Successful treatment of pneumonia caused by multidrug-resistant Pseudomonas aeruginosa after allogeneic hematopoietic stem cell transplantation with colistin and amikacin inhalation therapy

Pseudomonas aeruginosa is a Gram-negative bacillus that often causes severe infections during immunosuppression in patients with hematologic malignancies. P. aeruginosa can easily acquire drug resistance, and often develops into multidrug-resistant P. aeruginosa (MDRP). Although many antibiotics are used in combination to treat MDRP infections, colistin and amikacin are less likely to be transferred to the lungs, and inhalation therapy may be used. Herein, we report a Case of pneumonia caused by MDRP after allogeneic hematopoietic stem cell transplantation (HSCT) treated with inhaled colistin and amikacin. This 61-year-old female patient was diagnosed with myelodysplastic syndromes and underwent allogeneic HSCT from an 8/8 HLA-matched unrelated donor after reduced-intensity conditioning. On the day of the stem cell infusion, the patient's sputum culture was found to be positive for MDRP. The patient subsequently developed bacteremia, pneumonia, and lung abscess caused by MDRP, and we administered multidrug antibiotic therapy including colistin and amikacin inhalation therapy. The patient's blood cultures were subsequently turned negative, and the lung abscess disappeared. To our knowledge, this is the first case of MDRP pneumonia after HSCT in which colistin and amikacin inhalation therapy was effective.     

Surgical resection for persistent localized pulmonary fungal infection prior to allogeneic hematopoietic stem cell transplantation: Analysis of six cases

ObjectiveAlthough invasive fungal disease (IFD) is an important complication in allogeneic hematopoietic stem cell transplantation (HSCT), the clinical significance of surgery, including the role of surgical resection for persistent pulmonary fungal disease prior to allogeneic HSCT in the current era with a variety of available antifungal agents, is controversial. We investigated the role of surgical resection.MethodsWe retrospectively investigated six patients who underwent surgical resection of suspected pulmonary fungal disease prior to allogeneic HSCT between April 2007 and June 2016 at our medical center.ResultsWe present six patients who underwent surgical resection of suspected pulmonary fungal disease prior to allogeneic HSCT. In our case series, three of four patients who were given a presurgical diagnosis of possible IFD were given a proven diagnosis after surgery, including two cases of invasive aspergillosis (IA) and one case of mucormycosis. All surgeries were performed by video-assisted thoracic surgery (VATS) for lobectomy without major complications. Recurrence of IFD was not observed after allogeneic HSCT in any of the six patients.ConclusionOur experience indicated that surgical resection of persistent localized pulmonary lesions of IFD before allogeneic HSCT was helpful for obtaining a definitive diagnosis and might be useful for reducing recurrence after HSCT.     

Successful neutrophil engraftment supported by granulocyte transfusion in adult allogeneic transplant patients with peri-transplant active infection

Active infection at the time of allogeneic hematopoietic stem cell transplantation (HSCT) is a risk for non-relapse mortality (NRM) after HSCT. Granulocyte transfusion (GTX) has been used to prevent or treat life-threatening infections in patients with severe neutropenia. However, data are limited on the clinical benefits of GTX during HSCT. We retrospectively analyzed the transplant outcomes of HSCT patients who had undergone GTX between 2012 and 2020. Altogether, 20 patients with documented infection had received 55 GTXs during HSCT. No adverse events were observed during the GTX infusion. The average number of granulocytes was 0.40 (range, 0.10–1.59) × 10⁹/kg. The median neutrophil increment one day after GTX was 515 (range, ?6 to 6630)/μl, which was significantly correlated with the infused granulocyte dose (p = 0.0007). A total of 17 of 20 patients achieved neutrophil engraftment. The number of infused granulocytes tended to higher in clinical responders (p = 0.12), and patients receiving ≥ 0.5 × 10⁹/kg showed trend toward to better transplant outcomes (GTX-high vs. GTX-low, 1-year OS; 33% vs. 11%, p = 0.19. 1-year NRM; 44% vs.77%, p = 0.11). The type of red blood sedimenting agents was significantly correlated with the amounts of granulocyte collection. In conclusion, GTX, especially with a high amount of containing granulocytes, could be a safe bridging therapy for neutrophil engraftment after HSCT in patients with active infection.     

