Clinical Resolution Of Infection Research Articles

Carbapenem-Resistant Acinetobacter spp Infection in Critically Ill Patients With Limited Treatment Options: A Descriptive Study of Cefiderocol Therapy During the COVID-19 Pandemic.

Carbapenem-resistant Acinetobacter baumannii infections are difficult to treat and are a significant public health threat due to intrinsic/acquired resistance and limited treatment options. A retrospective, observational cohort study in patients receiving cefiderocol via Shionogi's early access program for Acinetobacter spp infections (1 April 2020-30 April 2021; 27 sites; Italy, Spain, Germany, France). Primary outcome was clinical success, defined as clinical resolution of infection at day 14 or day 28 survival. Overall, 147 patients were included. Primary infection sites were respiratory (65.3%) and bloodstream (unknown source [15.6%]; catheter-related [10.9%]); 24.5% of patients had polymicrobial infection. Of 136 patients in intensive care (92.5%), 85.3% (116/136) received mechanical ventilation. Septic shock (55.6% [70/126]) and coronavirus disease 2019 (COVID-19) (81.6%) were prevalent. Prior to cefiderocol, 85.0% of patients received gram-negative treatment, 61.2% received ≥2 antimicrobials, and most received colistin (58.5%; median duration, 11.5 days). Cefiderocol monotherapy was used in 30.6% of patients. Clinical success rate was 53.1% and was higher in patients without septic shock (62.5%), without COVID-19 (77.8%), and with lower Sequential Organ Failure Assessment (SOFA) scores (quartile 1 [median, 3; range, 0-5]: 82.9%). Day 28 survival was 44.9% and was higher in patients without septic shock (60.7%), without COVID-19 (59.3%), with lower SOFA score (quartile 1: 82.9%), and receiving first-line cefiderocol (68.2% [15/22]). Resolution of infection at day 14 occurred in 39.5% of patients. Despite use in complex patients with limited treatment options and high septic shock/COVID-19 rates, cefiderocol treatment was associated with an overall clinical success rate of 53%.

Persistent Lung Inflammation After Clinical Resolution of Community-Acquired Pneumonia as Measured by 18FDG-PET/CT Imaging

Survivors of community-acquired pneumonia (CAP) are at increased risk of cardiovascular disease, cognitive and functional decline, and death, but the mechanisms remain unknown. Do CAP survivors have evidence of increased inflammatory activity in their lung parenchyma on 2-deoxy-2-[18F]fluoro-d-glucose (18FDG)-PET/CT imaging after clinical resolution of infection? We obtained 18FDG-PET/CT scans from 22 CAP survivors during their hospitalization with pneumonia (acute CAP) and 30 to 45days after hospital discharge (post-CAP). In each set of scans, we assessed the lungs for foci of increased 18FDG uptake by visual interpretation and by total pulmonary glycolytic activity (tPGA), a background-corrected measure of total metabolic activity (as measured by 18FDG uptake). We also measured, post-CAP, the glycolytic activity of CAP survivor lung areas with volumes similar to the areas in 28 matched historical control subjects without pneumonia. Overall, 68%of CAP survivors (95%CI, 45%-85%) had distinct residual areas of increased 18FDG uptake in their post-CAP studies. tPGA decreased from 821.5 (SD, 1,140.2) in the acute CAP period to 80.0 (SD, 81.4) in the post-CAP period (P= .006). The tPGA post-CAP was significantly higher than that in lung areas of similar volume in control subjects (80.0 [SD, 81.4] vs-19.4 [SD, 5.9]; P< .001). An important proportion of CAP survivors have persistent pulmonary foci of increased inflammatory activity beyond resolution of their infection. As inflammation contributes to cardiovascular disease, cognitive decline, functional waning, and mortality risk in the general population, this finding provides a plausible mechanism for the increased morbidity and mortality that have been observed post-CAP.

Identification and Characterization of Burkholderia pseudomallei from Localized Pyogenic Infections in Eastern India: A Clinico-Microbiological Study.

