The cintent of reseach paper

Acinetobacter species are a group of bacterial microorganisms, gram-negative coccobacillus^1,2). Acinetobacter infections have attracted increasing attention in recent years because they are resistant to most antibiotics and can be found in both hospitalized patients and the community¹⁾. Among those, A. baumannii mainly infects patients with impaired host defense, such as those who are in intensive care units, therefore A. baumannii infection is associated with increased mortality^3-5). Furthermore, sepsis is the leading cause of direct maternal and fetal morbidity and mortality⁶⁾. However, there are a few reports of outcomes of Acinetobacter infection during pregnancy and puerperium^1,7). Moreover, there are no reports of septic shock due to A. lwoffii infection during pregnancy. In this report, we present a case of septic shock due to A. lwoffii infection in the 31st week of gestation.

A 47-year-old, gravida 2, para 1 (cesarean section due to placenta previa) woman had undergone a prenatal checkup at a previous hospital. Her past medical history was unremarkable. She was diagnosed with gestational diabetes at 12 weeks of gestation and was started on insulin self-injection. Her blood hemoglobin A1c (HbA1c) level was 5.9%. Glycemic control was appropriate after starting insulin, with blood HbA1c ranging from 5.6% at 19 weeks of gestation to 5.5% at 25 weeks of gestation. At 28 weeks of gestation, she was admitted to the hospital with a diagnosis of threatened premature labor due to a shortened cervix (length: 17 mm) and was started on intravenous magnesium preparations. At 31 weeks and one day of gestation, she developed a fever of 38.5°C. Laboratory findings showed an elevated white blood cell (WBC) count of 14,700 /µL and a C-reactive protein (CRP) level of 8.9 mg/dL. She was started on tazobactam/piperacillin (TAZ/PIPC) 13.5 g/day. Her percutaneous oxygen saturation (SpO₂) dropped to 90%, and oxygen administration was started (mask 5 L/min). Two days later, laboratory tests showed a WBC count of 11,400 /µL, CRP level of 14.2 mg/dL, and procalcitonin level of 16 ng/mL. A urinary tract infection was suspected because she had grossly cloudy urine and a transabdominal ultrasound showed a dilated right renal pelvis. Her antibiotic dosage was elevated to TAZ/PIPC 18 g/day. At 31 weeks and 4 days of gestation, her body temperature increased to 40°C, her systolic blood pressure had dropped to the 70-mmHg range, and laboratory tests showed a WBC count of 18,200 /µL, CRP level of 28.8 mg/dL, and thrombocytopenia (platelet count: 14×10⁴/µL). Two sets of blood cultures were performed, and gram-negative rods were detected in both. The urine culture did not detect any organisms. She was diagnosed with septic shock and associated disseminated intravascular coagulation, and transferred to our hospital. Rapid antigen tests at the previous hospital for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Group A Streptococcus, and influenza virus were negative.

Chest radiography and contrast-enhanced computed tomography (CT) imaging on arrival at our hospital revealed infiltrating and frosted shadows in the lower and upper lobes of the right lung (Figure 1), and a pleural effusion, leading to the diagnosis of severe bacterial pneumonia. There was no evidence of urinary tract infection, such as dilated renal pelvis on CT or loin pain. The fetal heart rate baseline on cardiotocogram (CTG) was around 100/min, with frequent bradycardia of 80-90 bpm appearing about once a minute (Figure 2). With a diagnosis of non-reassuring fetal status (NRFS), an emergency cesarean section was performed on the same day. The newborn was male with a birthweight of 1,788 g, and 1-minute and 5-minute Apgar scores of 5 and 7, respectively. The umbilical arterial pH was 7.247 with a base excess of −5.20. The newborn was given an artificial surfactant with a diagnosis of respiratory distress syndrome. Culture specimens from blood, sputum, nasal mucus, skin, ear discharge, and anus were collected on the day of birth, but no causative organisms were detected in any of them.

