Characteristics of Stenotrophomonas maltophilia infection in children in Sichuan, China, from 2010 to 2017.

Stenotrophomonas maltophilia (S. maltophilia) is an important nosocomial bacterial pathogen. However, the clinical features of children with S. maltophilia infection, the predisposing factors, and the antibiotic susceptibility of the bacteria have not been fully evaluated.In this study, the data of children with S. maltophilia infection from the West China Second University Hospital of Sichuan University (Chengdu, China) between July 2010 and October 2017 were collected and analyzed. The clinical features of enrolled children, the predisposing factors, and the antibiotic susceptibility were reported.In total, infection of S. maltophilia was identified in 128 patients. Most of these patients were under 1 year old (67.2%) and were mainly diagnosed as pneumonia (69%). A large proportion had underlying diseases (45.3%), received immunosuppressive therapy (53.1%), had undergone invasive operations (41.4%), had a history of carbapenem antibiotics use within 7 days before culture acquisition (54.7%), history of intensive care unit (ICU) hospitalization within previous 30 days (34.4%), and other risk factors. In particular, invasive operation (95% confidence interval [CI]: 1.125-14.324, P = .032), especially mechanical ventilation (95% CI: 1.277-20.469, P = .021), and ICU admission (95% CI: 1.743-22.956, P = .005) were independent risk factors for the children to develop severe S. maltophilia infection. As for antibiotic susceptibility, trimethoprim sulfamethoxazole (TMP-SMX), piperacillin tazobactam, ticarcillin clavulanate, and ceftazidime exhibited strong antibacterial activities against S. maltophilia, the susceptibility rates were 97.5%, 86.7%, 92.9%, and 81.5%, respectively.We report the clinical features of children with S. maltophilia infection, the predisposing factors and the antibiotic susceptibility. TMP-SMX can continue to be the first choice for the treatment of S. maltophilia infection. Piperacillin tazobactam, ticarcillin clavulanate, and the third generation cephalosporins can be used as alternative drugs.

Pseudomonas aeruginosa eradication therapy and risk of acquiring Aspergillus in young children with cystic fibrosis.

BACKGROUND: While Aspergillus detection rates in adults, adolescents and older children with cystic fibrosis (CF) have increased, the risk of acquiring this fungal pathogen in young children is unknown. AIM: To determine the risk and explanatory factors of acquiring Aspergillus in children with CF by age 5 years. METHODS: Cross-sectional analysis of clinical, bronchoalveolar lavage and treatment data from the Australasian Cystic Fibrosis Bronchoalveolar Lavage study was used to identify predictive factors for detecting Aspergillus at age 5 years. A parametric repeated time-to-event model quantitatively described the risk and factors associated with acquiring Aspergillus and Pseudomonas aeruginosa from birth until age 5 years. RESULTS: Cross-sectional analysis found that the number of P. aeruginosa eradication courses increased the odds of detecting Aspergillus at age 5 years (OR 1.61, 95% CI 1.23 to 2.12). The median (IQR) age for the first P. aeruginosa positive culture was 2.38 (1.32-3.79) years and 3.69 (1.68-4.74) years for the first Aspergillus positive culture. The risk of P. aeruginosa and Aspergillus events changes with time after the first year of study entry. It also decreases for P. aeruginosa after completing P. aeruginosa eradication (HR 0.15, 95% CI 0.00 to 0.79), but increases for Aspergillus events (HR 2.75, 95% CI 1.45 to 5.41). The risk of acquiring both types of events increases after having had a previous event. CONCLUSION: In young children with CF, completing P. aeruginosa eradication therapy and previous Aspergillus events are associated with increased risk of acquiring Aspergillus.

Achromobacter respiratory infections.