Melioidosis, caused by Burkholderia pseudomallei, is increasingly recognized in several regions of the globe. The present study was performed to identify and determine the frequency of B. pseudomallei infection in localized pyogenic lesions in eastern India and describe their clinico-microbiological profile. Pus samples were subjected to standard microbiological techniques for isolation and identification of various bacteria, including B. pseudomallei, which were confirmed by PCR. The clinical and demographic details of patients with melioidosis and antimicrobial susceptibility pattern of B. pseudomallei isolates were analyzed. Of 245 samples, 126 (51.4%) were culture positive, yielding 137 isolates. Staphylococcus aureus was the predominant pathogen accounting for 54 (39.4%) isolates, followed by B. pseudomallei accounting for 34 (24.8%) isolates. The mean age of the patients with melioidosis was 39.1 years, with males (24/34; 70.6%) being affected more than females (10/34; 29.4%). A majority of the patients were laborers (12/34; 35.3), followed by homemakers (8/34; 23.5%). Head and neck abscesses (35.3%) were the most common presentation followed by pyogenic lesions of the musculoskeletal system (32.3%) and deep organ abscesses (23.5%). Clinical resolution of infection was observed in 31 (91.2%) patients, relapse in two (5.9%) patients, and death in one (2.9%) patient, respectively. Susceptibility testing revealed all B. pseudomallei isolates to be completely susceptible to the following antimicrobials: ceftazidime, trimethoprim-sulfamethoxazole, imipenem, and doxycycline, with one (2.9%) resistant to amoxicillin-clavulanic acid. Burkholderia pseudomallei is an emerging etiological agent of localized pyogenic infections in eastern India, affecting a mainly adult male population. An increased vigilance along with appropriate diagnostic techniques helps in accurate diagnosis facilitating appropriate therapy.

Species-Specific Immunoassay for Diagnosis and Tracking Treatment Response in Foot and Ankle Infection

Category:Basic Sciences/Biologics; DiabetesIntroduction/Purpose:Staphylococcus aureus is the major pathogen foot and ankle infections and osteomyelitis (>50%). There are currently no sensitive and specific diagnostic tools for monitoring a pathogen’s ongoing infection or providing prognostic measures. We have developed a novel immunoassay for S. aureus, and have applied this to diagnose and monitor its infectivity. We hypothesize that: 1) the species-specific immunoassay can serve as a reliable diagnostic tool for S. aureus foot and ankle infections and 2) the immunoassay provides a measure of treatment response and prognosis of clinical outcome to antibiotics therapy for S. aureus foot and ankle infections.Methods:From July 2015 to July 2019, 83 infected diabetic foot ulcer (DFU) patients undertaking surgical treatment were recruited. Blood were drawn from subjects at initial, 4-week, 8-week, and 12-week after surgery. Clinical wound healing status was determined by a fellowship-trained orthopaedic foot and ankle surgeon. Serum antibodies and plasmablast cultured antibodies (newly synthesized antibodies: NSA) were harvested. Eight unique S. aureusantigens from distinct functional classes were used for the immunoassay. All serum and NSA samples were run on a flow cytometer (Bio-Plex 200; Bio-Rad, Life Sciences Research) in duplicates and assessed for predictive ability in discriminating infection status and healing status using receiver operating characteristic (ROC) curve analysis, with accuracy summarized by the area under the ROC curve (AUC). Nonparametric estimates and 95% confidence intervals for the AUC were computed for each predictor along with p-values for testing the significance of each AUC.Results:Analysis of serum immunoassay showed significant difference in three anti-S. aureus antigens titers (IsdH (p = 0.037; AUC = 0.638), ClfB (p = 0.025; AUC = 0.644), and SCIN (p = 0.005; AUC = 0.677)) between S. aureus infected versus non- S. aureus infected DFU patients at initial presentation. NSA immunoassay showed elevation of two different S. aureus specific antigens, IsdH and LukS-PV, for S. aureus infected versus non- S. aureus infected DFU patients in ratios of approximately five and four, respectively. Changes of NSA based anti-S. aureus antibody titers over 12 weeks period, as single antigen or in combination, significantly correlated with clinical resolution of infection and wound healing status. Four anti-S. aureus antigen combinations achieved the highest AUC (Figure 1).Conclusion:Our results demonstrate that both the serum and NSA immunoassay can diagnose S. aureus infected DFUs. Furthermore, changes in NSA titers over a period of time against various S. aureus specific antigens significantly correlated with clinical representation of infection and wound healing status. The novel species-specific immunoassay can serve as a promising diagnostic system, tracking tool and prognostic potential in management of S. aureus associated foot and ankle infection.

Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection

SUMMARYBacteria adapt to dynamic changes in the host during chronic and recurrent infections. Bacterial microevolution is one type of adaptation that imparts a selective advantage. We hypothesize that recurrent episodes of disease promote microevolution through genetic mutations that modulate disease severity. We use a pre-clinical model of otitis media (OM) to determine the potential role for microevolution of nontypeable Haemophilus influenzae (NTHI) during sequential episodes of disease. Whole genome sequencing reveals microevolution of hemoglobin binding and lipooligosaccharide (LOS) biosynthesis genes, suggesting that adaptation of these systems is critical for infection. These OM-adapted strains promote increased biofilm formation, inflammation, stromal fibrosis, and an increased propensity to form intracellular bacterial communities (IBCs). Remarkably, IBCs remain for at least one month following clinical resolution of infection, suggesting an intracellular reservoir as a nidus for recurrent OM. Additional approaches for therapeutic design tailored to combat this burdensome disease will arise from these studies.

Follow-Up Study: One-Step Salvage of Infected Prosthetic Breast Reconstructions Using Antibiotic-Impregnated Polymethylmethacrylate Plates and Concurrent Tissue Expander Exchange.

Periprosthetic infections represent major complications in breast reconstruction, frequently leading to expander-implant loss. No consensus regarding a management algorithm for attempted salvage currently exists. This study assessed outcomes of the authors' salvage protocol using an antibiotic-impregnated polymethylmethacrylate implant with expander device exchange. A retrospective chart review identified infected implant-based breast reconstruction cases treated between 2009 and 2017. Of 626 cases initially identified, a total of 62 cases had severe prosthetic infections, and underwent either prosthetic salvage (n = 45) or immediate explantation (n = 17). All the prosthetic salvage patients received intravenous antibiotics followed by surgical débridement, insertion of polymethylmethacrylate plates, device exchange, and postoperative antibiotics. After clinical resolution of infection, tissue expansion was performed, with the polymethylmethacrylate plates remaining in situ until exchanged for permanent implants. The authors' study demonstrated a primary infection clearance rate of 82.2 percent (n = 37). Compared to the traditional explantation group, a significantly higher percentage of the salvage patients completed final reconstruction (84.4 percent versus 35.3 percent; p < 0.001). Fewer patients abandoned reconstruction efforts after infection clearance (2.2 percent versus 58.8 percent; p < 0.001). The majority of cases (78.8 percent) that succeeded the salvage protocol ultimately received implant-based reconstruction; 62.5 percent that failed the salvage protocol still went on to receive autologous tissue reconstruction. Sustained local antibiotic delivery using polymethylmethacrylate implants and expander device exchange can successfully salvage an infected breast expander/implant. Compared with the traditional explantation approach, more patients complete final reconstruction. Other benefits include preserved skin envelope integrity and possibly improved long-term aesthetic outcomes. Therapeutic, III.

Safety and Efficacy of Bacteriophage Therapy in Lung Transplant Candidates and Recipients