Successful treatment of proven coronavirus disease 2019-associated pulmonary aspergillosis with liposomal amphotericin B in a patient with bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is being increasingly recognized as a severe complication that contributes to poor prognoses among patients with COVID-19. However, little is known regarding the clinical course of CAPA with hematological malignancies, especially after allogeneic hematopoietic stem cell transplantation (HSCT). A 29-year-old woman was diagnosed with proven CAPA with an Aspergillus fumigatus identified by cultures of bronchoalveolar lavage and lung biopsy four years after haploidentical HSCT for acute myelogenous leukemia. She had been taking oral prednisolone for bronchiolitis obliterans syndrome that developed after HSCT. Although prolonged RT-PCR positivity for SARS-CoV-2 (133 days after the onset of COVID-19) without shedding of viable virus was observed, the COVID-19 was treated with favipiravir, remdesivir, dexamethasone, and enoxaparin. However, the CAPA did not respond to combination therapy, which included triazole (voriconazole, itraconazole, posaconazole) and echinocandin (caspofungin, micafungin), even though the Aspergillus fumigatus isolate was found to be susceptible to these agents in vitro. Nevertheless, a total of 16 weeks of liposomal amphotericin B (L-AMB) therapy led to a favorable response, and the patient was discharged from the hospital on day 213. This case provided essential experience of CAPA treated with L-AMB in a recipient with chronic respiratory disease after HSCT.     

Long-term extracorporeal photochemotherapy in a pediatric patient with refractory sclerodermatous chronic graft-versus-host disease

Sclerodermatous chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT) in children is difficult to treat and life-threatening. Extracorporeal photochemotherapy (ECP; photopheresis), an immunomodulatory therapy that involves the infusion of autologous peripheral blood leukocytes after ex vivo exposure to the photoactive agent 8-methoxypsoralen and ultraviolet A radiation, is an effective treatment for steroid-refractory cGVHD. After undergoing allogeneic HSCT for pre-B-cell acute lymphoblastic leukemia, a 14-year-old boy developed extensive sclerodermatous cGVHD that was refractory to prednisone, tacrolimus, and sirolimus. ECP was administered over the course of 53 months, during which the skin softened substantially and immunosuppressive therapy was discontinued. This case suggests that long-term ECP is a viable option in children with sclerodermatous cGVHD.     

A fatal case of Exophiala dermatitidis disseminated infection in an allogenic hematopoietic stem cell transplant recipient during micafungin therapy

Exophiala dermatitidis is a dematiaceous fungus that is increasingly becoming the cause of fungal infection in immunocompromised patients. However, the risk factors and optimal treatment modality for E. dermatitidis infection are unknown to date. Herein, we present a fatal case of E. dermatitidis infection in an adult patient that developed after allogeneic hematopoietic stem cell transplantation for chronic active Epstein-Barr virus infection. The dematiaceous fungus caused a breakthrough fungemia despite prophylactic administration of micafungin. Although the patient was intensively treated with liposomal-amphotericin B and voriconazole, serum level of beta-D-glucan continuously increased, and the patient eventually died because of cerebral hemorrhage. An autopsy found multiple involvements of the fungal infection at the bilateral lungs, thoracic cavities, diaphragm, and thyroid. To the best of our knowledge, this is the first reported case of E. dermatitidis infection involving these tissues as determined via autopsy. This case highlights the importance of attention for Exophiala infection in immunocompromised individuals in those given antifungal therapy with echinocandins.     

Fatal Immune Hemolytic Anemia Following Allogeneic Stem Cell Transplantation: Report of 2 Cases and Review of Literature