Achromobacteria are ubiquitous environmental organisms that may also become opportunistic pathogens in certain conditions, such as cystic fibrosis, hematologic and solid organ malignancies, renal failure, and certain immune deficiencies. Some members of this genus, such as xylosoxidans, cause primarily nosocomially acquired infections affecting multiple organ systems, including the respiratory tract, urinary tract, and, less commonly, the cardiovascular and central nervous systems. Despite an increasing number of published case reports and literature reviews suggesting a global increase in achromobacterial disease, most clinicians remain uncertain of the organism's significance when clinically isolated. Moreover, effective treatment can be challenging due to the organism's inherent and acquired multidrug resistance patterns. We reviewed all published cases to date of non-cystic fibrosis achromobacterial lung infections to better understand the organism's pathogenic potential and drug susceptibilities. We found that the majority of these cases were community acquired, typically presenting as pneumonias (88%), and were most frequent in individuals with hematologic and solid organ malignancies. Our findings also suggest that achromobacterial lung infections are difficult to treat, but respond well to extended-spectrum penicillins and cephalosporins, such as ticarcillin, piperacillin, and cefoperazone.

Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: II. cephalosporins and penicillins.

Acute pulmonary exacerbations (APE) are well-described complications of cystic fibrosis (CF) and are associated with progressive morbidity and mortality. Despite aggressive management with two or more intravenous anti-pseudomonal agents, approximately 25% of exacerbations will result in a loss of lung function. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti-pseudomonal cephalosporins (i.e., ceftazidime and cefepime) and penicillins (i.e., piperacillin-tazobactam and ticarcillin-clavulanate) in the treatment of APE and to identify areas where further study is warranted. The ceftazidime and cefepime dosing ranges from the literature are 200-400 mg/kg/day divided every 6-8 hr, maximum 8-12 g/day, and 150-200 mg/kg/day divided every 6-8 hr, up to 6-8 g/day, respectively. The literature supported dosing ranges for piperacillin and ticarcillin are 350-600 mg/kg/day divided every 4 hr, maximum 18-24 g/day of piperacillin component, and 400-750 mg/kg/day divided every 6 hr, up to 24-30 g/day of ticarcillin component, respectively. As a large portion of CF patients will not regain their lung function following an APE, we suggest the need to optimize antibiotic dosing and dosing regimens used to treat an APE in efforts to improve outcomes for CF patients infected with Pseudomonas aeruginosa. Future studies are needed to determine the clinical efficacy of higher than FDA-approved doses of ceftazidime, cefepime, and ticarcillin-clavulanate in APE. The usefulness of high dose piperacillin (>600 mg/kg/day) may be limited due to treatment-related adverse effects. Further understanding of these adverse effects in CF patients is needed.

Population pharmacokinetic and pharmacodynamic modeling of high-dose intermittent ticarcillin-clavulanate administration in pediatric cystic fibrosis patients.

BACKGROUND: The Intermountain Cystic Fibrosis Pediatric Center utilizes ticarcillin-clavulanate 400 mg/kg/d divided every 6 hours, (maximum 24 g/d). This dosing strategy is higher than the Food and Drug Administration (FDA)-approved package labeling. We evaluated the microbiologic efficacy of this dosing regimen. OBJECTIVES: The primary study objective was to predict the pharmacokinetic (PK) and pharmacodynamic (PD) MIC breakpoints (the highest MIC with a probability of target attainment [PTA] of at least 90%) for the bacteriostatic and bactericidal targets of ticarcillin activity against Pseudomonas aeruginosa using the study dosing regimen. A secondary objective was to evaluate the tolerability profile of the higher ticarcillin-clavulanate dosing regimen in children with cystic fibrosis (CF). METHODS: This was a population-based PK-PD modeling study of pediatric CF patients admitted from January 1, 2005 to December 31, 2009 who received the dosing regimen for at least 7 days. Population PK and PD models were used to estimate PK and PD parameters for 127 clinically evaluable patients. A 10,000-patient Monte Carlo simulation was performed to estimate the target time in which free drug concentrations exceeded the MIC of the infecting organism. The 2 PK-PD targets of microbiologic efficacy included ≥30% for bacteriostasis and ≥50% for bactericidal effects of ticarcillin-clavulanate at higher than FDA-approved doses. RESULTS: A total of 127 patients (age, 0-19 years) met inclusion criteria. Serum concentration levels were modeled in this patient population using published PK parameters with intermittent ticarcillin peak concentrations reaching 288 (93.4) mg/L. The model predicted the PTA of the MICs for P. aeruginosa with a near-maximal bactericidal PK-PD MIC breakpoint of 16 µg/mL and a bacteriostasis PK-PD MIC breakpoint of 32 µg/mL. CONCLUSIONS: The results of our simulation suggest that in this select pediatric population, higher than FDA-approved doses of ticarcillin-clavulanate were effective in achieving bactericidal effects among pseudomonal isolates with MICs <16 µg/mL. Bacteriostatic and bactericidal effects were not frequently achieved among P. aeruginosa isolates with MICs >32 µg/mL. Additional studies are warranted to determine the clinical effectiveness of this dosing regimen.