Purpose Bacteriophage therapy (BT) employs lytic bacteriophages to treat pathogenic bacteria. Although BT is an emerging strategy against multidrug-resistant (MDR) infections, experience in solid organ transplant is limited. We describe BT in four lung transplant candidates and recipients with life-threatening MDR infections, including Pseudomonas aeruginosa (PsA) (n=3) and Burkholderia dolosa (n=1) Methods For each patient, lytic bacteriophages were selected against their bacterial isolates (Table 1). Intravenous (IV) bacteriophage was administered for variable durations under individual emergency Investigational New Drug applications and with patient informed consent. Safety was assessed using clinical and laboratory parameters and efficacy was based on clinical resolution of infection. All patients received concurrent antibiotics. Results One lung transplant candidate and three recipients received BT. The transplant candidate had developed acute kidney injury (AKI) on IV colistin for MDR PsA prompting adjunctive BT administration. Following BT, colistin was discontinued, oxygen requirements improved, AKI resolved, and she went on to lung transplant. Two ventilator dependent recipients with refractory MDR PsA pneumonia despite antibiotic therapy and multiple pulmonary procedures to mitigate airway complications also received BT therapy. Both patients were weaned from mechanical ventilation prior to hospital discharge. A fourth patient had recurrent B. dolosa infection following transplant despite IV antibiotic therapy. Following BT initiation consolidative opacities improved and ventilator weaning was begun. There were no treatment-related adverse events reported in the four cases. Conclusion BT was well-tolerated and was associated with clinical efficacy when used as an adjunct to antibiotics in patients who were not responsive to antibiotics alone. Bacteriophage therapy may be a viable adjunct to antibiotics in the era of increasing antimicrobial resistance.

Literature Review of Saccharomyces boulardii in the Treatment of Refractory Recurrent Clostridium difficile Infection

&lt;p&gt;Objective: To evaluate the efficacy of S. boulardii for the treatment of recurrent C. difficile infections.&lt;/p&gt;&lt;p&gt;Methods: Eligible articles included S. boulardii in patients with recurrent C. difficile infection. The primary endpoint examined was clinical resolution of infection with no further recurrences during follow-up.&lt;/p&gt;&lt;p&gt;Results: Six studies met inclusion criteria. A case report showed resolution of recurrences in one patient, and an experimental trial showed a trend towards decreased recurrences in patients receiving S. boulardii (85% no further recurrences). Two randomized controlled trials found a significant decrease in recurrences for S. boulardii versus placebo (34.6% vs 64.7%, P=0.04; 16.7% vs 50%, P=0.05). One meta-analysis determined significant efficacy for S. boulardii in reducing relapses (RR 0.59, 95% CI 0.35-0.98), while another concluded there was insufficient evidence to recommend probiotics for C. difficile infection.&lt;/p&gt;&lt;p&gt;Conclusions: S. boulardii may be considered for patients with recurrent C. difficile infection, refractory to antibiotic regimens alone.&lt;/p&gt;

One-Step Salvage of Infected Prosthetic Breast Reconstructions Using Antibiotic-Impregnated Polymethylmethacrylate Plates and Concurrent Tissue Expander Exchange.

Periprosthetic infection represents a major complication in breast reconstruction, frequently leading to expander-implant loss. Recent studies report variable success in the salvage of infected breast prostheses through systemic antibiotic therapy and surgical intervention. There is currently no consensus regarding a management algorithm for attempted salvage. The purpose of this pilot study was to evaluate the early outcomes of a protocol using antibiotic-impregnated polymethylmethacrylate (PMMA) implant placement with expander device exchange. A retrospective database was queried to identify all patients with infected implant-based breast reconstruction who were treated by the study authors and who underwent attempted salvage under the study protocol. All patients received intravenous antibiotics followed by surgical debridement of the infected pocket, insertion of antibiotic-impregnated PMMA plates and/or beads, device exchange, and postoperative antibiotics. After clinical resolution of infection, tissue expansion was performed with the PMMA implants remaining in situ until exchanged to permanent implants. All patients with infected prosthetic breast reconstructions achieved implant pocket sterilization using this method. At a mean follow-up of 8.2 months (range, 1-19 months), none of these patients have required reoperation for capsular contracture. One patient, while under treatment with prednisone for a rash, developed recurrent infection, which led to explantation of her implant. Two patients underwent radiation therapy while an antibiotic plate and tissue expander were in place, with no observed exposure or infection recurrence. Sustained local antibiotic delivery using PMMA implants and expander device exchange can successfully salvage an infected breast implant. Perceived benefits include shorter time to completed reconstruction, preserved skin envelope integrity, and possibly improved long-term aesthetic outcomes.

Use of permanently placed metal expandable cages for vertebral body reconstruction in the surgical treatment of spondylodiscitis.