Immune hemolytic anemia is a well-recognized complication after allogeneic hematopoietic stem cell transplantation (HSCT). There are 4 possible causes for this complication. First, antibodies present in the recipient destroy donor cells. Second, donor red cell antibodies at the time of stem cell infusion are transferred to the recipient. Third, sometimes, engrafted donor lymphocytes cause active production of red cell antibodies. Fourth, another cause of hemolysis after allogeneic HSCT is autoimmune hemolytic anemia (AIHA). It is thought to be due to antibodies produced by the donor’s immune system against antigens on red cells of donor origin. Autoimmune hemolytic anemia after allogeneic HSCT is rare, it is still not well characterized, and it represents a life-threatening situation. We describe 2 patients with acute myeloid leukemia treated with intensive chemotherapy and umbilical cord blood stem cell transplantation (UCBT). One patient developed AIHA at day + 182 and the other at day + 212 after receiving UCBT. Patients received 5 and 7 line treatment options, respectively, including continuous corticosteroids, intravenous immunoglobulin, splenectomy, cyclophosphamide, plasma exchange, rituximab, bortezomib, and eculizumab. However, both patients died because of massive hemolysis after 85 and 106 days of intensive treatment, respectively. These cases reflect the extreme difficulty in the therapeutic management of patients with AIHA following UCBT. After an extensive review of the literature, the exact physiopathologic mechanisms of AIHA after allogeneic HSCT in general, and after UCBT in particular, and therefore an effective treatment remain unknown.     

Hematopoietic stem cell transplantation for HIV cure

The apparent cure of an HIV-infected person following hematopoietic stem cell transplantation (HSCT) from an allogeneic donor homozygous for the ccr5Δ32 mutation has stimulated the search for strategies to eradicate HIV or to induce long-term remission without requiring ongoing antiretroviral therapy. A variety of approaches, including allogeneic HSCT from CCR5-deficient donors and autologous transplantation of genetically modified hematopoietic stem cells, are currently under investigation. This Review covers the experience with HSCT in HIV infection to date and provides a survey of ongoing work in the field. The challenges of developing HSCT for HIV cure in the context of safe, effective, and convenient once-daily antiretroviral therapy are also discussed.     

Serial Plasma Voriconazole Concentrations after Allogeneic Hematopoietic Stem Cell Transplantation

Plasma voriconazole concentrations vary considerably between patients receiving standard dosing, and trough voriconazole concentrations are known to affect efficacy and toxicity. Temporal variations in serial plasma voriconazole concentrations through the course of therapy in hematopoietic stem cell transplantation patients has not been carefully described. Paired voriconazole concentrations in 64 patients were studied to determine the predictability of the second concentration based on the first. The difference between the two values was ≤5% in six patients. In 25 patients, the second concentration was higher by a median of 40%. In 33 patients, the subsequent concentration was lower by a median of 59%. For patients with an initial concentration of <2 μg/ml, the correlation between the two values was poor (r = 0.24; P < 0.17). For those with an initial concentration of ≥2 μg/ml, the correlation was good (r = 0.72; P < 0.0001). There was no relationship between the magnitude of the change and the time elapsing between the two measurements. Among the 43 patients who had an initial concentration of ≥1 μg/ml, the two voriconazole measurements were strongly correlated (r = 0.66, P < 0.0001), but only 67% had a voriconazole serum concentration of ≥1 μg/ml on the second measurement. No studied variables were reliable predictors in identifying concentrations above or below 1 or 2 μg/ml. Our data suggest that variations in voriconazole concentrations are unpredictable despite standard dosing, and the acceptability of a concentration on one occasion cannot be extrapolated to future concentrations in the same patient. This suggests that ongoing therapeutic drug monitoring and dose adjustment may be beneficial in patients requiring prolonged voriconazole therapy.Invasive fungal infections are a significant source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT). Voriconazole, a triazole antifungal agent, is frequently used in the treatment of many yeast and mold infections following HSCT (2, 7). Use of voriconazole for prevention of opportunistic fungal infections has also shown merit (16). Voriconazole is metabolized by the cytochrome P450 isoenzyme system, primarily CYP 3A4, CYP 2C9, and CYP 2C19 (3). Genetic polymorphism of the CYP 2C19 isoenzyme, interactions with several drugs used during the posttransplantation period, self-induced voriconazole metabolism, and direct hepatotoxicity from the conditioning regimen can alter the metabolism and disposition of voriconazole significantly (1, 8). This may increase or decrease voriconazole exposure in an unpredictable fashion, and large inter- and intrapatient variations in voriconazole plasma concentrations have been observed in several reports (11, 12, 14). Recent studies have suggested that there is an association between voriconazole plasma concentrations and successful treatment outcomes, indicating a possible need for therapeutic drug monitoring (TDM) (5, 9, 13).Although the optimum duration of voriconazole prophylaxis and therapy for most fungal infections has not been defined clearly, most allogeneic HSCT recipients require prolonged antifungal therapy—often for several months. Since physiologic (e.g., absorption, metabolism, and protein binding) and pharmacologic (e.g., drug interactions and nonlinear kinetics) conditions change over time following HSCT, plasma voriconazole concentrations would be expected to vary.The temporal variation of plasma voriconazole concentrations through the course of therapy in HSCT patients when measured serially has not been carefully described. We report the results of paired plasma voriconazole measurements in 64 patients following allogeneic HSCT.     