A prospective study of cefepime versus ticarcilline/clavulanate as empirical treatment of febrile neutropenia in lymphoma patients.

OBJECTIVE: To check the effectiveness of ticarcillin clavulanate versus cefepime as monotherapy in febrile neutropenia in lymphoma patients and also to check tolerability profile of both drugs. METHODS: We randomly assigned 107 neutropenic patients to receive either cefepime or ticarcillin/clavulanate. The clinical efficacy and tolerability profile of both drugs were compared using either cefepime or ticarcillin clavulanate (TC) as an empirical treatment for management of febrile neutropenia in lymphoma patients only with same characteristics at time of presentation. RESULTS: A significant difference in efficacy of the two treatment arms was noted. A successful outcome was reported with 28 (51%) out of 55 in cefepime arm compared to 16 (42%) out of 52 patients in ticarcillin/clavulanate group (p = 0.35; 95% Confidence). The distribution of time for defervesence was estimated for each treatment group and a trend to a shorter time for defervesence was found in the CEFEPIME group (48.4 hour for cefepime, 58.28 hour for TC group; p = 0.018). For microbiologically documented infections, the successful eradication rate was 49% (6 of 14 patients) for TC group as compared to 83% (10 of 12 patients) for cefepime group. This difference was statistically significant for microbiologically documented infections. Twenty seven (52%) patients of TC group and 19 (35%) of cefepime group required modifications of antibiotic regimen. The most frequent modifications consisted of the addition of either an amino glycoside (amikacin) or glycopeptides (vancomycin). CONCLUSION: CEFEPIME regimen was more effective than TC regimen, with a consistent trend toward a better outcome associated with cefepime compared to Ticarcillin/clavulanate.

Clinical profile of adult cystic fibrosis patients with frequent epidemic clones of Pseudomonas aeruginosa.

BACKGROUND AND OBJECTIVE: Earlier reports suggested that Pseudomonas aeruginosa frequent epidemic clones circulating in cystic fibrosis (CF) centres had increased virulence. However, recent data show no consistent associations with virulence, and suggest attenuation of virulence in chronic infection. Changes to infection control programmes in relation to frequent epidemic clones should be based on their frequency, virulence across all age groups and mode of acquisition. The Australian epidemic strain-1 (AES-1) (or the Melbourne epidemic strain) and AES-2 are common in CF clinics in mainland eastern Australia, but not in the environment. Both have shown increased virulence, but there are no data specifically in adults. This study examines the frequency and virulence of P. aeruginosa frequent epidemic clones in the adult CF clinic at Royal Prince Alfred Hospital, Sydney, Australia. METHODS: Two hundred and fifty-eight P. aeruginosa isolates from 112 participants were genotyped by pulsed field gel electrophoresis. Ninety-eight patients were followed up for 1 year and associations sought between infection with a frequent epidemic clone, clinical outcome and antibiotic resistance. RESULTS: Four frequent P. aeruginosa epidemic clones (AES-1, AES-2, S-1, S-2) affected almost 50% of participants. AES-1 predominated (38%). AES-1, AES-2 and S-1 were associated with increased exacerbations and hospital-admission days. AES-1 showed increased resistance to aminoglycosides and ticarcillin-clavulanate. CONCLUSIONS: This study supports the potential threat of frequent P. aeruginosa epidemic clones in adult CF populations.

[Infectious keratitis and cosmetic lenses: a five-case retrospective study]. / Kératites infectieuses et lentilles cosmétiques : étude rétrospective de cinq cas.