This is a retrospective study of 15 patients treated for spondylodiscitis with implanted metal cages. The purpose of this study is to investigate the outcomes of patients treated with permanently placed metal hardware in vertebral body reconstruction for spondylodiscitis. The use of metal implants in the face of infection has classically been discouraged in orthopedic literature because of the ability of bacteria to form biofilms on metal surfaces. Traditional treatment of spondylodiscitis has been aggressive debridement followed by reconstruction with bone grafts. Expandable metallic cages made reconstruction of these defects significantly easier. However, concern exists that metallic implants affect the resolution of infection. A search of the authors' patient database from 2005 to 2009 revealed 21 patients with spondylodiscitis treated with anterior debridement and reconstruction with an expandable metallic cage. Fourteen patients (15 cases) had sufficient documented clinical follow-up and were available for review. Resolution of infection was determined by evaluating symptoms, laboratory data, and final radiographic result. Of the 15 cases, all had clinical resolution of infection with an average follow-up time of 25 months. An average loss of 1.9° of correction was observed when comparing final follow-up radiographs with initial postoperative radiographs. Radiograph review revealed no extensive osteolysis around the hardware or progressive collapse. These results suggest that the use of expandable metal cages maintains alignment while not perpetuating infection. The spine appears to provide a unique environment that permits the use of metal implants in the setting of infection.

Dose of Trimethoprim-Sulfamethoxazole To Treat Skin and Skin Structure Infections Caused by Methicillin-Resistant Staphylococcus aureus

We undertook this study to investigate whether treatment with a higher dose of trimethoprim-sulfamethoxazole (TMP/SMX) led to greater clinical resolution in patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA). A prospective, observational cohort with nested case-control study was performed at a public tertiary health system. Among patients with MRSA SSTIs during the period from May 2008 to September 2008 who received oral monotherapy with TMP/SMX and whose clinical outcome was known, the clinical characteristics and outcomes were compared between patients treated with a high dose of TMP/SMX (320 mg/1,600 mg twice daily) for 7 to 15 days and patients treated with the standard dose of TMP/SMX (160 mg/800 mg twice daily) for 7 to 15 days. In patients with MRSA SSTIs, those treated with the high dose of TMP/SMX (n = 121) had clinical characteristics similar to those of patients treated with the standard dose of TMP/SMX (n = 170). The only exception was a higher proportion of patients with a history of trauma upon admission among the patients treated with the higher dose. The proportion of patients with clinical resolution of infection was not different in the two groups (88/121 [73%] versus 127/170 [75%]; P = 0.79). The lack of significance remained in patients with abscess upon stratified analysis by whether surgical drainage was performed. The study found that patients with MRSA SSTIs treated with the higher dose of TMP/SMX (320/1,600 mg twice daily) for 7 to 15 days had a similar rate of clinical resolution as patients treated with the standard dose of TMP/SMX (160/800 mg twice daily) for 7 to 15 days.

An Uncommon Infection In An Uncommon Host

We present the case of an international traveller who was eventually diagnosed with amoebiasis and autosomal dominant polycystic kidney disease (ADPKD) after she presented with recurring fevers. The patient was also diagnosed with non-amoebic bacterial hepatitis. Positron emission tomography (PET) can play an important role in locating the source of infection in patients with ADPKD when hepatic or renal infection is suspected. It can also be used to document clinical resolution of infection in difficult cases. Hepatic parenchymal infections in ADPKD patients may warrant a prolonged course of rotating antibiotics.

Antimicrobial delivery by intrasynovial catheterisation with systemic administration for equine synovial trauma and sepsis