Autoimmune hemolytic anemia (AIHA) following allogeneic hematopoietic stem cell transplantation (HSCT): A retrospective analysis and a proposal of treatment on behalf of the Grupo Español De Trasplante de Medula Osea en Niños (GETMON) and the Grupo Español de Trasplante Hematopoyetico (GETH)

Autoimmune hemolytic anemia (AIHA) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT) associated with poor outcome. However, an optimal therapeutic approach is lacking.Between 2000 and 2015, 4099 allogeneic HSCT were performed in eight pediatric centers of the Grupo Español De Trasplante de Medula Osea en Niños (GETMON) and six adult centers of the Grupo Español de Trasplante Hematopoyetico (GETH). Sixty cases of AIHA were registered with a cumulative incidence of 1.5% occurring at a median of 6 months after HSCT. Patients aged less than 15 years (P = .005), and patients using cord blood (P = .005) or an HLA mismatch donor (P = .005) were more likely to develop AIHA. Most patients were lymphopenic at the time of diagnosis of AIHA, including a low number of regulatory T lymphocytes (median 3/μL).Median lines of treatment received for AIHA was 3 (range, 1-7). Almost all patients received corticosteroids (88%) and more than half received immunoglobulins or rituximab (63% and 67%, respectively). Complete resolution of AIHA was achieved in 33 of 60 cases (55%). Cumulative incidence of AIHA-related mortality was 17 ± 6%. We found a correlation of AIHA outcome with age (better outcome in younger than 15 years, RR = 1.87, P = .01) and rituximab response (higher rate of complete remission in patients responding to rituximab, RR = 1.72, P = .025). We analyzed the factors involved in the response to rituximab and found a better response when there was ABO donor/receptor disparity (P = .014) and in those patients with B lymphocytes count above the median (38/μL) (P = .05).Thirty-six of 60 patients survived yielding a disease free survival of 52±8% at 40 months. In Cox analysis, age (children vs adults, HR: 8.19, CI 95%: 2.39-28.12, P = .001) and AIHA outcome (complete remission vs partial remission/non-response, HR: 4.18, CI 95%: 1.55-11.22, P = .005) were associated with a better survival.Our data suggest that patients who developed AIHA after HSCT are severely lymphopenic and have a high risk of mortality. Outcome is better in children and in patients treated with rituximab. We also propose an algorithm for treatment of AIHA after HSCT.     

Sequential breast implant infections due to Campylobacter fetus subsp. fetus

Campylobacter jejuni and Campylobacter coli are the leading causes of bacterial intestinal infections worldwide, while Campylobacter fetus subsp. fetus (C. fetus) has been reported to cause extraintestinal infections, including medical device implant infections. However, breast implant infections have rarely been reported. We describe the case of a 64-year-old woman with breast implant infection and vertebral osteomyelitis due to C. fetus. The patient recovered by surgical removal of the infected left implant and was treated with antibiotics for 6 weeks. However, two weeks after the completion of antibiotics, she experienced an infection in the right implant due to C. fetus, which had developed quinolone resistance with a G91T mutation during the treatment course. This case showed that C. fetus can cause breast implant infections, and although the infection may appear to be unilateral initially, the possibility of sequential contralateral infection should be considered.     

Calcaneal osteomyelitis due to Achromobacter xylosoxidans: a case report

Achromobacter xylosoxidans (A. xylosoxidans) has been described as an opportunistic pathogen causing infection. The case we describe is that of an elderly man who had osteomyelitis of calcaneal bone caused by A. xylosoxidans. As far as we are aware there are only 5 cases of osteomyelitis with A. xylosoxidans in the literature. Impaired defensive mechanism of the foot in direct contact with this waterborne bacterium can cause this disease. Because of the high level of antibiotic resistance of this bacterium, clinically more attention should be paid to patients who have impaired defensive mechanisms in their extremities, for example free flaps.     