PURPOSE: To determine the characteristics of infectious keratitis related to plano cosmetic lenses. METHODS: Retrospective case study of a series of infectious keratitis among plano cosmetic lenses wearers. The main parameters were demographic data, medical history, risk factors for infectious complications and keratitis severity criteria, microbiological results, clinical course, and final visual acuity. RESULTS: Five patients were included, all females, ranging from 15 to 50 years of age. Four were emmetropic. One patient had undergone refractive photokeratectomy a few months before. All had risk factors for infectious complications. The fundamental causes of infections were diverse: bacterial abscesses, keratomycosis, and amoebic keratitis. All presented severity criteria. In two cases, the keratitis led to severe consequences with legal blindness requiring penetrating keratoplasty in one case. DISCUSSION: Infectious keratitis in plano cosmetic lenses wearers is not rare and may have dramatic consequences. Sales are specifically regulated and the lenses are considered cosmetic products, not medical devices. The sales regulations for plano cosmetic lenses should be updated, as several countries have already done after encountering many serious incidents.

A hot, swollen joint in a cirrhotic patient.

Septic arthritis in the elderly carries a high mortality. Underlying risk factors, such as diabetes, malignancy, chronic renal failure, rheumatoid arthritis, hepatobiliary disease and AIDS, should be assessed. Rare causative organisms are occasionally encountered. Here, we describe a case of an 80-year-old diabetic patient with liver cirrhosis who developed Klebsiella pneumoniae septic arthritis, which is a rare cause of joint infection. We postulate that this case supports the notion that the patient's knee effusion seeded during a primary K pneumoniae bacteraemia of intestinal origin and related to liver cirrhosis.

The costs of treatment of early and chronic Pseudomonas aeruginosa infection in cystic fibrosis patients.

The aim of cystic fibrosis (CF) care is to improve both the life expectancy and quality of life of patients. However, rising costs and limited resources of health services must be taken into account. There are many different antibiotic strategies for therapy of Pseudomonas aeruginosa infection in CF patients. In this 5-year retrospective study we found that the cost of treatment of initial infection is considerably lower than the cost of treating chronic P. aeruginosa infections. The percentage distribution of costs of antibiotic treatment in relationship to the administration route was considerably different between outpatients and inpatients. We observed an increase in antibiotic costs with the age of the patient and the decrease in FEV(1)values. The implementation of early eradication treatment, in addition to decreasing the prevalence of patients chronically infected by P. aeruginosa, might also bring about a notable decrease in costs.

Ertapenem or ticarcillin/clavulanate for the treatment of intra-abdominal infections or acute pelvic infections in pediatric patients.

BACKGROUND: Ertapenem, a group I carbapenem antibiotic, has been shown to be safe and effective in treating adults with complicated intra-abdominal (cIAI) or acute pelvic infection (API). This study evaluated ertapenem for treating these infections in children. METHODS: In an open-label study, children aged 2 to 17 years with cIAI or API were randomized 3:1 to receive ertapenem or ticarcillin/clavulanate. Children 13 to 17 years of age received 1 g parenterally daily, and those 2 to 12 years of age received 15 mg/kg twice daily. Patients < 60 kg received ticarcillin/clavulanate 50 mg/kg 4 to 6 times daily and 3.1 g 4 to 6 times daily for those > or = 60 kg. Patients were assessed for safety and tolerability throughout the study and for efficacy after the completion of therapy. RESULTS: One hundred five patients, 72 (69%) with cIAI, received > or = 1 dose of study drug and were included in the safety analysis. Eighty-one patients were treated with ertapenem. Infusion site pain was the most common drug-related adverse event in both groups. In the modified intent-to-treat analysis, the age-adjusted posttreatment clinical response rates were 87% (43/50 patients) and 100% (25/25 patients) in the cIAI and API patients, respectively, for ertapenem and 73% (11/15 evaluable patients) and 100% (8/8 evaluable patients), respectively, for ticarcillin/clavulanate. Overall age-adjusted response rates were 91% (68/75 evaluable patients) for ertapenem and 83% (19/23 evaluable patients) for the comparator. CONCLUSIONS: This study suggests that ertapenem is generally safe and efficacious for treating cIAI or API in pediatric patients.