To present the technique for intra-articular catheter placement and report the clinical outcomes of 38 cases of equine synovial trauma and/or infection treated with broad-spectrum antimicrobials administered via an intrasynovial catheter (ISC). Retrospective study. Medical records of 38 horses treated for synovial trauma and sepsis with frequent antimicrobial administration through an ISC from 1995 to 2008 were reviewed. Follow-up information was obtained via clinical re-evaluation or telephone contact with the owners. The majority of horses (84%) received amikacin and Timentin(R) four times daily. In addition, synovial lavage through the ISC was carried out in 27 horses (71%). Only radiological evidence of osteolysis had a significant negative impact on both lameness at the time of hospital discharge and the long-term outcome. In total, 92% of horses treated with frequent antimicrobial administration through an ISC had clinical resolution of infection. Catheter obstruction occurred in three cases, necessitating replacement or removal, and two synovial fistulae developed at sites of open drainage. The majority of horses treated had a favourable outcome, with 86% being at least pasture sound and 43% returned to riding. Septic synovial structures treated with frequent antimicrobial administration through an ISC had a good prognosis for survival and 43% returned to riding, which is consistent with the results of other studies. The use of a simple ISC should be considered when broad-spectrum intrasynovial antimicrobial administration and lavage of a septic synovial structure are indicated.

Splenic Rupture and Malignant Mediterranean Spotted Fever

Splenic Rupture and Malignant Mediterranean Spotted Fever

Randomized, Investigator-Blinded, Multicenter, Comparative Study of Gatifloxacin Versus Amoxicillin/Clavulanate in Recurrent Otitis Media and Acute Otitis Media Treatment Failure in Children

Recurrent otitis media and acute otitis media treatment failure are commonly encountered in the pediatric population. To compare the clinical efficacy of gatifloxacin with amoxicillin/clavulanate for the treatment of acute otitis media treatment failure and recurrent otitis media. Three hundred fifty-four children 6 months-7 years with recurrent otitis media and/or acute otitis media failure were stratified according to age (younger than 2 years versus 2 years or older) and then randomly assigned to 10 days of treatment with gatifloxacin 10 mg/kg once daily or amoxicillin/clavulanate 90 mg/6.4 mg in 2 divided doses. Tympanocentesis was performed in 116 children with acute otitis media treatment failure and 52 with recurrent otitis media at study entry to validate the clinical diagnosis and provide microbiologic data. The primary outcome measure was clinical resolution of infection at the test-of-cure visit 3-10 days after completing treatment. Clinical resolution of acute otitis media was observed in 79.0% (49 of 62) of clinically evaluable children younger than 2 years and 90.3% (56 of 62) of those 2 years or older who were treated with gatifloxacin as compared with 77.6% (45 of 58) of children younger than 2 years and 79.7% (47 of 59) of children 2 years or older treated with amoxicillin/clavulanate. In patients with acute otitis media treatment failure, clinical response rates for children younger than 2 years and those 2 years or older were 87.5% (21 of 24) and 97.0% (32 of 33) with gatifloxacin versus 63.6% (14 of 22) and 83.9% (26 of 31) with amoxicillin/clavulanate. The corresponding clinical response rates in patients with recurrent otitis media were 79.2% (19 of 24) and 85.7% (18 of 21) with gatifloxacin and 90.5% (19 of 21) and 76.0% (19 of 25) with amoxicillin/clavulanate. Clinical success in those subjects having pretreatment middle ear fluid pathogens was similar for the 2 regimens [80.0% (24 of 30) gatifloxacin, 77.1% (27 of 35) amoxicillin/clavulanate]. Emergence of fluoroquinolone-resistant strains was not observed. Both drugs were generally well-tolerated. Diarrhea was the most common drug-related adverse event (10% gatifloxacin, 18% amoxicillin/clavulanate). No evidence of abnormal joint or gait findings was found during a 12-month follow-up. Gatifloxacin once daily is at least as effective and well-tolerated as amoxicillin/clavulanate twice daily in children with acute otitis media treatment failure or recurrent otitis media. There was no evidence of arthrotoxicity or emergence of fluoroquinolone-resistant bacteria in gatifloxacin-treated children.