Soft tissue infection caused by Mycolicibacter kumamotonensis

Mycolicibacter kumamotonensis (M. kumamotonensis), formerly Mycobacterium kumamotonense, is a nontuberculous mycobacteria species, which was first separated from Mycobacterium terrae complex in 2006. Reports about infections caused by M. kumamotonensis are extremely rare, with most of them being lung infection. Here, we report the case of a 68-year-old man with a hobby of gardening who developed swelling in his right middle finger. He underwent surgical debridement at a previous hospital and was diagnosed with nontuberculous mycobacteria infection based on positive findings of acid-fast staining of pus obtained from the surgical specimen. He was treated with rifampicin, ethambutol, and clarithromycin, but the swelling worsened. Therefore, he was referred to our hospital for further examination and treatment. We performed a second debridement and added isoniazid to the treatment regimen, but the swelling continued to worsen. We then administered levofloxacin, but his condition did not change. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry and DNA sequencing analysis confirmed M. kumamotonensis as the causative bacterium. Since the finger swelling did not improve, the patient underwent a third debridement and amikacin was added to the treatment regimen. Finally, the infection was controlled. He completed amikacin therapy and will continue treatment with the other five antibiotics for a total of 24 months. To the best of our knowledge, this is the first report of a patient with M. kumamotonensis soft tissue infection. We consider this case might provide important insights into the diagnosis and treatment of soft tissue infections caused by M. kumamotonensis.     

Safety of percutaneous dilational tracheostomy in hematopoietic stem cell transplantation recipients requiring long-term mechanical ventilation

Purpose

Recent reports have shown that the outcome of mechanically ventilated patients after hematopoietic stem cell transplantation (HSCT) has improved. This study was conducted to clarify if percutaneous dilational tracheostomy is safe in this group of patients and to report the outcome of HSCT recipients requiring long-term mechanical ventilation.

Methods

A retrospective review of our 8-year experience with patients with acute respiratory insufficiency after HSCT, requiring long-term mechanical ventilation and percutaneous dilational tracheostomy and an analysis of patient outcomes were made.

Results

Percutaneous dilational tracheostomy was safely performed in all 51 patients. Although 1 patient (2%) developed a pneumothorax that required drainage, stoma infections or severe bleeding complications were not observed. Of the 51 patients in the study, 14 (27%) survived the intensive care unit stay, and 10 of them were ventilated for more than 20 days. The intensive care unit survival rate for the period from 1998 to 2001 was 11% compared with 38% for the period from 2002 to 2005 (P = .053).

Conclusions

Percutaneous dilational tracheostomy can be safely performed on patients with acute respiratory failure after HSCT. This procedure did not result in postoperative wound infections or significant bleeding complications. Furthermore, the results of our study indicate that today even patients with prolonged mechanical ventilation (>20 days) have a chance of long-term survival.     

Mediastinitis superinfected by Achromobacter xylosoxidans. A case report

We describe an extremely rare case of mediastinitis superinfected by emerging Achromobacter xylosoxidans. After mitral and aortic valves replacement, the patient first developed a Staphylococcus aureus mediastinitis, and five days after starting adapted antibiotic therapy, superficial pus analysis revealed the presence of Achromobacter xylosoxidans. This superinfection was considered superficial and focus was made on Staphylococcus aureus mediastinitis. Three weeks later, no more Staphylococcus aureus was found in pus samples and the sepsis seemed under control. Unfortunately, blood cultures were again positive for Achromobacter xylosoxidans three weeks later and the patient died from septic shock.     

Hemophagocytic syndrome with severe sepsis caused by Capnocytophaga canimorsus

Capnocytophaga canimorsus, commonly transmitted by dog bites, can cause severe sepsis, and the mortality rate is very high. We experienced a case of hemophagocytic lymphohistiocytosis (HLH) complicated by severe sepsis caused by C. canimorsus. A 58-year-old man with no remarkable medical history was admitted to another hospital with fever and mild consciousness disorder developed 3 days after being bitten by his dog. The next day, the patient developed disseminated intravascular coagulation and shock and was transferred to our emergency medical center. Blood tests showed hyperferritinemia and cytopenia, and bone marrow aspiration was performed. As a result, we diagnosed severe sepsis and HLH. Once antibiotic and steroid therapy was started, the patient's infection and cytopenia improved. Unfortunately, the patient's fingers and toes required amputation, but his life was saved, and he was discharged from hospital. Because HLH may be hidden in such cases, it may be necessary to measure serum ferritin and perform bone marrow aspiration if hyperferritinemia is suspected.     