The patient was intubated and admitted to the intensive care unit (ICU) postoperatively. Postoperative antibiotics were meropenem (MEPM) 3 g/day and azithromycin (AZM) 500 mg/day. On the first postoperative day (POD 1), laboratory findings showed a WBC count of 19,000 /µL and a CRP level of 30.1 mg/dL. On the POD 3, A. lwoffii was detected in two sets of blood cultures collected at the previous hospital. The antibiotic susceptibility findings of the blood culture isolates are shown in Table 1. As the results confirmed that the isolate was sensitive to MEPM, the patient was continued on MEPM, and AZM was discontinued. Laboratory findings showed an improvement in the inflammatory response over time, and the chest radiography showed improvement in the pneumonia. Oxygen administration was discontinued on POD 8. Laboratory findings showed a decrease in the WBC count to 5,600 /µL and CRP level to 0.62 mg/dL, and MEPM administration was discontinued on POD 10. She was discharged on POD 13. Blood cultures taken on POD 5, and vaginal cultures taken on POD 10 did not detect any pathogenic bacteria. Histopathology of the placenta revealed neutrophil infiltration of the chorioallantois membrane, and the patient was diagnosed with chorioamnionitis (CAM). On the other hand, no Gram-negative coccus was detected in the placental tissue, indicating placental infection with A. lwoffii. The patient’s clinical course is summarized in Figure 3.

Informed consent was obtained from the patient for the publication of her case details.

Fig. 1-1. Imaging on arrival at our hospital (Chest radiography)

→:infiltrating and frosted shadow

Fig. 1-2. Imaging on arrival at our hospital (contrast-enhanced computed tomography)

A→:infiltrating and frosted shadow, B→: pleural effusion

Fig. 2. Fetal cardiotocogram (CTG) on arrival at out hospita

Table 1. Antibiotic susceptibility of the Acinetobacter lwoffii isolate grown in blood culture

(Abbreviations)

ABPC, ampicillin;AMK, amikacin;AZT, azidothymidine;CAZ, ceftazidime;CCL, cefaclor;CEZ, cefazolin;CFPN, cefcapene;CL, colistin;CPZ, chlorpromazine;CTM, ceftizoxime;CTRX, ceftriaxone;CTX, ceftriaxone;FMOX, flomoxef;FOM, fosfomycin;GM, gentamicin;I:intermediate, IPM, imipenem;LVFX, levofloxacin;MIC, minimal inhibitory concentration;MEPM, meropenem;MINO, minocycline;NA:not available, N/R:not reported;PIPC, piperacillin;S:susceptible;SBT, sulbactam;ST, streptomycin;TOB, tobramycin.

Fig. 3. Summary of the patient’s clinical course

(Abbreviations)

A. lwoffii, Acinetobacter lwoffii; AZM, azithromycin; C/S, cesarean section; CRP, C-reactive protein; MEPM, meropenem; PIPC, piperacillin; POD, postoperative day; TAZ, tazobactam; WBC, white blood cell.

More than 30 different Acinetobacter species have been identified¹⁾. Among them, A. baumannii tends to be resistant to multiple antibiotics³⁾. This antibiotic resistance has led to an increasing number of reports of associated morbidity and mortality worldwide¹⁾. Most Acinetobacter infections occur in individuals with some form of impaired immunity.

There are a limited number of reports on the clinical outcome of Acinetobacter infection in pregnancy. Aivazova et al.⁷⁾ reported a case of a vaginal A. baumannii infection during pregnancy and puerperium. The patient had CAM and contractions; therefore, a cesarean section was performed. In that case, A. baumannii was only detected from cervical swabs and not from amniotic fluid or blood. Therefore, the authors concluded that Acinetobacter may have been a colonizer rather than the true cause of infection. He et al.¹⁾ also determined perinatal and pregnancy outcomes of A. baumannii infection. They reviewed a total of 40 bacterial cultures positive for A. baumannii over a five-year period, consisting of 33 maternal cultures, 3 neonatal cultures, and 4 autopsy cultures. Lochia was the most common sample source (16/40, 40%), followed by wound (13/40, 32.5%), and others (breast milk, lung aspiration catheter tip, throat, sputum, tracheal aspiration, and blood from a central line). Adverse pregnancy outcomes, including CAM, spontaneous abortion, and preterm labor were seen in all pregnancies with positive A. baumannii cultures (including non-sterile sites) around the time of labor. The authors concluded that A. baumannii could lead to premature contractions and be associated with CAM during pregnancy.