Infections of the spine in patients with human immunodeficiency virus

Marc Weinstein, MD, Nathan H. Lebwohl, MD, Mark D. Brown, MD, Frank J. Gismont, Miami, FL, USAIntroduction: Infectious diseases in patients with human immunodeficiency virus (HIV) are common and the management of the various bacterial and fungal infections can be a challenge in the immunocompromised host. Skeletal manifestations of patients with HIV have been described in various case reports. Many authors have suggested that spinal infections will occur with greater frequency in the HIV population. However, the incidence and characteristics of spinal infections in these patients have not been reported. The purpose of this study was to evaluate our experience with spinal infections in the HIV population.Methods: The computerized records of all patients discharged with the diagnosis of HIV from our institution from October 1994 through September 2000 were reviewed. Patients with the diagnosis of spinal osteomyelitis, discitis, epidural abscess and tuberculosis were identified, and the charts were examined in detail. In addition to demographic data, the following parameters were recorded: HIV risk factor, admission white blood cell count (WBC), absolute lymphocyte count, erythrocyte sedimentation rate, CD4 count, imaging studies, blood culture results, biopsy results, surgical procedure, antibiotic treatments and duration, length of stay, hospital charges and outcome.Results: For the 6-year period studied, there were 17,717 patient discharges with the diagnosis of HIV. Of these, 17 patients (0.095%) were also treated for a spinal infection. This included eight patients with discitis/osteomyelitis, six patients with tuberculosis (TB) and three patients with an epidural abscess. Of the total number of patients discharged from our institution with these diagnoses, these patients represent 7% of all patients with discitis/osteomyelitis, 35% of patients with spinal TB and 5.5% of patients with epidural abscess. In the eight patients with disc discitis/osteomyelitis, the mean WBC was 8.4, mean absolute lymphocyte count 1,910 and mean CD4 count 339.6. Blood cultures were positive in one of six patients, and a biopsy/surgical specimen was positive in three of six patients. The organism identified in these patients was Staphylococcus aureus (sensitive to oxacillin). The remainder of these patients had positive findings on magnetic resonance imaging or nuclear medicine studies. All eight patients had clinical resolution of infection after 6 to 12 weeks of appropriate antibiotics. In contrast, in the six patients with spinal TB the mean WBC was 10.34, mean absolute lymphocyte count 823 (p=.007) and mean CD4 count 57.2 (p=.003). One of the six patients died during the admission. All were treated with antituberculosis medication protocols. The three patients with epidural abscesses had a mean WBC of 16.17, mean absolute lymphocyte count of 913.3 (p=.007) and mean CD4 count of 20.67 (p=.004). Two of three patients had a computed tomography–guided biopsy. The other was diagnosed by imaging and a positive blood culture. The two biopsies grew Nocardia species, and both of these patients died during the admission. The other patient had Group A streptococcus and was treated with a third-generation intravenous cephalosporin for 6 weeks with clinical improvement. There was no significant difference between the groups with regard to age, gender, race, HIV risk factor or length of hospital stay.Conclusion: Spinal infections in patients with HIV at our institution occur at a rate of 0.095%. This is more than the incidence in the general population but much less then originally suspected. Discitis/osteomyelitis occurs in the HIV patient with a mild to moderate decrease in the CD4 count. These patients would fall into the Center for Disease Control (CDC) class 2 (of 3) classification. The organism identified is consistent with that seen in the general population (S aureus), and the disease responds to appropriate antibiotics. Patients with markedly decreased CD4 counts (CDC class 3) were found to have spinal TB, and patients with the lowest CD4 counts developed epidural abscesses with more malignant species. The three in-hospital deaths occurred in the latter two groups. Although the CD4 count can be used as a predictor of the clinical course of the HIV patient with spinal infection, the identification of the organism still remains paramount in the treatment of this complex patient population.

Cefazolin as empiric therapy in hemodialysis-related infections: Efficacy and blood concentrations