Helicobacter cinaedi kidney cyst infection and bacteremia in a patient with autosomal dominant polycystic kidney disease

A 48-year-old man with autosomal dominant polycystic kidney disease (ADPKD) was admitted to our hospital with a 5-day history of lower right back pain, high-grade fever, and arthralgia. He was diagnosed with right kidney cyst infection and bacteremia due to Helicobacter cinaedi (H. cinaedi) based on these symptoms, highly elevated CRP (32.25 mg/dL), abdominal magnetic resonance imaging findings, and the identification of H. cinaedi from blood cultures using PCR and sequence analysis of the 16S ribosomal DNA gene. Intravenous cefotaxime 0.5 g twice daily followed by meropenem 0.5 g twice daily and ciprofloxacin 200 mg twice daily were partially effective; oral doxycycline added at 200 mg/day finally eradicated the infection. Total duration of antimicrobial therapy was 9 weeks. H. cinaedi infections typically present as bacteremia with or without cellulitis in immunocompromised patients such as those with AIDS or malignant disease. To our knowledge, this is the first report describing an ADPKD patient with H. cinaedi cyst infection. Although H. cinaedi infections are increasingly recognized, even in immunocompetent subjects, numerous cases may still be overlooked given that this bacterium is slow-growing, and is difficult to culture, be Gram-stained, and identify on phenotypic tests. Consideration of this bacterium as a possible pathogen and sufficient duration of incubation with molecular testing are necessary in treating ADPKD patients with cyst infection.     

A case of facial cellulitis caused by group B streptococcus in an extremely low birthweight infant

Group B streptococcus (GBS) is an important pathogen that causes neonatal sepsis and meningitis, which have high mortality and morbidity. Cellulitis is a rare presentation of late-onset neonatal GBS infection. We report the case of an extremely low birthweight infant with facial cellulitis caused by late-onset GBS infection. A 590-g male neonate was delivered by Cesarean section at 23 gestational weeks due to intrauterine GBS infection. Although he was effectively treated with 2 weeks of antimicrobial therapy for early-onset GBS sepsis, he subsequently developed facial and submandibular cellulitis caused by GBS at 44 days of age. He was treated with debridement and antibiotic therapy, and after 2 months his facial involvement had improved, but cosmetic issues remained. Neonatal GBS infection requires a prompt sepsis workup followed by the initiation of empiric antibiotic therapy. Additionally, lifesaving surgical debridement is sometimes necessary for cellulitis, even in premature infants.     

Preseptal cellulitis with Streptococcus pyogenes complicated by streptococcal toxic shock syndrome: A case report and review of literature

Preseptal cellulitis, an infection of the eyelid and skin around the eye, can be distinguished from orbital cellulitis. It is common in children and is rarely complicated. Streptococcus pyogenes is one of the major pathogens causing preseptal cellulitis. Here, we report a case of a 46-year-old man with carcinoma of unknown primary presenting preseptal cellulitis of S. pyogenes complicated by streptococcal toxic shock syndrome and multiple metastatic abscesses involving right eyelid, subcutaneous tissue in the scalp, mediastinum, bilateral pleural spaces, pericardial space, and the left knee. Although he required a prolonged hospitalization, antibiotic therapy and multiple courses of debridement led to full recovery. A literature review revealed that there were only four cases of preseptal cellulitis with S. pyogenes in adults and two cases were complicated by streptococcal toxic shock syndrome. The cases had either trauma or immunocompromising factors similar to our patient. All patients survived with antibiotic therapy and debridement, and the functional outcome was favorable. In summary, preseptal cellulitis caused by S. pyogenes can be severe in adult cases where immunocompromising factors and type of strain may play a role in the severity of the disease. Awareness of the risk of severe complications, treatment with appropriate antibiotic therapy, and timely debridement are crucial for favorable prognoses.     