Outpatient intravenous antibiotics for methicillin-resistant Staphylococcus aureus sinusitis.

BACKGROUND: The widespread use of broad-spectrum antibiotics has resulted in an increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA). Its presence in sinonasal cultures in patients with sinusitis suggests its pathogenicity. However, the efficacy and safety of treatment modalities for MRSA sinusitis remain incompletely described. METHODS: A retrospective chart review of six patients treated for MRSA sinusitis with outpatient intravenous (i.v.) antibiotics was performed for patient demographics, history of antibiotic use, history of prior sinus surgery, and treatment-related complications. A quality-of-life survey and endoscopically guided cultures before and after therapy were used to measure treatment outcomes. RESULTS: The cohort consisted of five women and one man with a mean age of 50.8 years. All patients had undergone multiple sinus procedures with a mean number of 2.7 procedures per patient (range, 1-6 procedures). Five patients (83.3%) experienced negative cultures after outpatient i.v. antibiotics. The single patient who had persistent cultures experienced clinical and endoscopic improvement in her symptoms. The quality-of-life scores improved in five of the six patients (83.3%) after therapy. Four patients (66.7%) experienced five adverse events including allergic reaction (four events) and neutropenia (one event), all of which resolved with a change in medication. CONCLUSION: Outpatient i.v. antibiotics may be an effective therapy for the treatment of MRSA sinusitis. The occurrence of adverse events requires a dedicated protocol to therapy. Future studies are required to investigate long-term efficacy.

The value of a CT-guided fine needle aspirate in infants with lung abscess.

OBJECTIVE: To describe the range of pathogens isolated from a lung abscess in infants less than one year of age. To assess the role of direct culture from the abscess. METHODS: The two index cases were managed in 2002. An institution-based review was conducted of all infants up to one year of age diagnosed with a lung abscess between 1989 and 2002. Data sources were hospital's disease index and Neonatal Intensive Care Unit Audit database using ICD9 and ICD10 diagnostic codes for 'lung abscess'. RESULTS: Five infants, under the age of one year, were treated for a lung abscess. In the one case where the abscess was left-sided it was associated with a congenital cystic adenomatoid malformation of the lung. Pathogens were isolated following direct culture of the abscess in four cases. In three cases a single pathogen was isolated: pseudomonas aeruginosa, staphylococcus aureus and haemophilus influenzae. In one case a mixture of escherichia coli, streptococcus milleri and an anaerobe, propionibacteria, were cultured. Antibiotic therapy was directed at the identified pathogen(s) in all four cases. There was no mortality or recurrence. CONCLUSION: Predisposing factors for a lung abscess in infancy include prematurity, assisted ventilation, congenital lung anomaly and aspiration. Given the range of potential pathogens, direct culture by CT-guided fine needle aspiration is recommended to direct appropriate intravenous medical therapy provided the abscess is located peripherally.

Cefepime versus ticarcillin and clavulanate potassium and aztreonam for febrile neutropenia therapy in high-dose chemotherapy patients.

An open labeled randomized trial comparing the efficacy and cost of empirically applied cefepime (C) as monotherapy versus combination therapy consisting of ticarcillin and clavulanate potassium and aztreonam (T/A) was performed in febrile neutropenic patients following high-dose chemotherapy (HDC) +/- radiation, with or without peripheral blood stem cell support. Over a 28-month period, 126 patients were screened and included in the study. Using afebrile status following 3 days of therapy as a primary endpoint, both regimens produced comparable clinical response rates (C = 55% vs. T/A = 61%). Also, the use of vancomycin for resistant gram-positive infections and alteration of gram-negative infection coverage was similar in both groups (C = 40% vs. T/A = 47% and C = 29% vs. T/A = 24%). Both treatment groups had similar needs for empirical antifungal therapy (C = 25% vs. T/A = 22%). There was a postrandomization difference between the two groups in that the "C" group had a significantly higher number of allogeneic transplants and non-stem-cell-supported patients, whereas the "T/A" group had a significantly greater number of autologous peripheral blood stem cell patients (p < 0.0001). Despite this difference, the C group had a significantly lower cost ratio than the T/A group (p = 0.016). In conclusion, we have shown that C treatment of febrile neutropenic patients following HDC results in similar efficacy and lower cost when compared to T/A, despite the inclusion of higher risk patients in the C group.