Concern about the increasing incidence of vancomycin-resistant organisms has tempered the enthusiasm for indiscriminate vancomycin use. Cefazolin has an antibacterial activity profile similar to vancomycin against most pathogens encountered in the hemodialysis (HD) population. We evaluated the clinical efficacy and serum concentrations that were achieved during empiric cefazolin use. Fifteen consecutive HD patients (five, conventional HD; five, high-efficiency HD; and five, high-flux HD) with suspected or documented infections warranting antibiotic intervention, including access-related, respiratory tract, urinary tract, or wound infections, were enrolled. Each patient received intravenous cefazolin (20 mg/kg actual body weight rounded to the nearest 500-mg increment [range, 1 to 2 g]) after each dialysis treatment for at least three doses. Cefazolin concentrations were obtained before and immediately after the next three consecutive dialysis treatments. Thirteen patients were evaluated for efficacy and all 15 were evaluated for toxicity and cefazolin blood concentrations. All patients showed at least a short-term (3-week) clinical resolution of infection with cefazolin treatment. No central nervous system toxicities were noted and no other adverse events were expressed by the patients during the course of cefazolin treatment. Predialysis cefazolin concentrations, as determined by high-performance liquid chromatography, were 70.2 +/- 42.7 (conventional HD), 45.6 +/- 18.9 (high-efficiency HD), and 41.6 +/- 23.9 mg/L (high-flux HD) over the three dialysis sessions. Cefazolin at doses of approximately 20 mg/kg administered post-HD appears to be a safe and effective empiric therapy and yields predialysis cefazolin concentrations of 2.5 times or greater than those considered to be the minimum inhibitory concentration breakpoint (16 mg/L) for susceptible organisms. These data support the broader use of cefazolin for empiric treatment in the HD population, allowing vancomycin to be reserved for confirmed resistant organisms. (Am J Kidney Dis 1998 Sep;32(3):410-4)

Persistent acute otitis media

In this three-year prospective study, 137 children with acute otitis media (AOM) that had not responded after one or two empiric antimicrobial treatment courses (termed persistent AOM) underwent tympanocentesis to determine additional antimicrobial therapy based on in vitro susceptibility testing of the bacterial isolate(s). One hundred eleven children with AOM not previously treated are described for comparison. In the persistent AOM group middle ear aspirates grew Streptococcus pneumoniae (24%), Haemophilus influenzae (7%), Brahamella catarrhalis (7%), Streptococcus pyogenes (6%), Staphylococcus aureus (5%), two pathogens (3%) or no bacterial growth (49%); pathogens in previously untreated AOM were similar but fewer patients (30%) had no bacterial growth. After tympanocentesis additional antimicrobial therapy for persistent AOM patients utilizing drugs shown to be effective in vitro against the isolated pathogen failed to produce clinical resolution of infection in 27 (28%) of ears. Differing clinical efficacy was observed with various antimicrobials: amoxicillin (57% failure); trimethoprim/sulfamethoxazole (75% failure); cefaclor (37% failure); cefixime (23% failure); amoxicillin/clavulanate (12% failure); and cefuroxime axetil (13% failure). Presumptive clinical cure for previously untreated AOM patients was similar to that for untreated AOM except for fewer amoxicillin failures (30%). We conclude that clinical failure in persistent AOM occurs (1) even when no pathogen is isolated from tympanocentesis (50% of patients) and (2) despite demonstrated in vitro activity against culture-proved pathogens.

Efficacy of single-agent therapy for the treatment of acute pelvic inflammatory disease with ciprofloxacin

A prospective, randomized, controlled, non-blind clinical trial was conducted to compare the efficacy of monotherapy with ciprofloxacin with that of a combination of clindamycin plus gentamicin in the treatment of patients with acute pelvic inflammatory disease. Pretreatment and post-treatment cervical culture specimens were obtained for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, and Ureaplasma urealyticum. Pretreatment and post-treatment endometrial culture specimens were obtained for those organisms plus facultative and anaerobic bacteria. Minimal inhibitory concentrations were determined on all isolates by agar dilution. Clinical resolution of infection was seen in 31 of 33 (94 percent) ciprofloxacin-treated patients compared with 34 of 35 (97 percent) clindamycin/gentamicin-treated patients. N. gonorrhoeae was eradicated in all cases and C. trachomatis in 12 of 13 cases (92 percent). Ciprofloxacin appeared less effective than clindamycin/gentamicin in eradicating bacterial-vaginosis-associated organisms from post-treatment culture specimens obtained from the endometrium. Comparable clinical response was seen with both regimens. The significance of persistent bacterial-vaginosis-associated organisms following ciprofloxacin therapy is unclear. However, since one goal of treatment of pelvic inflammatory disease should be to eliminate organisms from the upper genital tract, ciprofloxacin may not provide optimal single-agent therapy for pelvic inflammatory disease.