Characterization of Bacterial Infections in Allogeneic Hematopoietic Stem Cell Transplant Recipients Who Received Prophylactic Levofloxacin With Either Penicillin or Doxycycline

OBJECTIVE: To describe the effect of a combination prophylactic regimen of levofloxacin, a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class, with either penicillin or doxycycline on the changing epidemiology of bacterial infections and antimicrobial resistance patterns of isolated organisms in the allogeneic hematopoietic stem cell transplant (HSCT) patient population.PATIENTS AND METHODS: We conducted a single-center, retrospective cohort study of all allogeneic HSCT recipients from January 1, 2003, through August 31, 2008, who received prophylactic levofloxacin in combination with penicillin (or with doxycycline in penicillin-allergic patients) from allogeneic stem cell infusion until neutrophil engraftment.RESULTS: Of the 258 patients who underwent allogeneic HSCT during the study period, 231 received levofloxacin prophylaxis, 76 (33%) of whom developed an infection within 3 months after transplant. Over time, the ratio of gram-positive to gram-negative (GN) infections decreased from 2.11 in 2004, the first year that GN organisms were isolated, to 1.11 in 2008 (P=.20). Emergence of fluoroquinolone-resistant GN bacteria was observed (P=.02), whereas resistance to extended-spectrum β-lactams did not change over time. Combined vancomycin-resistant enterococci colonization and infection rates increased during the study period (P=.04). Clostridium difficile colitis was uncommon.CONCLUSION: Levofloxacin with penicillin or doxycycline prophylaxis may contribute to the emergence of resistant GN infections in allogeneic HSCT recipients over time. Our findings provide additional support for the current standard of practice of administering empiric monotherapy with an antipseudomonal β-lactam if these patients develop fever or are suspected to have an infection.BAL = bronchoalveolar lavage; CoNS = coagulase-negative staphylococci; GN = gram-negative; GP = gram-positive; HSCT = hematopoietic stem cell transplant; MDR = multidrug-resistant; VRE = vancomycin-resistant enterococciThe utility of prophylactic antibiotics during the period of chemotherapy-induced neutropenia has been a source of controversy for decades. Reductions in gram-negative (GN) bacteremia, febrile episodes, and hospitalizations have been documented with the use of a prophylactic regimen.^1-6 Newer fluoroquinolones, particularly levofloxacin, have emerged as preferred agents because of their potent activity against GN bacteria, enhanced gram-positive (GP) coverage, excellent oral bioavailability, and favorable patient tolerance. Historically, the National Comprehensive Cancer Network, the Centers for Disease Control and Prevention, and the Infectious Diseases Society of America have offered conflicting recommendations regarding the use of a prophylactic antibiotic regimen after allogeneic hematopoietic stem cell transplant (HSCT).^7-9 Although this patient population is at high risk of fever and subsequent infection during the neutropenic period, a reduction in infection-related mortality rates has not been clearly demonstrated, and emergence of multidrug-resistant (MDR) organisms has remained a concern. Recently, the American Society for Blood and Marrow Transplantation endorsed fluoroquinolone prophylaxis if neutropenia is anticipated for 7 days or more, again emphasizing the risk of perpetuating fluoroquinolone-resistant bacteria.¹⁰Infections caused by MDR organisms are associated with increased mortality, hospital length of stay, and health care costs.¹¹ Given these concerns, the Infectious Diseases Society of America suggests that, if a prophylactic regimen is used in asymptomatic, afebrile, neutropenic patients, hospital and HSCT center antibiotic-susceptibility profiles should be reviewed routinely.⁸ In allogeneic HSCT recipients, the patient population at highest risk of developing infection during the period of neutropenia, the effect of fluoroquinolone prophylaxis on infections over time has not been adequately described, nor is there adequate information identifying the evolution of resistance patterns of those organisms isolated.Since 1998, levofloxacin has been used with penicillin (or doxycycline for penicillin-allergic patients) at Mayo Clinic in Rochester, MN, as prophylaxis during the neutropenic period after HSCT. This study aimed to evaluate the impact of this prophylactic regimen on the etiology and resistance profiles of organisms implicated in infection during the first 3 months after allogeneic HSCT. Also of interest was the incidence of Clostridium difficile colitis and vancomycin-resistant enterococci (VRE) colonization and infection in this patient population.