A. lwoffii is a commensal organism of the human skin, oropharynx, perineum, and urinary tract⁸⁾. Compared to A. baumannii infection, there have been few reports of A. lwoffii infection⁹⁾. Ku et al.⁸⁾ conducted a retrospective study of the clinical features of A. lwoffii bacteremia. They reviewed 18 cases of confirmed A. lwoffii bacteremia in patients whose underlying conditions included cancer (11/18 patients), systemic lupus erythematosus (1/18 patients), chronic obstructive pulmonary disease (2/18 patients) and other diseases (4/18 patients)⁹⁾. They showed that indwelling catheter-related A. lwoffii bacteremia in immunocompromised individuals is associated with a low risk of mortality if the catheter is removed and appropriate antimicrobial therapy is administered⁸⁾. In contrast, multidrug-resistant A. lwoffii is emerging as a pathogen in neonatal sepsis. Mittal et al.¹⁰⁾ evaluated the clinical characteristics and antibiotic susceptibility profile of A. lwoffii in cases of neonatal sepsis. They concluded that the incidence of multidrug-resistant A. lwoffii infection is increasing, particularly in premature and very low birth-weight neonates, and that it is important to use antibiotics judiciously and timeously¹⁰⁾.

Although septic shock is rare in pregnancy, occurring in 0.002-0.01% of all deliveries, it leads to a high rate of preterm delivery and perinatal death¹¹⁾. The maternal mortality rate among pregnant women with septic shock is 20-28%, and 3.6% of pregnant women diagnosed with sepsis before delivery experience an intrauterine fetal death^11,12). Acute pyelonephritis is the most common cause of septic shock in pregnant women, and Escherichia coli is the most common causative organism¹³⁾. Several risk factors for maternal septic shock have been identified, including vaginal discharge, history of pelvic infection, history of Group B Streptococcus infection, multiple pregnancy, assisted reproduction, amniocentesis, cervical cerclage, prolonged spontaneous rupture of membranes, cesarean section, vaginal trauma, wound hematoma, and retained products of conception as obstetric factors; and obesity, impaired glucose tolerance or diabetes, impaired immunity, immunosuppressant medication, maternal age over 35 years, Group A Streptococcus infection in close contacts and family members, and medical conditions (malaria, hepatitis, HIV infection, sickle cell disease) as non-obstetric factors¹⁴⁾. As the fetal consequences of maternal sepsis are related primarily to vascular changes and poor fetal perfusion, CTG, doppler flowmetry, and umbilical artery doppler assessment are useful for assessing fetal well-being¹⁵⁾. However, in the presence of CAM and NRFS, delivery should be expedited as a source control measure, regardless of the gestational age¹⁶⁾. Pregnancy represents an immunocompromised state created in order not to reject the growing fetus, which predisposes the mother to infection¹⁷⁾. Additionally, respiratory infections in pregnancy are more likely to be severe because the diaphragm is elevated by the pregnant uterus¹⁸⁾.

In our case, the patient had no underlying medical conditions that made her susceptible to infection and no immunosuppressive drug use. Nevertheless, in addition to changes in the immune system and physiology associated with pregnancy, pregnancy at an advanced maternal age, and the patient's susceptibility to infection due to gestational diabetes may have led to severe pneumonia caused by nosocomial infection. Although it is unlikely that the A. lwoffii isolate was multidrug-resistant, based on the antibiotic susceptibility findings of the blood culture isolates, these factors may have contributed to the pneumonia. As sputum cultures were not collected and bacteria were detected only from blood cultures, the pneumonia may have been secondary to a bloodstream infection acquired by a nonrespiratory portal of entry. As no bacteria were detected in the urine culture, it is unlikely that the route of entry was the urinary tract. Furthermore, none of the cultures of samples collected from the neonate were positive for A. lwoffii or any other pathogens. Therefore, the delivery may have occurred before the infection spread from the amniotic fluid to the fetus. Because the patient was already suffering from NRFS due to shock at the time of transport to our hospital, this suggests that prompt delivery may have prevented severe infection of the fetus. Furthermore, the early initiation of appropriate antibiotics may also have contributed to preventing infection of the fetus.

In conclusion, this case shows that pregnant women without underlying medical conditions may develop nosocomial infections due to reduced immunity caused by pregnancy or gestational diabetes, and that this can lead to septic shock, CAM, and NRFS. Therefore, to improve the clinical outcome, antibiotic therapy should be initiated without delay and delivery should be expedited.

We have no conflict of interest with regard to our case report.