Late bacterial keratitis after implantation of intrastromal corneal ring segments.

We report a case of bacterial keratitis that occurred after implantation of intrastromal corneal ring segments (Intacs). The patient presented with decreased vision, inflammation, and stromal infiltrates localized at the extremity of an Intacs channel 3 months after surgery. Culture were positive for Clostridium perfringens and Staphylococcus epidermidis. The infiltrates progressed despite treatment with topical fortified and systemic antibiotics. The Intacs were removed. The keratitis slowly resolved, and the patient recovered a best corrected visual acuity of 20/20.

Agrobacterium radiobacter bacteremia in pediatric patients: case report and review.

Agrobacterium radiobacter is an opportunistic pathogen often associated with indwelling catheters. We report five children with central venous catheter-associated A. radiobacter bacteremia and review the characteristics of pediatric Agrobacterium infections. Cure was achieved with appropriate antibiotics, often ticarcillin-clavulanate and gentamicin, and removal of the catheter.

[Hepatic inflammatory pseudotumor regressing with antibiotic therapy]. / Pseudo-tumeur inflammatoire hépatique régressant sous antibiothérapie.

INTRODUCTION: Inflammatory hepatic pseudo-tumors are rare, non-neoplastic lesions, and their diagnosis is usually made on hepatectomy samples. OBSERVATION: The general health of a 77 year-old patient was suddenly altered and clinical examination (and scan) revealed a hepatic tumor. Diagnosis of inflammatory hepatic pseudo-tumor was evoked by analysis of a biopsy. In view of the age and the general state of the patient we chose prolonged antibiotic therapy rather than hepatic surgery. Nine months later, the tumor had regressed. COMMENTS: Because they are rare (100 cases described), hepatic pseudo-tumors raise two questions: can diagnosis be made simply by biopsy or should one always analyze the complete sample and, if hepatectomy is contraindicated, is non-surgical treatment effective? The progression of our patient permits us to reply positively to both questions.

Severe cellulitis/myositis caused by Stenotrophomonas maltophilia.

OBJECTIVE: To present a case of cellulitis/myositis due to Stenotrophomonas maltophilia in the absence of trauma and to discuss a potentially novel treatment option. CASE SUMMARY: A 57-year-old white man, having undergone an allogeneic bone marrow transplant, developed myositis with S. maltophilia of the left soleus muscle; there had been no trauma. Risk factors for infection included neutropenia, prolonged hospitalization and intensive care unit stay, and broad-spectrum antibiotic exposure. The affected area of muscle was resected and the patient successfully treated with trimethoprim/sulfamethoxazole (TMP/SMX), ticarcillin/clavulanate, and aztreonam. DISCUSSION: In severe myositis/cellulitis caused by S. maltophilia, TMP/SMX is considered the drug of choice. However, bacteriostatic agents such as TMP/SMX are less than ideal in neutropenic patients. The combination of ticarcillin/clavulanate plus aztreonam has been shown to improve activity in vitro against this organism compared with TMP/SMX. This is likely due to inhibition of the 2 beta-lactamases this organism produces by clavulanate and aztreonam. In our study of clinical isolates of S. maltophilia, this combination reduced the minimum inhibitory concentration at 90% by 128-fold and was synergistic against 10 of 12 isolates tested in time-kill analysis. CONCLUSIONS: S. maltophilia is emerging as an important pathogen in patients with compromised immunity, leading to severe infections that are difficult to treat. Based on in vitro synergy studied, we recommend considering ticarcillin/clavulanate plus aztreonam as a potential treatment option in immunocompromised patients with S. maltophilia infection.

Acute epiglottitis: a review of 80 patients.

We reviewed 80 patients admitted to our hospital who were diagnosed with acute epiglottitis between January 1995 and March 1999, and their clinical features, evolution and treatments were analysed. No sexual predominance was found, and there was no patient younger than 16 years of age. The patient fatality rate was 1.3 per cent, and the hospitalization period was markedly longer than those of other reports.