 after ND discontinuation (non-ND). All infections occurring during the first hospital stay were analyzed. All patients received ciprofloxacin 500 mg twice a day, fluconazole 200 mg daily (autograft) or voriconazole 200 mg twice daily (allograft), and acyclovir/valacyclovir. The documented infections included in the analysis comprised positive blood, urine (>100,000 organisms), BAL, stool, or wound cultures, and clostridium difficile. As the table shows, there were no differences between the ND and non-ND groups with regards to age, sex, diagnosis and conditioning regimen, or the number of days to resolution of neutropenia. There were no significant differences in the number of positive cultures between the groups during the neutropenic period. However, after the resolution of neutropenia, there was a significantly higher number of non-enteric gram-positive coccal infections in the ND group compared to non-ND. There was also a trend towards a higher incidence of C difficile, and a significantly higher incidence of new positive surveillance cultures of VRE on rectal swabs in the ND group.Tabled 1Neutropenic dietNon-neutropenic dietPAge (years)57 (18-76)56 (18-78)0.89Male:Female186:128190:1240.97Allogeneic:Autologous77:23772:2420.64Diagnosis0.91 Myeloma163165 NHL5764 AML5450 Other4039Conditioning regimen0.97 High-dose Melphalan163165 BEAM4542 Busulfan-fludarabine3233 Reduced-intensity3336 Median days to neutrophil recovery12120.91 Positive cultures during neutropenia97890.49 CoNS/MSSA/MRSA + miscellaneous gram-positive32331 C difficile24220.88 E faecium (VRE)991 Non-VRE Enterococci331 Gram-negative bacilli1590.21 S viridans11101 Fungus431 Positive cultures after resolution of neutropenia4820<0.001 CoNS/MSSA/MRSA + miscellaneous gram-positive2190.028 C difficile920.069 E faecium (VRE)730.34 Gram-negative bacilli840.38 S viridans211 Fungus111 VRE surveillance culture positivity acquired during hospitalization5631<0.004 Open table in a new tab Our findings show that there is no apparent benefit associated with ND. However, more surprising is the finding that some infections were more common with ND. It could be speculated that the microbial content of the non-ND is higher and, in the setting of broad-spectrum antimicrobial prophylaxis and therapy, such a diet could contribute to reduced colonization with virulent microorganisms. These findings suggest that additional studies are needed to investigate the role of dietary restrictions. If our findings are confirmed, a major change in an established but non-evidence-based practice will be needed. An added benefit of the more liberal diet would be greater palatability - which may contribute to reduction in the use of TPN and better nutrition.

Prehospital administered intravenous antimicrobial protocol for septic shock: a prospective randomized clinical trial

Appropriate intravenous, broad-spectrum empiric antimicrobial therapy should be initiated as rapidly as possible for suspected severe infections in the presence of hypotension. Timing and delay of initial administration of effective antimicrobial therapy is an important predictor of survival [1]. It is hypothesized that appropriate prehospital-initiated intravenous, broad-spectrum empiric antimicrobial therapy will reduce the delay of administration and will reduce mortality [2].

Fever and Purpuric Lesions in a Preschool Child

A three-year-old previously healthy girl presented to an emergency department with erythematous lesions on her nose, both cheeks and left calf associated with fever and irritability. Her guardian reported that the child’s demeanour had changed from being pleasant and happy to general irritability approximately three weeks previously. Five days before presentation, she developed clear rhinorrhea and fever, but there was no cough, otalgia or headache. The child was reluctant to walk because of left leg pain. There was no history of travel or animal exposure. Her immunizations were current. On examination she was febrile (39.6°C), tachycardic (160 beats/min) and looked miserable. The chest was clear. A vibratory systolic ejection murmur was heard at the left sternal border without radiation and heart sounds were normal. There was no lymphadenopathy. The abdomen was soft and nontender with no organomegaly. A large, warm, tender, macular erythematous lesion was seen on the right face (Figure 1) with a central purplish bulla. The lesion on the tip of the nose consisted of a purplish-blue ulcer surrounded by erythema. A similar lesion was seen on the calf. The lesions were not indurated. The neck was supple. Figure 1) Lesions on the right side of the face and nose in a three-year-old girl with irritability, fever and pancytopenia. A pen marking placed by the care team outlines the border of the erythema anteriorly The white blood cell count was 0.5×109/L, with 3% neutrophils, 1% blast forms and 96% lymphocytes. The hemoglobin was 84 g/L and the platelet count 87×109/L. Blood cultures were done and empirical broad-spectrum antimicrobial therapy (ticarcillin/clavulanate, tobramycin and vancomycin) begun. A bone marrow biopsy and computed tomography scan of the neck were performed. The lesion on the right cheek, which opened spontaneously on day 2, was swabbed and cultures were taken. What is the diagnosis?